Furfural from Pine Needle Extract Inhibits the Growth of a Plant Pathogenic Fungus, Alternaria mali

PubMed Central

Yoo, Sun Kyun; Moon, Sung-Kwon; Lee, Ung-Soo

2007-01-01

The antifungal effect of pine needle extract prepared by a distinguishable extraction method and the dry distillation method, was examined. The effect of this extract itself was insignificant. The chemical components of pine needle extract were then investigated by gas chromatographic analysis, and four chemical components, acetol, furfural, 5-methyl furfural, and terpine-4-ol, were identified. The antifungal effects of those four chemical components against Alternaria mali (A. mali), an agent of Alternaria blotch of apple, were then examined. It was observed that the minimum inhibitory concentrations (MICs) were 6.25, 0.78, 0.78, and 12.5 (mg/ml) of acetol, furfural, 5-methyl furfural, and terpine-4-ol, respectively. MICs of furfural and 5-methyl furfural had the same order of magnitude as that of an antifungal agrochemical, chlorothalonil. Although furfural itself can not be completely substituted for an antifungal agrochemical, a partial mixture of furfural and antifungal agrochemical may be used as a substitute. The use of agrochemicals for the prevention of plant disease caused by pathogenic fungus such as A. mali could be partially reduced by the application of this mixture. PMID:24015067

Risk assessment for the spread of Candida sp. in dental chair unit waterlines using molecular techniques.

PubMed

Mazari, Wissame; Boucherit-Otmani, Zahia; El Haci, Imad Abdelhamid; Ilahi, Amine; Boucherit, Kebir

2018-05-04

The aim of this study was to evaluate the presence of yeasts in dental chair unit waterlines (DCUWLs) and to test their ability to form biofilms. Eighteen dental waterlines were analysed by culture in liquid Sabouraud in order to allow the quantification and the purification of isolated yeasts from their internal surfaces. All isolates were identified by standard laboratory procedures, including CHROMagar Candida medium for orientation, commercial yeast identification system Api Candida, MALDI-TOF MS and DNA sequencing. To evaluate their kinetics of antifungal susceptibility during different phases of biofilm formation, these yeasts were subjected to three antifungal agents. From the 18 DCUWLs studied, 10 were altered (55.56%). Eleven strains of Candida sp. [Candida albicans (2), Candida guilliermondii (5) and Candida glabrata (4)] and two species of non-Candida; Rhodotorula spp. (1) and Trichosporon spp. (2) were identified. The majority of yeasts in planktonic form were susceptible to amphotericin B, caspofungin and voriconazole, except C. albicans was resistant to voriconazole. In the biofilm form, caspofungin was the most effective antifungal agent for all isolated strains. For the other antifungal agents, sessile cells were resistant. Several types of yeasts were identified; the most frequently isolated genus was Candida. The majority of these yeasts had the ability to form biofilms and resisted antifungal agents used in this study. © 2018 FDI World Dental Federation.

Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi

PubMed Central

Pinheiro, Ana M.; Carreira, Alexandra; Prescott, Thomas A. K.; Ferreira, Ricardo B.; Monteiro, Sara A.

2017-01-01

The lack of antifungal drugs with novel modes of action reaching the clinic is a serious concern. Recently a novel antifungal protein referred to as Blad-containing oligomer (BCO) has received regulatory approval as an agricultural antifungal agent. Interestingly its spectrum of antifungal activity includes human pathogens such as Candida albicans, however, its mode of action has yet to be elucidated. Here we demonstrate that BCO exerts its antifungal activity through inhibition of metal ion homeostasis which results in apoptotic cell death in C. albicans. HIP HOP profiling in Saccharomyces cerevisiae using a panel of signature strains that are characteristic for common modes of action identified hypersensitivity in yeast lacking the iron-dependent transcription factor Aft1 suggesting restricted iron uptake as a mode of action. Furthermore, global transcriptome profiling in C. albicans also identified disruption of metal ion homeostasis as a potential mode of action. Experiments were carried out to assess the effect of divalent metal ions on the antifungal activity of BCO revealing that BCO activity is antagonized by metal ions such as Mn2+, Zn2+, and Fe2+. The transcriptome profile also implicated sterol synthesis as a possible secondary mode of action which was subsequently confirmed in sterol synthesis assays in C. albicans. Animal models for toxicity showed that BCO is generally well tolerated and presents a promising safety profile as a topical applied agent. Given its potent broad spectrum antifungal activity and novel multitarget mode of action, we propose BCO as a promising new antifungal agent for the topical treatment of fungal infections. PMID:28702011

Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi.

PubMed

Pinheiro, Ana M; Carreira, Alexandra; Prescott, Thomas A K; Ferreira, Ricardo B; Monteiro, Sara A

2017-01-01

The lack of antifungal drugs with novel modes of action reaching the clinic is a serious concern. Recently a novel antifungal protein referred to as Blad-containing oligomer (BCO) has received regulatory approval as an agricultural antifungal agent. Interestingly its spectrum of antifungal activity includes human pathogens such as Candida albicans , however, its mode of action has yet to be elucidated. Here we demonstrate that BCO exerts its antifungal activity through inhibition of metal ion homeostasis which results in apoptotic cell death in C. albicans . HIP HOP profiling in Saccharomyces cerevisiae using a panel of signature strains that are characteristic for common modes of action identified hypersensitivity in yeast lacking the iron-dependent transcription factor Aft1 suggesting restricted iron uptake as a mode of action. Furthermore, global transcriptome profiling in C. albicans also identified disruption of metal ion homeostasis as a potential mode of action. Experiments were carried out to assess the effect of divalent metal ions on the antifungal activity of BCO revealing that BCO activity is antagonized by metal ions such as Mn 2+ , Zn 2+ , and Fe 2+ . The transcriptome profile also implicated sterol synthesis as a possible secondary mode of action which was subsequently confirmed in sterol synthesis assays in C. albicans . Animal models for toxicity showed that BCO is generally well tolerated and presents a promising safety profile as a topical applied agent. Given its potent broad spectrum antifungal activity and novel multitarget mode of action, we propose BCO as a promising new antifungal agent for the topical treatment of fungal infections.

Diffusible and Volatile Antifungal Compounds Produced by an Antagonistic Bacillus velezensis G341 against Various Phytopathogenic Fungi.

PubMed

Lim, Seong Mi; Yoon, Mi-Young; Choi, Gyung Ja; Choi, Yong Ho; Jang, Kyoung Soo; Shin, Teak Soo; Park, Hae Woong; Yu, Nan Hee; Kim, Young Ho; Kim, Jin-Cheol

2017-10-01

The aim of this study was to identify volatile and agar-diffusible antifungal metabolites produced by Bacillus sp. G341 with strong antifungal activity against various phytopathogenic fungi. Strain G341 isolated from four-year-old roots of Korean ginseng with rot symptoms was identified as Bacillus velezensis based on 16S rDNA and gyrA sequences. Strain G341 inhibited mycelial growth of all phytopathogenic fungi tested. In vivo experiment results revealed that n -butanol extract of fermentation broth effectively controlled the development of rice sheath blight, tomato gray mold, tomato late blight, wheat leaf rust, barley powdery mildew, and red pepper anthracnose. Two antifungal compounds were isolated from strain G341 and identified as bacillomycin L and fengycin A by MS/MS analysis. Moreover, volatile compounds emitted from strain G341 were found to be able to inhibit mycelial growth of various phytopathogenic fungi. Based on volatile compound profiles of strain G341 obtained through headspace collection and analysis on GC-MS, dimethylsulfoxide, 1-butanol, and 3-hydroxy-2-butanone (acetoin) were identified. Taken together, these results suggest that B. valezensis G341 can be used as a biocontrol agent for various plant diseases caused by phytopathogenic fungi.

Antifungal Properties of Crude Extracts, Fractions, and Purified Compounds from Bark of Curatella americana L. (Dilleniaceae) against Candida Species

PubMed Central

Mendes de Toledo, Cleyton Eduardo; Santos, Patrícia Regina; Palazzo de Mello, João Carlos; Dias Filho, Benedito Prado; Ueda-Nakamura, Tânia

2015-01-01

The ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian cerrado, in which crude extract showed antifungal activity in a preliminary study. In this work, the antifungal and cytotoxic properties of the crude extract, fractions, and isolated compounds from C. americana were evaluated against the standard yeast strains Candida albicans, C. tropicalis, and C. parapsilosis, clinical isolates, and fluconazole-resistant strains. The combinatory effects between subfractions and isolated compounds and effects on cell morphology, virulence factors, and exogenous ergosterol were also evaluated. The MIC obtained against the Candida species including fluconazole-resistant strain ranged from 15.3 to 31.3 µg/mL for crude extract, 3.9 to 15.6 µg/mL for ethyl acetate fraction, and 7.8 to 31.3 µg/mL for subfractions. The isolated compounds identified as 4′-O-methyl-catechin, epicatechin-3-O-gallate, and 4′-O-methyl-catechin-3-O-gallate showed lower antifungal activity than the crude extract and fractions (MIC ranging from 31.3 to 125.0 µg/mL). The addition of exogenous ergosterol to yeast culture did not interfere in the antifungal activity of the extract and its fractions. Synergistic antifungal activity was observed between subfractions and isolated compounds. The effects on virulence factors and the different mechanisms of action compared to fluconazole and nystatin suggest that this ethnomedicinal plant may be an effective alternative treatment for candidiasis. PMID:26347790

Antifungal activities of the essential oils in Syzygium aromaticum (L.) Merr. Et Perry and Leptospermum petersonii Bailey and their constituents against various dermatophytes.

PubMed

Park, Mi-Jin; Gwak, Ki-Seob; Yang, In; Choi, Won-Sil; Jo, Hyun-Jin; Chang, Je-Won; Jeung, Eui-Bae; Choi, In-Gyu

2007-10-01

This study was carried out in order to investigate the potential of using plant oils derived from Leptospermum petersonii Bailey and Syzygium aromaticum L. Merr. Et Perry as natural antifungal agents. The antifungal effects of essential oils at concentrations of 0.05, 0.1, 0.15, and 0.2 mg/ml on the dermatophytes Microsporum canis (KCTC 6591), Trichophyton mentagrophytes (KCTC 6077), Trichophyton rubrum (KCCM 60443), Epidermophyton floccosum (KCCM 11667), and Microsporum gypseum were evaluated using the agar diffusion method. The major constituents of the active fraction against the dermatophytes were identified by gas chromatography-mass spectrometry and high-performance liquid chromatography analysis. The antifungal activities of S. aromaticum oil (clove oil) against the dermatophytes tested were highest at a concentration of 0.2 mg/ml, with an effectiveness of more than 60%. Hyphal growth was completely inhibited in T. mentagrophytes, T. rubrum, and M. gypseum by treatment with clove oil at a concentration of 0.2 mg/ml. Eugenol was the most effective antifungal constituent of clove oil against the dermatophytes T. mentagrophytes and M. canis. Morphological changes in the hyphae of T. mentagrophytes, such as damage to the cell wall and cell membrane and the expansion of the endoplasmic reticulum, after treatment with 0.11 mg/ml eugenol were observed by transmission electron microscopy (TEM). At a concentration of 0.2 mg/ml, L. petersonii oil (LPO) was more than 90% effective against all of the dermatophytes tested, with the exception of T. rubrum. Geranial was determined to be the most active antifungal constituent of L. petersonii oil. Taken together, the results of this study demonstrate that clove and tea tree oils exhibited significant antifungal activities against the dermatophytes tested in this study.

Candida Species Biofilms’ Antifungal Resistance

PubMed Central

Silva, Sónia; Rodrigues, Célia F.; Araújo, Daniela; Rodrigues, Maria Elisa; Henriques, Mariana

2017-01-01

Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. PMID:29371527

Cuticular antifungals in spiders: density- and condition dependence.

PubMed

González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

2014-01-01

Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders.

Cuticular Antifungals in Spiders: Density- and Condition Dependence

PubMed Central

González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

2014-01-01

Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders. PMID:24637563

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives▿

PubMed Central

Burger-Kentischer, Anke; Finkelmeier, Doris; Keller, Petra; Bauer, Jörg; Eickhoff, Holger; Kleymann, Gerald; Abu Rayyan, Walid; Singh, Anurag; Schröppel, Klaus; Lemuth, Karin; Wiesmüller, Karl-Heinz; Rupp, Steffen

2011-01-01

Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic Candida yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules. PMID:21746957

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

PubMed Central

Scorzoni, Liliana; de Paula e Silva, Ana C. A.; Marcos, Caroline M.; Assato, Patrícia A.; de Melo, Wanessa C. M. A.; de Oliveira, Haroldo C.; Costa-Orlandi, Caroline B.; Mendes-Giannini, Maria J. S.; Fusco-Almeida, Ana M.

2017-01-01

The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of efflux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients. PMID:28167935

Antifungal mechanism of a novel antifungal protein from pumpkin rinds against various fungal pathogens.

PubMed

Park, Seong-Cheol; Kim, Jin-Young; Lee, Jong-Kook; Hwang, Indeok; Cheong, Hyeonsook; Nah, Jae-Woon; Hahm, Kyung-Soo; Park, Yoonkyung

2009-10-14

A novel antifungal protein (Pr-2) was identified from pumpkin rinds using water-soluble extraction, ultrafiltration, cation exchange chromatography, and reverse-phase high-performance liquid chromatography. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry indicated that the protein had a molecular mass of 14865.57 Da. Automated Edman degradation showed that the N-terminal sequence of Pr-2 was QGIGVGDNDGKRGKR-. The Pr-2 protein strongly inhibited in vitro growth of Botrytis cinerea, Colletotrichum coccodes, Fusarium solani, Fusarium oxysporum, and Trichoderma harzianum at 10-20 microM. The results of confocal laser scanning microscopy and SYTOX Green uptake demonstrated that its effective region was the membrane of the fungal cell surface. In addition, this protein was found to be noncytotoxic and heat-stable. Taken together, the results of this study indicate that Pr-2 is a good candidate for use as a natural antifungal agent.

Synthesis of natural acylphloroglucinol-based antifungal compounds against Cryptococcus species

USDA-ARS?s Scientific Manuscript database

Thirty-five analogs of naturally occurring acylphloroglucinols were designed and synthesized to identify antifungal compounds against Cryptococcus spp. that causes the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans...

Synergy of the antibiotic colistin with echinocandin antifungals in Candida species.

PubMed

Zeidler, Ute; Bougnoux, Marie-Elisabeth; Lupan, Alexandru; Helynck, Olivier; Doyen, Antonia; Garcia, Zacarias; Sertour, Natacha; Clavaud, Cécile; Munier-Lehmann, Hélène; Saveanu, Cosmin; d'Enfert, Christophe

2013-06-01

Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins.

The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

PubMed

Kim, Jin Seok; Cheong, June-Won; Kim, Yeo-Kyeoung; Park, Jinny; Mun, Yeung-Chul; Kang, Hye Jin; Yi, Hyeon Gyu; Lee, Je-Hwan; Kim, Yang Soo; Ryoo, Hun-Mo; Kim, Sung-Hyun; Kim, Ho Young; Kim, Jin Young; Lee, Dong-Gun; Kim, Hoon-Gu; Kim, Hawk; Joo, Young-Don; Min, Yoo Hong

2014-01-01

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

Genotyping and In Vitro Antifungal Susceptibility Testing of Fusarium Isolates from Onychomycosis in India.

PubMed

Gupta, Chhavi; Jongman, Marit; Das, Shukla; Snehaa, K; Bhattacharya, S N; Seyedmousavi, S; van Diepeningen, Anne D

2016-08-01

Onychomycosis refers to fungal infection of the nail and is commonly caused by dermatophytes, while yeasts and non-dermatophytic molds (NDM) are increasingly recognized as pathogens in nail infections. The present study was done to delineate molecular epidemiology of Fusarium onychomycosis in India. Five hundred nail samples of Indian patients clinically suspected of onychomycosis were subjected to direct microscopy and fungal culture. Representative Fusarium isolates were further identified to species level by multi-locus sequencing for internal transcribed spacer, translation elongation factor 1 alpha (tef1-α) and RNA polymerase II subunit (rpb2) regions (primer pairs: ITS1/ITS4, EF1/EF2, 5f2/7cr, respectively). These representative strains were also tested for in vitro antifungal susceptibility by the broth microdilution method. Members of the genus Fusarium proved to be the most common NDM responsible for onychomycosis. The Fusarium spp. responsible for onychomycosis belonged to the Fusarium solani species complex (F. keratoplasticum and F. falciforme) and Fusarium fujikuroi species complex (F. proliferatum, F. acutatum and F. sacchari). Antifungal susceptibility results indicated that amphotericin B was the most effective antifungal across all isolates (MIC ranging 0.5-2 mg/L), followed by voriconazole (MIC ranging 1-8 µg/ml). However, a large variation was shown in susceptibility to posaconazole (MIC ranging 0.5 to >16 µg/ml). To conclude, we identified different Fusarium spp. responsible for onychomycosis in India with variation within species in susceptibility to antifungal agents, showing that fusariosis requires correct and prompt diagnosis as well as antifungal susceptibility testing.

Bioactivity-Guided Metabolite Profiling of Feijoa ( Acca sellowiana) Cultivars Identifies 4-Cyclopentene-1,3-dione as a Potent Antifungal Inhibitor of Chitin Synthesis.

PubMed

Mokhtari, Mona; Jackson, Michael D; Brown, Alistair S; Ackerley, David F; Ritson, Nigel J; Keyzers, Robert A; Munkacsi, Andrew B

2018-06-06

Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa. Two novel cultivars were the most bioactive, and the compound 4-cyclopentene-1,3-dione, detected in these cultivars, was potently antifungal (IC 50 = 1-2 μM) against human-pathogenic Candida species. Haploinsufficiency and fluorescence microscopy analyses determined that the synthesis of chitin, a fungal-cell-wall polysaccharide, was the target of 4-cyclopentene-1,3-dione. This fungal-specific mechanism was consistent with a 22-70-fold reduction in antibacterial activity. Overall, we identified the agricultural waste product of specific cultivars of feijoa peels as a source of potential high-value antifungal compounds.

Isolation, identification and usefulness of antifungal compounds from Zuccagnia punctata for control of toxigenic ear rot pathogens.

PubMed

Jimenez, Cristina M; Sampietro, Diego A; Sgariglia, Melina A; Soberón, José R; Vattuone, Marta A

2014-10-01

Infusion, tincture and decoction of leaves of Zuccagnia punctata Cav. were assayed on growth of Fusarium verticillioides, F. graminearum sensu stricto, F. boothii, F. meridionale, F. subglutinans and F. thapsinum. The tincture showed the lowest IC50 on mycelial growth. A diethyl ether fraction of the tincture showed the highest antifungal activity in microdilution assays on F. verticillioides and F. graminearum. The antifungal constituents were separated by silica gel chromatography and identified as 2',4'-dihydroxychalcone, 2',4'-dihydroxy-3'-methoxychalcone and 7-hydroxy-3',4'-dimethoxyflavone. These chalcones had the lowest MIC and MFC values on F. verticillioides and F. graminearum sensu stricto. 2',4'-Dihydroxychalcone was mildly toxic and the remaining identified compounds were non-toxic in the brine shrimp assay. 2',4'-Dihydroxychalcone in mixtures with commercial food preservatives showed additive effects on F. graminearum sensu stricto and synergistic ones on F. verticillioides. 2',4'-Dihydroxy-3'-methoxychalcone showed synergistic effects in mixtures. Our results suggest that addition of chalcones to food preservatives allows reduction in the doses of the preservatives required for control of Fusarium species.

Antifungal activity, main active components and mechanism of Curcuma longa extract against Fusarium graminearum

PubMed Central

Zhang, Fusheng; Chen, Qin; Chen, Cheng; Yu, Xiaorui; Liu, Qingya; Bao, Jinku

2018-01-01

Curcuma longa possesses powerful antifungal activity, as demonstrated in many studies. In this study, the antifungal spectrum of Curcuma longa alcohol extract was determined, and the resulting EC50 values (mg/mL) of its extract on eleven fungi, including Fusarium graminearum, Fusarium chlamydosporum, Alternaria alternate, Fusarium tricinctum, Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium culmorum, Rhizopus oryzae, Cladosporium cladosporioides, Fusarium oxysporum and Colletotrichum higginsianum, were 0.1088, 0.1742, 0.1888, 0.2547, 0.3135, 0.3825, 0.4229, 1.2086, 4.5176, 3.8833 and 5.0183, respectively. Among them, F. graminearum was selected to determine the inhibitory effects of the compounds (including curdione, isocurcumenol, curcumenol, curzerene, β-elemene, curcumin, germacrone and curcumol) derived from Curcuma longa. In addition, the antifungal activities of curdione, curcumenol, curzerene, curcumol and isocurcumenol and the synergies of the complexes of curdione and seven other chemicals were investigated. Differential proteomics of F. graminearum was also compared, and at least 2021 reproducible protein spots were identified. Among these spots, 46 were classified as differentially expressed proteins, and these proteins are involved in energy metabolism, tRNA synthesis and glucose metabolism. Furthermore, several fungal physiological differences were also analysed. The antifungal effect included fungal cell membrane disruption and inhibition of ergosterol synthesis, respiration, succinate dehydrogenase (SDH) and NADH oxidase. PMID:29543859

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2012-06-13

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 09 February 2012. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Two trials were identified by the searches; neither was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Selective BET bromodomain inhibition as an antifungal therapeutic strategy

PubMed Central

Mietton, Flore; Ferri, Elena; Champleboux, Morgane; Zala, Ninon; Maubon, Danièle; Zhou, Yingsheng; Harbut, Mike; Spittler, Didier; Garnaud, Cécile; Courçon, Marie; Chauvel, Murielle; d'Enfert, Christophe; Kashemirov, Boris A.; Hull, Mitchell; Cornet, Muriel; McKenna, Charles E.; Govin, Jérôme; Petosa, Carlo

2017-01-01

Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function. PMID:28516956

In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

PubMed

Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

2013-09-01

The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen. © 2013 Blackwell Verlag GmbH.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2014-11-28

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 17 March 2014. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2016-11-08

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 29 September 2016. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Oropharyngeal candidiasis in head and neck cancer patients in Iran: Species identification, antifungal susceptibility and pathogenic characterization.

PubMed

Jahanshiri, Z; Manifar, S; Moosa, H; Asghari-Paskiabi, F; Mahmoodzadeh, H; Shams-Ghahfarokhi, M; Razzaghi-Abyaneh, M

2018-06-01

Oropharyngeal candidiasis (OPC) is the most frequent opportunistic fungal infection in head and neck cancer patients. This study was done to identify the Candida species, which cause OPC, and to evaluate their antifungal susceptibility pattern and pathogenic characteristics in Iranian head and neck cancer patients treated by radiotherapy. The oral clinical samples were determined by culturing on CHROMagar, carbohydrate assimilation and ITS sequencing methods. Biofilm formation, phospholipase and proteinase activity and antifungal susceptibility were examined too. Among 54 patients with confirmed OPC, 39 (72.22%) patients were male and 15 (27.77%) were female. The most frequently Candida species from a total of 60 isolates was C. albicans (53.3%), followed by C. tropicalis (21.66%), C. glabrata (15%), C. kefyr (5%) and C. dubliniensis (1.66%). All the isolates were high-producers of biofilm. All of Candida isolates were proteinase positive and 47 isolates (81.04%) represented phospholipase activity. The maximum and minimum rates of antifungal resistance belonged to ketoconazole (93.75% of C. albicans and 89.28% of Candida non-albicans) and fluconazole (62.50% and 42.85% of C. albicans and Candida non-albicans), respectively. The most effective antifungal against all candida isolates was fluconazole. Our data can estimate abundance of OPC in male and female head and neck cancer patients and is helpful to use effective strategies for antifungal treatment, prophylaxis, and preventive therapies in these patients. Copyright © 2018. Published by Elsevier Masson SAS.

Microscopic Evaluation, Molecular Identification, Antifungal Susceptibility, and Clinical Outcomes in Fusarium, Aspergillus and, Dematiaceous Keratitis

PubMed Central

Gajjar, Devarshi U.; Pal, Anuradha K.; Ghodadra, Bharat K.; Vasavada, Abhay R.

2013-01-01

Purpose. Fusarium, Aspergillus, and Dematiaceous are the most common fungal species causing keratitis in tropical countries. Herein we report a prospective study on fungal keratitis caused by these three fungal species. Methodology. A prospective investigation was undertaken to evaluate eyes with presumed fungal keratitis. All the fungal isolates (n = 73) obtained from keratitis infections were identified using morphological and microscopic characters. Molecular identification using sequencing of the ITS region and antifungal susceptibility tests using microdilution method were done. The final clinical outcome was evaluated in terms of the time taken for resolution of keratitis and the final visual outcome. The results were analyzed after segregating the cases into three groups, namely, Fusarium, Aspergillus, and Dematiaceous keratitis. Results. Diagnosis of fungal keratitis was established in 73 (35.9%) cases out of 208 cases. The spectra of fungi isolated were Fusarium spp. (26.6%), Aspergillus spp. (21.6%), and Dematiaceous fungi (11.6%). The sequence of the ITS region could identify the Fusarium and Aspergillus species at the species complex level, and the Dematiaceous isolates were accurately identified. Using antifungal agents such as fluconazole, natamycin, amphotericin B, and itraconazole, the minimum inhibitory concentrations (MICs) for Fusarium spp. were >32 μg/mL, 4–8 μg/mL, 0.5–1 μg/mL, and >32 μg/mL, respectively. Antifungal susceptibility data showed that Curvularia spp. was highly resistant to all the antifungal agents. Overall, natamycin and amphotericin B were found to be the most effective antifungal agents. The comparative clinical outcomes in all cases showed that the healing response in terms of visual acuity of the Dematiaceous group was significantly good when compared with the Fusarium and Aspergillus groups (P < 0.05). The time required for healing in the Fusarium group was statistically significantly less when compared with the Aspergillus and Dematiaceous groups. Conclusion. This study demonstrates important differences in microscopic features of scraping material and antifungal susceptibility between the three groups. Early and accurate identification coupled with the MIC data, and thereby appropriate treatment is crucial for complete recovery. PMID:24260740

Antimicrobial agents from Licaria puchuri-major and their synergistic effect with polygodial.

PubMed

Himejima, M; Kubo, I

1992-05-01

The resistance of the seeds of Licaria puchuri-major (Lauraceae) to decomposition in nature seems to be due largely to chemical defense, since its n-hexane extract contains antimicrobial principles in quantity, with a broad antimicrobial spectrum. In order to identify the active principles, the n-hexane extract was steam-distilled to yield a distillate and a residue. Subsequent bioassay indicated that the distillate retained the original broad antimicrobial activity, while the residue exhibited almost no activity. Gc-ms analysis showed that the distillate contained four phenolic compounds, seven monoterpenes, and one sesquiterpene. In contrast, the residue contained, almost exclusively, lauric acid. In the detailed antimicrobial assay with the pure compounds identified, most of them showed broad, but moderate, antimicrobial activity. Some of the components identified in the distillate were combined with polygodial [1] in order to enhance their antifungal activity. Unexpectedly, while polygodial did not synergize the antifungal activity of any of the compounds tested, the antifungal activity of polygodial was significantly increased when combined with aromatic substances such as anethole, safrole, or methyleugenol.

Synergistic Activity between Two Antifungal Proteins, the Plant Defensin NaD1 and the Bovine Pancreatic Trypsin Inhibitor

PubMed Central

Dawson, Charlotte S.; McKenna, James A.; Quimbar, Pedro; Hayes, Brigitte M. E.; van der Weerden, Nicole L.

2017-01-01

ABSTRACT Defensins are a large family of small, cationic, cysteine-rich proteins that are part of the defense arsenal that plants use for protection against potentially damaging fungal infections. The plant defensin NaD1 from Nicotiana alata is a potent antifungal protein that inhibits growth and kills a variety of fungal pathogens that affect both plant and animal (human) hosts. Some serine protease inhibitors have also been reported to be antifungal molecules, while others have no inhibitory activity against fungi. Here we describe the synergistic activity of the plant defensin NaD1 with a selection of serine protease inhibitors against the plant pathogens Fusarium graminearum and Colletotrichum graminicola and the animal pathogen Candida albicans. The synergistic activity was not related to the protease inhibitory activity of these molecules but may arise from activation of fungal stress response pathways. The bovine pancreatic trypsin inhibitor (BPTI) displayed the most synergy with NaD1. BPTI also acted synergistically with several other antifungal molecules. The observation that NaD1 acts synergistically with protease inhibitors provides the foundation for the design of transgenic plants with improved resistance to fungal disease. It also supports the possibility of naturally occurring accessory factors that function to enhance the activity of innate immunity peptides in biological systems. IMPORTANCE This work describes the increased activity of a natural antifungal peptide in the presence of another antifungal peptide from a different family. This is termed antifungal synergy. Synergy is important for decreasing the amount of antifungal molecule needed to control the disease. Traditionally, naturally occurring antifungal molecules are assayed in isolation. Identification of synergistic interactions between antifungal peptides means that their activities in a complex biological system are likely to be different from what we observe when examining them individually. This study identified synergy between an antifungal peptide and a group of peptides that do not affect fungal growth in vitro. This provides the foundation for generation of transgenic plants with increased resistance to fungal disease and identification of antifungal accessory factors that enhance the activity of innate immune molecules but do not have an antifungal effect on their own. PMID:29062897

Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains of Candida glabrata

PubMed Central

de Oliveira, Jean Carlos Almeida

2017-01-01

Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), or micafungin (15.4%). Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC) and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections. PMID:28814823

Use of the Aspergillus oryzae actin gene promoter in a novel reporter system for exploring antifungal compounds and their target genes.

PubMed

Marui, Junichiro; Yoshimi, Akira; Hagiwara, Daisuke; Fujii-Watanabe, Yoshimi; Oda, Ken; Koike, Hideaki; Tamano, Koichi; Ishii, Tomoko; Sano, Motoaki; Machida, Masayuki; Abe, Keietsu

2010-08-01

Demand for novel antifungal drugs for medical and agricultural uses has been increasing because of the diversity of pathogenic fungi and the emergence of drug-resistant strains. Genomic resources for various living species, including pathogenic fungi, can be utilized to develop novel and effective antifungal compounds. We used Aspergillus oryzae as a model to construct a reporter system for exploring novel antifungal compounds and their target genes. The comprehensive gene expression analysis showed that the actin-encoding actB gene was transcriptionally highly induced by benomyl treatment. We therefore used the actB gene to construct a novel reporter system for monitoring responses to cytoskeletal stress in A. oryzae by introducing the actB promoter::EGFP fusion gene. Distinct fluorescence was observed in the reporter strain with minimum background noise in response to not only benomyl but also compounds inhibiting lipid metabolism that is closely related to cell membrane integrity. The fluorescent responses indicated that the reporter strain can be used to screen for lead compounds affecting fungal microtubule and cell membrane integrity, both of which are attractive antifungal targets. Furthermore, the reporter strain was shown to be technically applicable for identifying novel target genes of antifungal drugs triggering perturbation of fungal microtubules or membrane integrity.

Candida antifungal drug resistance in sub-Saharan African populations: A systematic review

PubMed Central

Africa, Charlene Wilma Joyce; Abrantes, Pedro Miguel dos Santos

2017-01-01

Background: Candida infections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection.  Objectives: This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa.  Methods: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinical Candida isolates from sub-Saharan African countries using Pubmed and Google Scholar.  Results: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences in Candida species prevalence and resistance patterns were identified.  Discussion: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected by Candida drug resistance.  Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the high Candida drug resistance levels seen to be emerging in sub-Saharan Africa. PMID:28154753

Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform

PubMed Central

Dai, Tianhong; Fuchs, Beth B.; Coleman, Jeffrey J.; Prates, Renato A.; Astrakas, Christos; St. Denis, Tyler G.; Ribeiro, Martha S.; Mylonakis, Eleftherios; Hamblin, Michael R.; Tegos, George P.

2012-01-01

Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. PMID:22514547

Essential oil composition, antioxidant and antifungal activities of Salvia sclarea L. from Munzur Valley in Tunceli, Turkey.

PubMed

Yuce, E; Yildirim, N; Yildirim, N C; Paksoy, M Y; Bagci, E

2014-06-15

The essential oil composition and in vitro antioxidant and antifungal activity of the Salvia sclarea L. from Munzur Valley in Tunceli, Turkey were evaluated in this research. The in vitro antifungal activity of ethanol, hexane and aqueous extracts of S. sclarea against pathogen fungi Epicoccum nigrum and Colletotrichum coccodes were investigated. The essential oil of aerial parts of S. sclarea was obtained by hydrodistillation and was analysed by GC and GC—MS. Total antioxidant status was determined by using Rel assay diagnostics TAS assay kit (Lot.RL024) by Multiscan FC (Thermo). 33 compounds were identified representing the 85.0% of the total oil. The most abundant components (>5%) of the S. sclarea essential oils were caryophyllene oxide (24.1%), sclareol (11.5%), spathulenol (11.4%), 1H-naphtho (2,1,6) pyran (8.6%) and b—caryophyllene (5.1%). The best antifungal and antioxidant effect was seen in ethanolic S. sclarea extract. It can be said that Salvia sclerae could be used as natural antioxidant.

Cyclic dipeptides from lactic acid bacteria inhibit the proliferation of pathogenic fungi.

PubMed

Kwak, Min-Kyu; Liu, Rui; Kim, Min-Kyu; Moon, Dohyun; Kim, Andrew Hyoungjin; Song, Sung-Hyun; Kang, Sa-Ouk

2014-01-01

Lactobacillus plantarum LBP-K10 was identified to be the most potent antifungal strain from Korean traditional fermented vegetables. The culture filtrate of this strain showed remarkable antifungal activity against Ganoderma boninense. Five fractions from the culture filtrate were observed to have an inhibitory effect against G. boninense. Also, the electron ionization and chemical ionization indicated that these compounds might be cyclic dipeptides. Of the five active fractions, two fractions showed the most significant anti-Ganoderma activity, and one of these fractions inhibited the growth of Candida albicans. These compounds were identified to be cis-cyclo(L-Val-L-Pro) and cis-cyclo(L-Phe-L-Pro), as confirmed by X-ray crystallography.

Antifungal activity and cytotoxicity of extracts and triterpenoid saponins obtained from the aerial parts of Anagallis arvensis L.

PubMed

Soberón, José R; Sgariglia, Melina A; Pastoriza, Ana C; Soruco, Estela M; Jäger, Sebastián N; Labadie, Guillermo R; Sampietro, Diego A; Vattuone, Marta A

2017-05-05

Anagallis arvensis L. (Primulaceae) is used in argentinean northwestern traditional medicine to treat fungal infections. We are reporting the isolation and identification of compounds with antifungal activity against human pathogenic yeast Candida albicans, and toxicity evaluation. to study the antifungal activity of extracts and purified compounds obtained form A. arvensis aerial parts, alone and in combinations with fluconazole (FLU), and to study the toxicity of the active compounds. Disk diffusion assays were used to perform an activity-guided isolation of antifungal compounds from the aerial parts of A. arvensis. Broth dilution checkerboard and viable cell count assays were employed to determine the effects of samples and combinations of FLU + samples against Candida albicans. The chemical structures of active compounds were elucidated by spectroscopic analysis. Genotoxic and haemolytic effects of the isolated compounds were determined. Four triterpenoid saponins (1-4) were identified. Anagallisin C (AnC), exerted the highest inhibitory activity among the assayed compounds against C. albicans reference strain (ATCC 10231), with MIC-0 =1µg/mL. The Fractional Inhibitory Concentration Index (FICI=0.129) indicated a synergistic effect between AnC (0.125µg/mL) and FLU (0.031µg/mL) against C. albicans ATCC 10231. AnC inhibited C. albicans 12-99 FLU resistant strain (MIC-0 =1µg/mL), and the FICI=0.188 indicated a synergistic effect between AnC (0.125µg/mL) and fluconazole (16µg/mL). The combination AnC+ FLU exerted fungicidal activity against both C. albicans strains. AnC exerted inhibitory activity against C. albicans ATCC 10231 sessile cells (MIC 5 0=0.5µg/mL and MIC 80 =1µg/mL) and against C. albicans 12-99 sessile cells (MIC 5 0=0.75µg/mL and MIC 80 =1.25µg/mL). AnC exerted haemolytic effect against human red blood cells at 15µg/mL and did not exerted genotoxic effect on Bacillus subtilis rec strains. The antifungal activity and lack of genotoxic effects of AnC give support to the traditional use of A. arvensis as antifungal and makes AnC a compound of interest to expand the available antifungal drugs. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

In vitro susceptibility and multilocus sequence typing of Fusarium isolates causing keratitis.

PubMed

Dallé da Rosa, P; Nunes, A; Borges, R; Batista, B; Meneghello Fuentefria, A; Goldani, L Z

2018-05-17

Fungal keratitis is recognized as a significant cause of ocular morbidity and blindness especially in developing countries. In this study, we aimed to present the molecular identification and susceptibility of Fusarium isolates causing fungal keratitis in a university hospital in southern Brazil. The samples were identified using the second largest subunit of the RNA polymerase gene (RPB2) and the translation elongation factor 1-alpha (TEF1), while the antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. The majority of the isolates belonged to the Fusarium solani species complex (F. solani, F. keratoplasticum and F. falciforme) and Fusarium oxysporum species complex. Antifungal susceptibility has shown that amphotericin B and natamycin were the most effective antifungals across all isolates, followed by voriconazole. Variation among Fusarium complexes in their antifungal sensitivities was observed in our study. The identification of Fusarium species from human samples is important not only from an epidemiological viewpoint, but also for choosing the appropriate antifungal agent for difficult-to-treat Fusarium infections such as keratitis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Synthesis of chitosan derivative with diethyldithiocarbamate and its antifungal activity.

PubMed

Qin, Yukun; Xing, Ronge; Liu, Song; Li, Kecheng; Hu, Linfeng; Yu, Huahua; Chen, Xiaolin; Li, Pengcheng

2014-04-01

With an aim to discover novel chitosan derivatives with enhanced antifungal properties compared with chitosan. Diethyl dithiocarbamate chitosan (EtDTCCS) was investigated and its structure was well identified. The antifungal activity of EtDTCCS against Alternaria porri (A. porri), Gloeosporium theae sinensis Miyake (G. theae sinensis), and Stemphylium solani Weber (S. solani) was tested at 0.25, 0.5, and 1.0 mg/mL, respectively. Compared with plain chitosan, EtDTCCS shows better inhibitory effect with 93.2% inhibitory index on G. theae sinensis at 1.0 mg/mL, even stronger than for polyoxin (82.5%). It was inferred derivatives of this kind may find potential applications for the treatment of various crop-threatening diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical Composition and in Vitro Antifungal Activity Screening of the Allium ursinum L. (Liliaceae)

PubMed Central

Bagiu, Radu Vasile; Vlaicu, Brigitha; Butnariu, Monica

2012-01-01

The objective of the study was to summarize the methods for isolating and identifying natural sulfur compounds from Allium ursinum (ramson) and to discuss the active constituents with regard to antifungal action. Using chromatographic techniques, the active constituents were isolated and subsequently identified. Analyses by high-performance liquid chromatography (HPLC) suggested that these compounds were sulfur constituents, with a characteristic absorbance at 250 nm. Gas chromatography-mass spectrometry (GC-MS) analyses allowed the chemical structures of the isolated constituents to be postulated. We adopted the same methods to identify the health-giving profiling of ramsons and the effects are thought to be primarily derived from the presence and breakdown of the alk(en)ylcysteine sulphoxide, alliin and its subsequent breakdown to allicin (sulfur-compounds of ramson) in connection with antifungal action. The aim of the study was the characterization of the chemical composition of ramsons and the testing of the action of the in vitro extracts, on different strains of Candida albicans. The main goal was to highlight the most efficient extracts of Allium ursinum that can provide long-term antifungal activity without remissions. The extracts from Allium ursinum plants, inhibited growth of Candida spp. cells at concentrations ranging from 0.5 to 4.0 mg/mL, while that of adherent cells at concentrations ranging from 1.0 to > 4.0 mg/mL, depending on the yeast and plant species. PMID:22408399

Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.

PubMed

Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

2014-08-01

Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antifungal Prevention of Systemic Candidiasis in Immunocompetent ICU Adults: Systematic Review and Meta-Analysis of Clinical Trials.

PubMed

Dupont, Hervé; Mahjoub, Yazine; Chouaki, Taieb; Lorne, Emmanuel; Zogheib, Elie

2017-11-01

The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection. A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed. Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials.gov, as well as reference lists. The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs. Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74-1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35-0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19-1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection. Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.

Antioxidant and antifungal potential of methanol extracts of Phellinus spp. from Sonora, Mexico.

PubMed

Ayala-Zavala, Jesús Fernando; Silva-Espinoza, Brenda Adriana; Cruz-Valenzuela, Manuel Reynaldo; Villegas-Ochoa, Mónica Alejandra; Esqueda, Martín; González-Aguilar, Gustavo Adolfo; Calderón-López, Yazaric

2012-01-01

Among the potential natural sources of bioactive compounds, those of the macroscopic fungi Phellinus spp. have been identified by previous researches. Phenolic compounds are among the major antioxidant and antimicrobial contributors due to their bioactive properties. The goal of this study was to determine the total phenolic and flavonoid contents, and its relation with the antioxidant and antifungal activity of methanolic extracts of Phellinus gilvus, Phellinus rimosus and Phellinus badius, respectively. The collected and identified organisms of Phellinus spp. were treated with methanol and the generated aqueous extract was analyzed to quantified total phenolic compounds, total flavonoids, radical scavenging activity against DPPH, trolox equivalent antioxidant capacity, and oxygen absorbance capacity. The antifungal property of the extracts was evaluated against Alternaria alternata. The content of phenolic compounds was of 49.31, 46.51 and 44.7 mg of gallic acid equivalents/g, for P. gilvus, P. rimosus and P. badius, respectively. The total flavonoid content followed the same pattern with values of 30.58, 28, and 26.48 mg of quercetin equivalents/g for P. gilvus, P. rimosus and P. badius, respectively. The variation on the content of phenolic components was reflected on the antioxidant activity of every organism. The antioxidant activity ranked as follows: P. gilvus>P. rimosus>P. badius. The antifungal effect of the different extracts against A. alternata showed a significant effect, all of them, inhibiting the growth of this pathogen. P. gilvus showed the best potential to inactivate free radicals, being all the tested fungi effective to inhibit A. alternata growth. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent.

PubMed

Park, Joonsoo; Kwon, Osung; An, Hyun-Jin; Park, Kwan Kyu

2018-04-01

Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl ( p =0.026) and 40 mg/100 µl ( p =0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl ( p =0.000) and 300 µl/100 µl ( p =0.030). The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

PubMed

Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

2017-02-01

Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The Society for Applied Microbiology.

Expression profiling of Bombyx mori gloverin2 gene and its synergistic antifungal effect with cecropin A against Beauveria bassiana.

PubMed

Lü, Dingding; Geng, Tao; Hou, Chengxiang; Qin, Guangxing; Gao, Kun; Guo, Xijie

2017-02-05

Gloverin2 is a cationic and glycine-rich antimicrobial peptide whose expression can be induced in fat body of silkworm (Bombyx mori) larvae exposed to bacteria. The purpose of this study is to identify the roles of Bombyx mori gloverin2 (Bmgloverin2) during entomopathogenic fungus Beauveria bassiana infection. Fluorescent quantitative real-time PCR analysis indicated that the relative expression level of Bmgloverin2 gene was up-regulated in the silkworm larvae infected by B. bassiana. The cDNA of Bmgloverin2 was cloned from the silkworm by RT-PCR and the DNA segment of the Bmgloverin2 peptide (without signal peptide sequence) was inserted into pCzn1 expression plasmid and expressed in E. coli ArcticExpress (DE3). SDS-PAGE results revealed that soluble recombinant Bmgloverin2 was successfully expressed and purified. Polyclonal antibody against the Bmgloverin2 was successfully produced with the expressed recombinant protein. Western blot analysis indicated that Bmgloverin2 could be detected in the fat body of silkworm larvae infected with B. bassiana, suggesting that the expression of Bmgloverin2 could be induced by B. bassiana infection in silkworm. Antifungal assays indicated that the Bmgloverin2 had a synergistic antifungal activity with B. mori cecropin A (BmCecA) to entomopathogenic fungus B. bassiana both in vitro and in vivo in the silkworm larvae. This is the first report that Bmgloverin2 exhibits synergistic effect with BmCecA in antifungal activity against B. bassiana. The study demonstrates that Bmgloverin2 is an antifungal protein which plays an important role in synergistic antifungal activity with other antimicrobial peptide in silkworm. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of antifungal activity of standardized extract of Salvia rhytidea Benth. (Lamiaceae) against various Candida isolates.

PubMed

Salari, S; Bakhshi, T; Sharififar, F; Naseri, A; Ghasemi Nejad Almani, P

2016-12-01

Salvia species have long been described in traditional medicine for various indications. Owing to the widespread use of this genus by ethnic populations, especially for various infections ranging from skin disease to gastrointestinal disorders, we were encouraged to determine whether Salvia rhytidea could be effective against fungal infections. Given the increased incidence of candidiasis in the past decade, limits on the use of antifungal drugs, emergence of azole-resistant Candida species and increased incidence of treatment failures, it is necessary to identify a novel agent with antifungal properties. Aim of the study was to evaluate the antifungal properties of S. rhytidea against various Candida isolates. In this study, at first rosmarinic acid content of plant extract was determined. A total of 96 Candida isolates were tested, including the following species: Candida albicans (n=42), Candida glabrata (n=16), Candida tropicalis (n=11), Candida krusei (n=9), Candida parapsilosis (n=9), Candida lusitaniae (n=7) and Candida guilliermondii (n=2). The in vitro antifungal activity of methanolic extracts of S. rhytidea Benth. was evaluated against Candida isolates and compared with that of the standard antifungal drug nystatin by using a broth microdilution method, according to CLSI. Phytochemical screening results showed that the methanolic extract of S. rhytidea Benth. was rich in flavonoids and tannins. The minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of S. rhytidea Benth. ranged from 3.125 to>100μg/ml and 6.25 to>100μg/ml respectively. The growth inhibition value displayed that C. tropicalis, C. krusei and C. albicans isolates were most susceptible to S. rhytidea. Findings show that S. rhytidea possesses an antifungal effect against Candida isolates. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antibacterial and Antifungal Activity of Holothuria leucospilota Isolated From Persian Gulf and Oman Sea

PubMed Central

Adibpour, Neda; Nasr, Farhad; Nematpour, Fatemeh; Shakouri, Arash; Ameri, Abdolghani

2014-01-01

Background: Emergence of antimicrobial resistance toward a number of conventional antibiotics has triggered the search for antimicrobial agents from a variety of sources including the marine environment. Objectives: The aim of this study was to evaluate the antimicrobial potential of Holothuria leucospilota from Qeshm and Kharg Islands against some selected bacteria and fungi. Materials and Methods: In this investigation, sea cucumbers from two coastal cities of Persian Gulf were collected in March and May 2011 and identified by the scale method according to the food and agriculture organization of the United Nations. Antibacterial activity of hydroalcoholic extracts of the body wall, cuvierian organs and coelomic fluid, methanol, chloroform, and n-hexane extracts of the body wall were evaluated by the spot test. In addition, their antifungal activity was assessed by the broth dilution method. Results: The displayed effect was microbiostatic at concentrations of 1000 and 2000 µg/mL rather than microbicidal. The highest activity of hydroalcoholic extracts was exhibited by body wall, cuvierian organs and coelomic fluid against Escherichia coli, Salmonella typhi, Staphylococcus aureus and Pseudomonas aeruginosa; Aspergillus niger, A. fumigatus, A. flavus and A. brasilensis. However, none of the methanol, chloroform and n-haxane extracts showed appreciable effects against Shigella dysenteriae, Proteus vulgaris, Bacillus cereus, S. epidermidis and Candida albicans. Moreover, cuvierian organs did not possess any antifungal potential. Conclusions: Our data indicated that water-methanol extracts from the body wall of H. leucospilota possess antibacterial and antifungal activity. However, additional and in-depth studies are required to isolate and identify the active component(s). PMID:25147657

Common drug-drug interactions in antifungal treatments for superficial fungal infections.

PubMed

Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H

2018-04-01

Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.

Plant-derived antifungal agent poacic acid targets β-1,3-glucan

PubMed Central

Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; Li, Sheena C.; Hinchman, Li; Ranjan, Ashish; Smith, Damon L.; Higbee, Alan J.; Ulbrich, Arne; Coon, Joshua J.; Deshpande, Raamesh; Bukhman, Yury V.; McIlwain, Sean; Ong, Irene M.; Myers, Chad L.; Boone, Charles; Landick, Robert; Ralph, John; Kabbage, Mehdi; Ohya, Yoshikazu

2015-01-01

A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates. PMID:25775513

Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014

PubMed Central

Wang, HaiKuan; Yan, YanHua; Wang, JiaMing; Zhang, HePing; Qi, Wei

2012-01-01

Lactobacillus plantarum IMAU10014 was isolated from koumiss that produces a broad spectrum of antifungal compounds, all of which were active against plant pathogenic fungi in an agar plate assay. Two major antifungal compounds were extracted from the cell-free supernatant broth of L. plantarum IMAU10014. 3-phenyllactic acid and Benzeneacetic acid, 2-propenyl ester were carried out by HPLC, LC-MS, GC-MS, NMR analysis. It is the first report that lactic acid bacteria produce antifungal Benzeneacetic acid, 2-propenyl ester. Of these, the antifungal products also have a broad spectrum of antifungal activity, namely against Botrytis cinerea, Glomerella cingulate, Phytophthora drechsleri Tucker, Penicillium citrinum, Penicillium digitatum and Fusarium oxysporum, which was identified by the overlay and well-diffusion assay. F. oxysporum, P. citrinum and P. drechsleri Tucker were the most sensitive among molds. PMID:22276116

Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

PubMed

Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

2016-01-01

The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

PubMed Central

Zhang, Lixin; Yan, Kezhi; Zhang, Yu; Huang, Ren; Bian, Jiang; Zheng, Chuansen; Sun, Haixiang; Chen, Zhihui; Sun, Nuo; An, Rong; Min, Fangui; Zhao, Weibo; Zhuo, Ying; You, Jianlan; Song, Yongjie; Yu, Zhenyan; Liu, Zhiheng; Yang, Keqian; Gao, Hong; Dai, Huanqin; Zhang, Xiaoli; Wang, Jian; Fu, Chengzhang; Pei, Gang; Liu, Jintao; Zhang, Si; Goodfellow, Michael; Jiang, Yuanying; Kuai, Jun; Zhou, Guochun; Chen, Xiaoping

2007-01-01

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of ≈20,000 microbial extracts, 12 hits were identified with broad-spectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy. PMID:17360571

Endophytic fungus strain 28 isolated from Houttuynia cordata possesses wide-spectrum antifungal activity.

PubMed

Pan, Feng; Liu, Zheng-Qiong; Chen, Que; Xu, Ying-Wen; Hou, Kai; Wu, Wei

2016-01-01

The aim of this paper is to identify and investigate an endophytic fungus (strain 28) that was isolated from Houttuynia cordata Thunb, a famous and widely-used Traditional Chinese Medicine. Based on morphological methods and a phylogenetic analysis of ITS sequences, this strain was identified as Chaetomium globosum. An antifungal activity bioassay demonstrated that the crude ethyl acetate (EtOAc) extracts of strain 28 had a wide antifungal spectrum and strong antimicrobial activity, particularly against Exserohilum turcicum (Pass.) Leonard et Suggs, Botrytis cinerea persoon and Botrytis cinerea Pers. ex Fr. Furthermore, the fermentation conditions, extraction method and the heat stability of antifungal substances from strain 28 were also studied. The results showed that optimal antifungal activity can be obtained with the following parameters: using potato dextrose broth (PDB) as the base culture medium, fermentation for 4-8d (initial pH: 7.5), followed by extraction with EtOAc. The extract was stable at temperatures up to 80°C. This is the first report on the isolation of endophytic C. globosum from H. cordata to identify potential alternative biocontrol agents that could provide new opportunities for practical applications involving H. cordata. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Species Identification and In Vitro Antifungal Susceptibility of Aspergillus terreus Species Complex Clinical Isolates from a French Multicenter Study.

PubMed

Imbert, S; Normand, A C; Ranque, S; Costa, J M; Guitard, J; Accoceberry, I; Bonnal, C; Fekkar, A; Bourgeois, N; Houzé, S; Hennequin, C; Piarroux, R; Dannaoui, E; Botterel, F

2018-05-01

Aspergillus section Terrei is a species complex currently comprised of 14 cryptic species whose prevalence in clinical samples as well as antifungal susceptibility are poorly known. The aims of this study were to investigate A. Terrei clinical isolates at the species level and to perform antifungal susceptibility analyses by reference and commercial methods. Eighty-two clinical A. Terrei isolates were collected from 8 French university hospitals. Molecular identification was performed by sequencing parts of beta-tubulin and calmodulin genes. MICs or minimum effective concentrations (MECs) were determined for 8 antifungal drugs using both EUCAST broth microdilution (BMD) methods and concentration gradient strips (CGS). Among the 79 A. Terrei isolates, A. terreus stricto sensu ( n = 61), A. citrinoterreus ( n = 13), A. hortai ( n = 3), and A. alabamensis ( n = 2) were identified. All strains had MICs of ≥1 mg/liter for amphotericin B, except for two isolates (both A. hortai ) that had MICs of 0.25 mg/liter. Four A. terreus isolates were resistant to at least one azole drug, including one with pan-azole resistance, yet no mutation in the CYP51A gene was found. All strains had low MECs for the three echinocandins. The essential agreements (EAs) between BMD and CGS were >90%, except for those of amphotericin B (79.7%) and itraconazole (73.4%). Isolates belonging to the A section Terrei identified in clinical samples show wider species diversity beyond the known A. terreus sensu stricto Azole resistance inside the section Terrei is uncommon and is not related to CYP51A mutations here. Finally, CGS is an interesting alternative for routine antifungal susceptibility testing. Copyright © 2018 American Society for Microbiology.

Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

PubMed

Rao, Qi; Guo, Wenbin; Chen, Xinhua

2015-05-01

A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi.

Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum

PubMed Central

Singh, Vineeta; Praveen, Vandana; Tripathi, Divya; Haque, Shafiul; Somvanshi, Pallavi; Katti, S. B.; Tripathi, C. K. M.

2015-01-01

During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability. PMID:26159770

Antifungal activity of extracts from Atacama Desert fungi against Paracoccidioides brasiliensis and identification of Aspergillus felis as a promising source of natural bioactive compounds

PubMed Central

Mendes, Graziele; Gonçalves, Vívian N; Souza-Fagundes, Elaine M; Kohlhoff, Markus; Rosa, Carlos A; Zani, Carlos L; Cota, Betania B; Rosa, Luiz H; Johann, Susana

2016-01-01

Fungi of the genus Paracoccidioides are responsible for paracoccidioidomycosis. The occurrence of drug toxicity and relapse in this disease justify the development of new antifungal agents. Compounds extracted from fungal extract have showing antifungal activity. Extracts of 78 fungi isolated from rocks of the Atacama Desert were tested in a microdilution assay against Paracoccidioides brasiliensis Pb18. Approximately 18% (5) of the extracts showed minimum inhibitory concentration (MIC) values≤ 125.0 µg/mL. Among these, extract from the fungus UFMGCB 8030 demonstrated the best results, with an MIC of 15.6 µg/mL. This isolate was identified as Aspergillus felis (by macro and micromorphologies, and internal transcribed spacer, β-tubulin, and ribosomal polymerase II gene analyses) and was grown in five different culture media and extracted with various solvents to optimise its antifungal activity. Potato dextrose agar culture and dichloromethane extraction resulted in an MIC of 1.9 µg/mL against P. brasiliensis and did not show cytotoxicity at the concentrations tested in normal mammalian cell (Vero). This extract was subjected to bioassay-guided fractionation using analytical C18RP-high-performance liquid chromatography (HPLC) and an antifungal assay using P. brasiliensis. Analysis of the active fractions by HPLC-high resolution mass spectrometry allowed us to identify the antifungal agents present in the A. felis extracts cytochalasins. These results reveal the potential of A. felis as a producer of bioactive compounds with antifungal activity. PMID:27008375

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study.

PubMed

Harrison, D; Muskett, H; Harvey, S; Grieve, R; Shahin, J; Patel, K; Sadique, Z; Allen, E; Dybowski, R; Jit, M; Edgeworth, J; Kibbler, C; Barnes, R; Soni, N; Rowan, K

2013-02-01

There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. Ninety-six UK adult general critical care units. Consecutive admissions to participating critical care units. None. Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs. The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis. Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Isolation and characterization of antifungal compound from Lactobacillus plantarum KCC-10 from forage silage with potential beneficial properties.

PubMed

Valan Arasu, M; Jung, M-W; Ilavenil, S; Jane, M; Kim, D-H; Lee, K-D; Park, H-S; Hur, T-Y; Choi, G-J; Lim, Y-C; Al-Dhabi, N A; Choi, K-C

2013-11-01

The purpose of this study was to isolate, identify and characterize an antifungal compound from Lactobacillus plantarum KCC-10 from forage silage with potential beneficial properties. The 16S rRNA gene-based phylogenetic affiliation was determined using bioinformatic tools and identified as Lactobacillus sp. KCC-10 with 100% sequence similarity to L. plantarum. The antifungal substances were extracted with ethyl acetate from spent medium in which Lactobacillus sp. KCC-10 was cultivated. Antifungal activity was assessed using the broth microdilution technique. The compounds were obtained by eluting the crude extract with various concentrations of solvents followed by chromatographic purification. Based on the infrared, (13) C nuclear magnetic resonance (NMR) and (1) H NMR spectral data, the compound was identified as a phenolic-related antibiotic. The minimum inhibitory concentration of the compound against Aspergillus clavatus, A. oryzae, Botrytis elliptica and Scytalidium vaccinii was 2.5 mg ml(-1) and that against A. fumigatus, A. niger and S. fusca was 5.0 mg ml(-1) , respectively. In addition, Lactobacillus sp. KCC-10 was highly sensitive towards oxgall (0.3%) but grew well in the presence of sodium taurocholate (0.3%). An antimicrobial susceptibility pattern was an intrinsic feature of this strain; thus, consumption does not represent a health risk to humans or animals. Novel L. plantarum KCC-10 with antifungal and potential probiotic properties was characterized for use in animal food. This study revealed that L. plantarum KCC-10 exhibited good antifungal activity similar to that of probiotic Lactobacillus strains. © 2013 The Society for Applied Microbiology.

Chemosensitization as a Means to Augment Commercial Antifungal Agents

PubMed Central

Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

2012-01-01

Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance. PMID:22393330

Oropharyngeal candidiasis in HIV-infected patients under treatment with protease inhibitors.

PubMed

Migliorati, Cesar Augusto; Birman, Esther Goldenberg; Cury, Arlete Emily

2004-09-01

Oropharyngeal candidiasis decreased when protease inhibitors were included with other antiretrovirals to treat HIV infection. We tested oral yeast isolates of Brazilian HIV-infected individuals receiving antiretroviral therapy for protease secretion and susceptibility to ritonavir and some antifungals. We collected oral samples and identified yeasts from 19 HIV-infected patients receiving highly active antiretroviral therapy (HAART) and suspected of having oral candidiasis. Ritonavir and its excipients' effects on the isolated yeasts were tested for protease secretion by Rüchel's technique. The yeasts' susceptibility to amphotericin B (AnB), fluorocitosine (5FC), fluconazole (FZL), ketoconazole (KZL), and itraconazole (IZL) was determined by E-test (AB Biodisk). Chi-squared test determined the statistical differences. Twenty-five different positive isolates were obtained. Sixty-eight percent were C. albicans. Other isolates included C. famata (16%), C. glabrata (4%), C. tropicalis (4%), T. capitatum (4%), and 1 isolate not identified. High protease secretion was observed for most of the isolates (20/25). Ritonavir only altered enzyme secretion in 6/20 of the protease-secreting isolates. All isolates were highly sensitive to both AnB and 5FC. Antifungal activity did not change when ritonavir was added to the culture media. Some isolates were highly resistant to studied antifungals (52.2% KZL, 30.4% FZL, and 26% IZL). Resistance significantly decreased when ritonavir was added to the medium with KZL and IZL (P <.5 by chi-squared). A trend to decreased resistance was also observed with FZL but the results were not statistically significant. Candida continues to be the most prevalent fungus in the oral cavity. Although oral candidal isolates secrete protease, ritonavir does not inhibit all protease-secreting oral yeast isolates. There seems to be a synergistic effect between ritonavir and oral antifungals against fungal resistance.

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

PubMed Central

Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Espigado, Ildefonso; Ruiz Pérez de Pipaon, Maite; Falantes, José; de la Cruz, Fátima; Cisneros, José M.

2012-01-01

Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials. PMID:22058202

Plant-derived antifungal agent poacic acid targets β-1,3-glucan

DOE PAGES

Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; ...

2015-03-09

A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole.more » The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. In conclusion, the discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.« less

Evaluation of 1,3-benzoxathiol-2-one Derivatives as Potential Antifungal Agents.

PubMed

Terra, Luciana; de L Chazin, Eliza; de S Sanches, Paola; Saito, Max; de Souza, Marcus V N; Gomes, Claudia R B; Wardell, James L; Wardell, Solange M S V; Sathler, Plinio C; Silva, Gabriela C C; Lione, Viviane O; Kalil, Marcos; Joffily, Ana; Castro, Helena C; Vasconcelos, Thatyana R A

2018-01-01

Over the last few years, fungal infections have emerged as a worrisome global public health problem. Candidiasis is a disease caused by Candida species and has been a problem worldwide mainly for immunosuppressed patients. Lately, the resistant strains and side effects have been reported as important issues for treating Candidiasis, which have to be solved by identifying new drugs. The goal of this work was to synthesize a series of 1,3-benzoxathiol-2-one derivatives, XYbenzo[ d][1,3]oxathiol-2-ones, and evaluate their antifungal activity against five Candida species. In vitro antifungal screening test and minimum inhibitory concentration determination were performed according to CLSI protocols using ketoconazole as the reference drug. The cytotoxicity of the most active compounds was evaluated by hemolysis and MTT (Vero cells) assays. Compounds 2 (XY = 6-hydroxy-5-nitro, MIC = 4-32 µg/mL) and 7 (XY = 6-acetoxy-5-nitro, MIC =16-64 µg/mL) showed good results when compared with current antifungals in CLSI values (MIC = 0.04-250 µg/mL). These compounds exhibited a safer cytotoxicity as well as a lower hemolytic profile than ketoconazole. Overall, the in vitro results pointed to the potential of compounds 2 and 7 as new antifungal prototypes to be further explored. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

PubMed

Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

2016-01-01

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

Antifungal activity of fabrics knitted by metalized Silver/Polyester composite yarn

NASA Astrophysics Data System (ADS)

Özkan, İ.; Duru Baykal, P.

2017-10-01

In this study, antifungal properties of fabric knitted from metalized silver/polyester composite yarn were investigated. Intermingling is an alternative technique for yarn blending process. Yarns having different features can be combined by feeding the same intermingling jet. This process is defined as commingling. In the study, intermingling process was used to produce metalized silver/polyester composite yarn. Commingled yarns were knitted to single jersey fabrics by IPM brand sample type circular knitting machine. Antifungal activity test was applied to samples against Aspergillus Niger according to AATCC 30 test procedure. It has been identified that the application provides antifungal activity to fabric.

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

PubMed

Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

2016-02-12

With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

Effect of Addition of Antifungal Agents on Physical and Biological Properties of a Tissue Conditioner: An In-Vitro Study.

PubMed

Rawat, Pragati; Agarwal, Swatantra; Tripathi, Siddhi

2017-09-01

Purpose: Tissue conditioners are used for healing of abused oral tissues. They may harbour microorganisms causing oral diseases such as candidiasis compromising the health of the patient. Also, addition of antifungal agents into tissue conditioner may alter its properties. This study compares the anti-fungal property and mechanical properties of tissue conditioner containing different antifungal agents. Methods: Three antifungal agents, one synthetic - fluconazole, and two natural - oregano oil and virgin coconut oil were added into the tissue conditioner (Viscogel) in different concentrations. The antifungal property, tensile bond strength and viscoelasticity of Viscogel containing these antifungal agents were assessed after 24 hours, three days and seven days. Results: While, the highest antifungal activity was shown by Viscogel containing fluconazole, the maximum tensile bond strength was found to be of Viscogel alone (control). Although Viscogel alone and in combination of fluconazole showed deterioration in viscoelasticity, Viscogel in combination of natural agents showed no significant changes over the period of seven days. Conclusion: Incorporation of the natural agents in the tissue conditioner can be used as an effective alternative to systemic or topical synthetic antifungal agents.

Antifungal Drug Susceptibility of Candida Species Isolated from HIV-Positive Patients Recruited at a Public Hospital in São Luís, Maranhão, Brazil.

PubMed

Terças, Ana L G; Marques, Sirlei G; Moffa, Eduardo B; Alves, Márcia B; de Azevedo, Conceição M P S; Siqueira, Walter L; Monteiro, Cristina A

2017-01-01

Oropharyngeal candidiasis is the most common fungal infection in hospitalized patients with acquired immune deficiency syndrome (AIDS). Its progression results in invasive infections, which are a significant cause of morbidity and mortality. This study aimed to quickly and accurately identify Candida spp. from oral mucosa of AIDS patients recruited at Presidente Vargas Hospital, in São Luís city, Brazil and to evaluate the sensitivity profile of these fungi to antifungals by using an automated system. Isolates were collected from oropharyngeal mucosa of 52 hospitalized AIDS patients, under anti-viral and antifungal therapies. Patients were included in research if they were HIV-positive, above 18 years of age and after obtaining their written consent. CHROMagar ® Candida and the automated ViteK-2 ® system were used to isolate and identify Candida spp., respectively. Antifungal susceptibility testing was performed using the ViteK-2 ® system, complemented with the Etest ® , using the drugs amphotericin B, fluconazole, flucytosine, and voriconazole. Oropharyngeal candidiasis had a high prevalence in these hospitalized AIDS patients (83%), and the most prevalent species was Candida albicans (56%). Antifungal susceptibility test showed that 64.7% of the Candida spp. were susceptible, 11.8% were dose-dependent sensitive, and 23.5% were resistant. All the Candida krusei and Candida famata isolates and two of Candida glabrata were resistant to fluconazole. Most of AIDS patients presented oropharyngeal candidiasis and C. albicans was the most frequently isolated species. The results showed high variability in resistance among isolated species and indicates the need to identify the Candida spp. involved in the infection and the need to test antifungal susceptibility as a guide in drug therapy in patients hospitalized with AIDS. This is the first relate about AIDS patients monitoring in a public hospital in São Luís concerning the precise identification and establishing of antifungal profile of Candida spp..

Antifungal properties of essential oils for improvement of indoor air quality: a review.

PubMed

Whiley, Harriet; Gaskin, Sharyn; Schroder, Tiffany; Ross, Kirstin

2018-03-28

Concerns regarding indoor air quality, particularly the presence of fungi and moulds, are increasing. The potential for essential oils to reduce, control or remove fungi, is gaining interest as they are seen as a "natural" alternative to synthetic chemical fungicides. This review examines published research on essential oils as a method of fungal control in indoor environments. It was difficult to compare the relative performances of essential oils due to differences in research methods and reporting languages. In addition, there are limited studies that scale up laboratory results and assess the efficacy of essential oils within building environments. However, generally, there appears to be some evidence to support the essential oils clove oil, tea tree oil, oregano, thyme and lemon as potential antifungal agents. Essential oils from heartwood, marjoram, cinnamon, lemon basil, caraway, bay tree, fir, peppermint, pine, cedar leaf and manuka were identified in at least one study as having antifungal potential. Future studies should focus on comparing the effectiveness of these essential oils against a large number of fungal isolates from indoor environments. Studies will then need to focus on translating these results into realistic application methods, in actual buildings, and assess the potential for long-term antifungal persistence.

Anti-fungal activity of Morinda citrifolia (noni) extracts against Candida albicans: an in vitro study.

PubMed

Barani, K; Manipal, Sunayana; Prabu, D; Ahmed, Adil; Adusumilli, Preethi; Jeevika, C

2014-01-01

The aim of this study was to investigate the anti-fungal activity of Morinda citrifolia fruit extract on Candida albicans. Juice extract from M. citrifolia fruit was lyophilized and used in anti-fungal testing. Anti-fungal activity of M. citrifolia fruit extract against C. albicans was tested in vitro at various concentrations. The inhibitory effect of M. citrifolia extract on C. albicans was determined by agar culture and applied broth dilution test. M. citrifolia extract at 1000 μg/ml concentration effectively inhibited the growth of C. albicans (16.6 ± 0.3) compared with the positive control - amphotericin B (20.6 ± 0.6). It was found to be a dose-dependent reaction. M. citrifolia fruit extract had an anti-fungal effect on C. albicans and the inhibitory effect varied with concentration.

Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria

PubMed Central

Shishido, Tania K.; Jokela, Jouni; Kolehmainen, Clara-Theresia; Fewer, David P.; Wahlsten, Matti; Wang, Hao; Rouhiainen, Leo; Rizzi, Ermanno; De Bellis, Gianluca; Permi, Perttu; Sivonen, Kaarina

2015-01-01

Cyclodextrins are cyclic oligosaccharides widely used in the pharmaceutical industry to improve drug delivery and to increase the solubility of hydrophobic compounds. Anabaenolysins are lipopeptides produced by cyanobacteria with potent lytic activity in cholesterol-containing membranes. Here, we identified the 23- to 24-kb gene clusters responsible for the production of the lipopeptide anabaenolysin. The hybrid nonribosomal peptide synthetase and polyketide synthase biosynthetic gene cluster is encoded in the genomes of three anabaenolysin-producing strains of Anabaena. We detected previously unidentified strains producing known anabaenolysins A and B and discovered the production of new variants of anabaenolysins C and D. Bioassays demonstrated that anabaenolysins have weak antifungal activity against Candida albicans. Surprisingly, addition of the hydrophilic fraction of the whole-cell extracts increased the antifungal activity of the hydrophobic anabaenolysins. The fraction contained compounds identified by NMR as α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria. PMID:26474830

[Antifungal effects of three medicinal crops on Phytophthora nicotianae].

PubMed

He, Da-Min; Chen, Yang; Yang, Shui-Ping; Zhang, Xue; Zhao, Jian; Mo, Jing-Jing; Zhang, Dong-Yan; Zhao, Xin-Mei; Chen, Da-Xia; Ding, Wei

2017-09-01

Tobacco black shank is one of the most harmful soil-borne diseases infected by Phytophthora parasitica. In order to probe the control method to this disease, in this study, the mycelial growth rate method was employed to investigate the antifungal effects of extracts from stem-leaf and root, root exudates, and their combination of Scrophularia ningpoensis, Chuanmingshen violaceum and Pinellia ternata The results showed that: ①Stem-leaf and root extracts of S. ningpoensis, C. violaceum and P. ternata exhibited different antifungal activities, and the inhibition increased with the increase of extract concentration. The antifungal effect of S. ningpoensis extracts at 0.5 g•mL⁻¹ was the strongest than other medicinal plants, the inhibition rate of steam-leaf and root extracts reached 74.88%, 69.27%, respectively. The inhibitory effect of C. violaceum and P. ternata was relatively lower, however, there is a significant gain effect after combination of steam-leaf and root extracts of C. violaceum. ②The root exudates of S. ningpoensis, C. violaceum and P. ternata showed fungistasis to Phytophthora nicotianae, and fungistasis was enhanced with the increase of root exudate concentration. The antifungal effect in the order of C. violaceum > S. ningpoensis > P. ternata. ③The antifungal activity of combination of extract and root exudate from S. ningpoensis was similar with the effect of C. violaceum, they were both stronger than P. ternata, and the antifungal activity for three combination were located between the antifungal activity of their extracts and root exudates. S. ningpoensis and C. violaceum can be potentially applied to prevent and control the tobacco black shank. Copyright© by the Chinese Pharmaceutical Association.

Antifungal and antimycotoxigenic potency of Solanum torvum Swartz. leaf extract: isolation and identification of compound active against mycotoxigenic strains of Aspergillus flavus and Fusarium verticillioides.

PubMed

Abhishek, R U; Thippeswamy, S; Manjunath, K; Mohana, D C

2015-12-01

The main objective of this study was to investigate the antifungal effect of Solanum torvum leaves against different field and storage fungi, and to identify its active compound. In addition, to evaluate in vitro and in vivo inhibitory efficacy on toxigenic strains of Aspergillus flavus and Fusarium verticillioides. Leaves of S. torvum were sequentially extracted with petroleum ether, toluene, chloroform, methanol and ethanol. The antifungal compound isolated from chloroform extract was identified as torvoside K based on spectral analysis. The antifungal activity of chloroform extract and torvoside K was determined by broth microdilution and poisoned food techniques. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and zone of inhibition (ZOI) were recorded. Further, inhibitory effects of chloroform extract and torvoside K on growth of A. flavus and F. verticillioides, and their toxin productions were evaluated using in vitro and in vivo assays. Torvoside K showed the significant activity against tested fungi with ZOIs and MICs ranging from 33·4 to 87·4% and 31·25-250 μg ml(-1) , respectively. Further, torvoside K showed concentration-dependent antimycotoxigenic activity against aflatoxin B1 and fumonisin B1 production by A. flavus and F. verticillioides, respectively. It was observed that the compound torvoside K significantly inhibited the growth of all fungi tested. Growth of A. flavus and F. verticillioides, and aflatoxin B1 and fumonisin B1 productions were completely inhibited in vitro and in vivo by torvoside K with increasing concentration. Control of mycotoxigenic fungi requires compounds that able to inhibit both fungal growth and mycotoxin production. The antimycotoxigenic potential of torvoside K of S. torvum is described in this study for the first time. The results indicate the possible use of S. torvum as source of antifungal agents against postharvest fungal infestation of food commodities and mycotoxin contaminations. © 2015 The Society for Applied Microbiology.

Antifungal Indole and Pyrrolidine-2,4-Dione Derivative Peptidomimetic Lead Design Based on In Silico Study of Bioactive Peptide Families

PubMed Central

Moradi, Shoeib; Azerang, Parisa; Khalaj, Vahid; Sardari, Soroush

2013-01-01

Background The rise of opportunistic fungal infections highlights the need for development of new antimicrobial agents. Antimicrobial Peptides (AMPs) and Antifungal Peptides (AFPs) are among the agents with minimal resistance being developed against them, therefore they can be used as structural templates for design of new antimicrobial agents. Methods In the present study four antifungal peptidomimetic structures named C1 to C4 were designed based on plant defensin of Pisum sativum. Minimum inhibitory concentrations (MICs) for these structures were determined against Aspergillus niger N402, Candida albicans ATCC 10231, and Saccharomyces cerevisiae PTCC 5052. Results C1 and C2 showed more potent antifungal activity against these fungal strains compared to C3 and C4. The structure C2 demonstrated a potent antifungal activity among them and could be used as a template for future study on antifungal peptidomemetics design. Sequences alignments led to identifying antifungal decapeptide (KTCENLADTY) named KTC-Y, which its MIC was determined on fungal protoplast showing 25 (µg/ml) against Aspergillus fumigatus Af293. Conclusion The present approach to reach the antifungal molecules seems to be a powerful approach in design of bioactive agents based on AMP mimetic identification. PMID:23626876

A Mini HIP HOP Assay Uncovers a Central Role for Copper and Zinc in the Antifungal Mode of Action of Allicin.

PubMed

Prescott, Thomas A K; Panaretou, Barry

2017-05-10

Garlic contains the organosulfur compound allicin which exhibits potent antifungal activity. Here we demonstrate the use of a highly simplified yeast chemical genetic screen to characterize its mode of action. By screening 24 validated yeast gene deletion "signature" strains for which hypersensitivity is characteristic for common antifungal modes of action, yeast lacking the high affinity Cu 2+ transporter Ctr1 was found to be hypersensitive to allicin. Focusing on transition metal related genes identified two more hypersensitive strains lacking the Cu 2+ and Zn 2+ transcription factors Mac1 and Zap1. Hypersensitivity in these strains was reversed by the addition of Cu 2+ and Zn 2+ ions, respectively. The results suggest the antifungal activity of allicin is mediated through restricted Cu 2+ and Zn 2+ uptake or inhibition of Cu 2+ and Zn 2+ metalloproteins. As certain antimicrobial modes of action are much more common than others, the approach taken here provides a useful way to identify them early on.

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

PubMed Central

Hiller, Ekkehard; Istel, Fabian; Tscherner, Michael; Brunke, Sascha; Ames, Lauren; Firon, Arnaud; Green, Brian; Cabral, Vitor; Marcet-Houben, Marina; Jacobsen, Ilse D.; Quintin, Jessica; Seider, Katja; Frohner, Ingrid; Glaser, Walter; Jungwirth, Helmut; Bachellier-Bassi, Sophie; Chauvel, Murielle; Zeidler, Ute; Ferrandon, Dominique; Gabaldón, Toni; Hube, Bernhard; d'Enfert, Christophe; Rupp, Steffen; Cormack, Brendan; Haynes, Ken; Kuchler, Karl

2014-01-01

The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes. PMID:24945925

Overcoming antifungal resistance

PubMed Central

Srinivasan, Anand; Lopez-Ribot, Jose L.; Ramasubramanian, Anand K.

2014-01-01

Fungal infections have become one of the major causes of morbidity and mortality in immunocompromised patients. Despite increased awareness and improved treatment strategies, the frequent development of resistance to the antifungal drugs used in clinical settings contributes to the increasing toll of mycoses. Although a natural phenomenon, antifungal drug resistance can compromise advances in the development of effective diagnostic techniques and novel antifungals. In this review, we will discuss the advent of cellular-microarrays, microfluidics, genomics, proteomics and other state-of-the art technologies in conquering antifungal drug resistance. PMID:24847655

Occidiofungin is an important component responsible for the antifungal activity of Burkholderia pyrrocinia strain Lyc2.

PubMed

Wang, X Q; Liu, A X; Guerrero, A; Liu, J; Yu, X Q; Deng, P; Ma, L; Baird, S M; Smith, L; Li, X D; Lu, S E

2016-03-01

To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis. Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain. Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia. Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia. © 2015 The Society for Applied Microbiology.

Type III interferon is a critical regulator of innate antifungal immunity.

PubMed

Espinosa, Vanessa; Dutta, Orchi; McElrath, Constance; Du, Peicheng; Chang, Yun-Juan; Cicciarelli, Bryan; Pitler, Amy; Whitehead, Ian; Obar, Joshua J; Durbin, Joan E; Kotenko, Sergei V; Rivera, Amariliz

2017-10-06

Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus ( Af ) as a model to study antifungal immune responses, we found that depletion of CCR2 + monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2 + monocytes are an important early source of type I IFNs that prime optimal expression of IFN-λ. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2 + monocytes or by exogenous administration of IFN-α and IFN-λ. Thus, CCR2 + monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-λ expression. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The fungal resistome: a risk and an opportunity for the development of novel antifungal therapies.

PubMed

Reales-Calderón, Jose A; Molero, Gloria; Gil, Concha; Martínez, José L

2016-08-01

The risks for toxicity of novel antifungal compounds, together with the emergence of resistance, makes the use of inhibitors of resistance, in combination with antifungal compounds, a suitable strategy for developing novel antifungal formulations. Among them, inhibitors of efflux pumps are suitable candidates. Increasing drug influx or interfering with the stress response may also improve the efficacy of antifungals. Therapies as induction of fungal apoptosis or immunostimulation are also good strategies for reducing the risks for resistance and to improve antifungals' efficacy. Understanding the effect of the acquisition of resistance on the fungal physiology and determining the collateral sensitivity networks are useful for the development of novel strategies based on combination of antifungals for improving the efficacy of the therapy.

The antifungal action of dandruff shampoos.

PubMed

Bulmer, A C; Bulmer, G S

1999-01-01

The disease commonly known as "dandruff" is caused by numerous host factors in conjunction with the normal flora yeast Malassezia furfur (Pityrosporum ovale). Indeed, clinical studies have shown that administration of antifungal agents correlates with an improved clinical condition. Almost all commercially available hair shampoos publicize that they contain some form of antifungal agent(s). However, few studies have been published in which antifungal activity of commercially available hair shampoos have been contrasted experimentally. In this study six commercially available shampoos (in the Philippines) were assessed for antifungal activity against a human (dandruff) isolate of M. furfur: (a) Head & Shoulders (Proctor & Gamble); (b) Gard Violet (Colgate-Palmolive); (c) Nizoral 1% (Janssen); (d) Nizoral 2% (Janssen); (e) Pantene Blue (Proctor & Gamble); and (f) Selsun Blue (Abbott). The results demonstrated that all six of the assayed hair shampoos have some antifungal effect on the test yeast. However, there was consider variation in potency of antifungal activity. Nizoral 1% and Nizoral 2% shampoo preparations were the most effective. The 1% Nizoral shampoo was consistently 10X better at killing yeast cells than the next closest rival shampoo. The 2% Nizoral shampoo was 10X better than the Nizoral 1% product and 100 times better than any of the other products assayed. The study demonstrated that shampoos containing a proven antifungal compound were the most effective in controlling the causative yeast.

Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species.

PubMed

Lackner, Michaela; de Hoog, G Sybren; Verweij, Paul E; Najafzadeh, Mohammad J; Curfs-Breuker, Ilse; Klaassen, Corné H; Meis, Jacques F

2012-05-01

Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (n = 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P. boydii (geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar susceptibility patterns, those for S. aurantiacum, S. prolificans, and S. dehoogii were different from each other. Voriconazole was the only drug with significant activity against S. aurantiacum isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of antifungal susceptibility difficult. Therefore, antifungal susceptibility testing of all clinical isolates remains essential for targeted antifungal therapy. Voriconazole was the only compound with low MIC values (MIC(90) of ≤ 2 μg/ml) for P. apiosperma and P. boydii. Micafungin and posaconazole showed moderate activity against the majority of Scedosporium strains.

Species-Specific Antifungal Susceptibility Patterns of Scedosporium and Pseudallescheria Species

PubMed Central

Lackner, Michaela; de Hoog, G. Sybren; Verweij, Paul E.; Najafzadeh, Mohammad J.; Curfs-Breuker, Ilse; Klaassen, Corné H.

2012-01-01

Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (n = 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P. boydii (geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar susceptibility patterns, those for S. aurantiacum, S. prolificans, and S. dehoogii were different from each other. Voriconazole was the only drug with significant activity against S. aurantiacum isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of antifungal susceptibility difficult. Therefore, antifungal susceptibility testing of all clinical isolates remains essential for targeted antifungal therapy. Voriconazole was the only compound with low MIC values (MIC90 of ≤2 μg/ml) for P. apiosperma and P. boydii. Micafungin and posaconazole showed moderate activity against the majority of Scedosporium strains. PMID:22290955

Chemical composition and antifungal activity of Carica papaya Linn. seed essential oil against Candida spp.

PubMed

He, X; Ma, Y; Yi, G; Wu, J; Zhou, L; Guo, H

2017-05-01

In recent years, the incidence of clinical yeast infections has increased dramatically. Due to the extensive use of broad-spectrum antifungal agents, there has been a notable increase in drug resistance among infections yeast species. As one of the most popular natural antimicrobial agents, essential oils (EOs) have attracted a lot of attention from the scientific community. The aim of this study was to analyse the chemical composition and examine the antifungal activity of the EO extracted from the seeds of Carica papaya Linn. The papaya seed EO was analysed by gas chromatography-mass spectrometry. The major constituent is benzyl isothiocyanate (99·36%). The filter paper disc diffusion method and broth dilution method were employed. The EO showed inhibitory effect against all the tested Candida strains including C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropical with inhibition zone diameters in the range of 14·2-33·2 mm, the minimal inhibitory concentrations (MICs) in the range of 4·0-16·0 μg ml -1 and the minimum fungicidal concentrations (MFCs) in the range of 16·0-64·0 μg ml -1 . Here, we found that the papaya seed EO has promising anticandida activity and identify C. papaya L. as a potential natural source of antifungal agents. The chemical composition and antifungal activity of essential oil of Carica papaya seeds were studied. The oil of papaya seeds could inhibit the growth of Candida spp. for the first report. Carica Papaya may be recognized as a possible new source of natural antifungal agents. © 2017 The Society for Applied Microbiology.

Cryptic antifungal compounds active by synergism with polyene antibiotics.

PubMed

Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

2016-04-01

The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

USDA-ARS?s Scientific Manuscript database

Many pathogenic fungi are becoming resistant to currently available drugs. Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. The aim of this study was to identify benzaldehydes that...

Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study.

PubMed

Breda, Giovanni L; Tuon, Felipe F; Meis, Jacques F; Herkert, Patricia F; Hagen, Ferry; de Oliveira, Letícia Z; Dias, Viviane de Carvalho; da Cunha, Clóvis Arns; Queiroz-Telles, Flávio

2018-06-01

Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis. Sequential Candida isolates from BrC were identified by internal transcribed spacer sequencing, genotyped with amplified fragment length polymorphism fingerprinting (AFLP), and tested for antifungal susceptibility. From 148 candidemia episodes, 27 breakthrough episodes (18%) were identified, with neutropenia and mucositis being independent risk factors for BrC. Candida non-albicans was more frequent in the BrC group (P < .001). AFLP showed high correlation with conventional methods of identification among breakthrough isolates and a high genetic similarity among isolates from the same patient was observed. C. albicans was the most susceptible species with low MIC values for all antifungal agents tested. In contrast, we found isolates of C. glabrata, C. parapsilosis and C. tropicalis resistant to triazoles and echinocandins. In conclusion, BrC occurred mainly in severely immunosuppressed patients, with neutropenia and mucositis. Mortality did not differ between the groups. Candida non-albicans species were more recovered from BrC, with C. albicans being the most susceptible to antifungals.

Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.

PubMed

Bohnert, Markus; Nützmann, Hans-Wilhelm; Schroeckh, Volker; Horn, Fabian; Dahse, Hans-Martin; Brakhage, Axel A; Hoffmeister, Dirk

2014-09-01

The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antifungal Susceptibility Patterns of Opportunistic Fungi in the Genera Verruconis and Ochroconis

PubMed Central

Samerpitak, K.; Rijs, A. J. M. M.; Melchers, W. J. G.; Mouton, J. W.; Verweij, P. E.; de Hoog, G. S.

2014-01-01

Species of Verruconis and species of Ochroconis are dematiaceous fungi generally found in the environment but having the ability to infect humans, dogs, cats, poultry, and fish. This study presents the antifungal susceptibility patterns of these fungi at the species level. Forty strains originating from clinical and environmental sources were phylogenetically identified at the species level by using sequences of the ribosomal DNA internal transcribed spacer (rDNA ITS). In vitro antifungal susceptibility testing was performed against eight antifungals, using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. The geometric mean MICs for amphotericin B (AMB), flucytosine (5FC), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), and posaconazole (POS) and minimum effective concentrations (MECs) for caspofungin (CAS) and anidulafungin (AFG) across the Ochroconis and Verruconis species were as follows, in increasing order. For Verruconis species, the values (μg/ml) were as follows: AFG, 0.04; POS, 0.25; ITC, 0.37; AMB, 0.50; CAS, 0.65; VRC, 0.96; 5FC, 10.45; and FLC, 47.25. For Ochroconis species, the values (μg/ml) were as follows: AFG, 0.06; POS, 0.11; CAS, 0.67; VRC, 2.76; ITC, 3.94; AMB, 5.68; 5FC, 34.48; and FLC, 61.33. Antifungal susceptibility of Ochroconis and Verruconis was linked with phylogenetic distance and thermotolerance. Echinocandins and POS showed the greatest in vitro activity, providing possible treatment options for Ochroconis and Verruconis infections. PMID:24687495

Characterization of three antifungal calcite-forming bacteria, Arthrobacter nicotianae KNUC2100, Bacillus thuringiensis KNUC2103, and Stenotrophomonas maltophilia KNUC2106, derived from the Korean islands, Dokdo and their application on mortar.

PubMed

Park, Jong-Myong; Park, Sung-Jin; Ghim, Sa-Youl

2013-09-28

Crack remediation on the surface of cement mortar using microbiological calcium carbonate (CaCO3) precipitation (MICP) has been investigated as a microbial sealing agent on construction materials. However, MICP research has never acknowledged the antifungal properties of calcite-forming bacteria (CFB). Since fungal colonization on concrete surfaces can trigger biodeterioration processes, fungi on concrete buildings have to be prevented. Therefore, to develop a microbial sealing agent that has antifungal properties to remediate cement cracks without deteriorative fungal colonization, we introduced an antifungal CFB isolated from oceanic islands (Dokdo islands, territory of South Korea, located at the edge of the East Sea in Korea.). The isolation of CFB was done using B4 or urea-CaCl2 media. Furthermore, antifungal assays were done using the pairing culture and disk diffusion methods. Five isolated CFB showed CaCO3 precipitation and antifungal activities against deteriorative fungal strains. Subsequently, five candidate bacteria were identified using 16S rDNA sequence analysis. Crack remediation, fungi growth inhibition, and water permeability reduction of antifungal CFB-treated cement surfaces were tested. All antifungal CFB showed crack remediation abilities, but only three strains (KNUC2100, 2103, and 2106) reduced the water permeability. Furthermore, these three strains showed fungi growth inhibition. This paper is the first application research of CFB that have antifungal activity, for an eco-friendly improvement of construction materials.

Combination of fluconazole with non-antifungal agents: a promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery.

PubMed

Liu, Shuyuan; Hou, Yinglong; Chen, Xu; Gao, Yuan; Li, Hui; Sun, Shujuan

2014-05-01

The past decades have witnessed a dramatic increase in invasive fungal infections, especially candidiasis. Despite the development of more effective new antifungal agents, fluconazole (FLC) is still widely used in the clinic because of its efficacy and low toxicity. However, as the number of patients treated with FLC has increased, FLC-resistant Candida albicans isolates emerge more frequently. In addition, biofilm-associated infections are commonly encountered and their resistance poses a great challenge to antifungal treatment. Various approaches have been proposed to increase the susceptibility of C. albicans to FLC in order to cope with treatment failures, among which is the combination of FLC with different classes of non-antifungal agents such as antibacterials, calcineurin inhibitors, heat shock protein 90 inhibitors, calcium homeostasis regulators and traditional Chinese medicine drugs. Interestingly, many of these combinations showed synergistic effects against C. albicans, especially resistant strains. The main mechanisms of these synergistic effects appear to be increasing the permeability of the membrane, reducing the efflux of antifungal drugs, interfering with intracellular ion homeostasis, inhibiting the activity of proteins and enzymes required for fungal survival, and inhibiting biofilm formation. These modes of action and the antifungal mechanisms of various compounds referenced in this paper highlight the idea that the reversal of fungal resistance can be achieved through various mechanisms. Studies examining drug interactions will hopefully provide new approaches against antifungal drug resistance as well as insight into antifungal agent discovery. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

LC-MS and 1H NMR as an improved dereplication tool to identify antifungal diterpenoids from Sagittaria latifolia

USDA-ARS?s Scientific Manuscript database

A dereplication strategy using a combination of liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1H NMR) to facilitate compound identification towards antifungal natural product discovery is presented. This analytical approach takes advantage of th...

Caryolan-1-ol, an antifungal volatile produced by Streptomyces spp., inhibits the endomembrane system of fungi

USDA-ARS?s Scientific Manuscript database

Streptomyces spp. have the ability to produce a wide variety of secondary metabolites that interact with the environment. This study aimed to discover antifungal volatiles from the genus Streptomyces and to determine the mechanisms of inhibition. Volatiles identified from Streptomyces spp. included ...

Yeasts from Scarlet ibises (Eudocimus ruber): A focus on monitoring the antifungal susceptibility of Candida famata and closely related species.

PubMed

Brilhante, Raimunda Sâmia Nogueira; Silva, Aline Lobão da; Monteiro, Frederico Ozanan Barros; Guedes, Glaucia Morgana de Melo; Sales, Jamille Alencar; Oliveira, Jonathas Sales de; Maia Junior, José Erisvaldo; Miranda, Stefânia Araújo; Sidrim, José Júlio Costa; Alencar, Lucas Pereira de; Castelo-Branco, Débora Souza Collares Maia; Cordeiro, Rossana de Aguiar; Pereira Neto, Waldemiro de Aquino; Rocha, Marcos Fábio Gadelha

2017-10-01

This study aimed to identify yeasts from the gastrointestinal tract of scarlet ibises (Eudocimus ruber) and from plant material collected from the environment where they live. Then, the isolates phenotypically identified as Candida famata were submitted to molecular identification of their closely related species and evaluated for their antifungal susceptibility and possible resistance mechanisms to antifungal drugs. Cloacal swabs from 20 scarlet ibises kept in captivity at Mangal das Garças Park (Brazil), pooled stool samples (n = 20) and samples of trunks and hollow of trees (n = 20) obtained from their enclosures were collected. The samples were seeded on Sabouraud agar supplemented with chloramphenicol. The 48 recovered isolates were phenotypically identified as 15 Candida famata, 13 Candida catenulata, 2 Candida intermedia, 1 Candida lusitaniae, 2 Candida guilliermondii, 1 Candida kefyr, 1 Candida amapae, 1 Candida krusei, 8 Trichosporon spp., and 4 Rhodotorula spp. The C. famata isolates were further identified as 3 C. famata, 8 Debaryomyces nepalensis, and 4 C. palmioleophila. All C. famata and C. palmioleophila were susceptible to caspofungin and itraconazole, while one D. nepalensis was resistant to fluconazole and voriconazole. This same isolate and another D. nepalensis had lower amphotericin B susceptibility. The azole resistant strain had an increased efflux of rhodamine 6G and an alteration in the membrane sterol content, demonstrating multifactorial resistance mechanism. Finally, this research shows that scarlet ibises and their environment harbor C. famata and closely related species, including antifungal resistant isolates, emphasizing the need of monitoring the antifungal susceptibility of these yeast species. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Characterization and control of thread mould in cheese.

PubMed

Basílico, J C; debasílico, M Z; Chiericatti, C; Vinderola, C G

2001-06-01

The origin of a mould responsible for the contamination of an Argentinian cheese factory was identified and several antifungal treatments were assessed. Moulds were isolated and identified from vacuum-packed hard cheeses, from the environment and from the surfaces of the factory. A suspension conidia test containing different fungicides was performed; another assay involved the fumigation with p-OH fenilsalicidamide. Only Phoma glomerata was found in all of the mouldy cheeses, and was also obtained from different environments and machine surfaces. The most effective treatments against P. glomerata isolates were 0.5% (w/v) natamycin and 2% (v/v) parabens. Fumigation with p-OH fenilsalicidamide showed no satisfactory results. P. glomerata is an important thread mould-contaminating agent in vacuum-packed hard cheeses. Taking into account the survival of the conidia of the P. glomerata isolates to different antifungal treatments, the sources of contamination need to be controlled by designing a good factory layout.

Topical antifungal agents: an update.

PubMed

Diehl, K B

1996-10-01

So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.

Use of response surface methodology to evaluate the effect of metal ions (Ca2+, Ni2+, Mn2+, Cu2+) on production of antifungal compounds by Paenibacillus polymyxa.

PubMed

Raza, Waseem; Hongsheng, Wu; Qirong, Shen

2010-03-01

The effects of four metal ions (Ca(2+), Ni(2+), Mn(2+) and Cu(2+)) were evaluated on growth and production of antifungal compounds by Paenibacillus polymyxa SQR-21 and a quadratic predictive model was developed using response surface methodology (RSM). The results revealed, Mn(2+) and Ni(2+) showed most positive synergistic interactive affect on production of antifungal compounds followed by the positive interactive synergistic affect of Cu(2+) and Ni(2+) and then Mn(2+) and Cu(2+). While the interactive effect of Ca(2+) with all other three metals inhibited the production of antifungal compounds. The Mn(2+) (P=0.0384), Ni(2+) (P=0.0004) and Cu(2+) (P=0.0117) significantly affected the production of antifungal compounds while the effect of Ca(2+) (P=0.1851) was less significant. The maximum growth (OD(600)=1.55) was obtained at 500 (0), 125 (0), 100 (-2) and 37.5 (0) microM levels and the maximum size of inhibition zone (31 mm) was measured at 400 (-1), 150 (1), 400 (1) and 25 microM (-1) levels of Ca(2+), Mn(2+), Ni(2+) and Cu(2+), respectively. The RSM model provided an easy and effective way to determine the interactive effect of metal ions on production of antifungal compounds by P. polymyxa SQR-21 so that optimum media recipes can be developed to produce maximum amounts of antifungal compounds under laboratory and commercial fermentation conditions. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Selection of discrimination marker from various propolis for mapping and identify anti Candida albicans activity

NASA Astrophysics Data System (ADS)

Mahadewi, Alfiani Guntari; Christina, Daisy; Hermansyah, Heri; Wijanarko, Anondho; Farida, Siti; Adawiyah, Robiatul; Rohmatin, Etin; Sahlan, Muhamad

2018-02-01

The increase in fungal resistance against antifungal drugs available in the market will reduce the effectiveness of treatment for Candidiasis. Propolis contains various compounds with antifungal properties Candida albicans, but the content of each type is very diverse. The sample used was Sulawesi propolis type smooth (taken from inside the nest), rough (taken from outside the hive) and mix (a combination of both). Anti-C. albicans molecule marker is a marker compound for selecting propolis with the ability to overcome Candidiasis. The initial step was to test the levels of flavonoids and phenolic by using UV-Vis spectrometry method. It was founded that each sample was not always superior to any substance, so propolis cannot be directly selected. In Phenolic content, mix propolis has the highest value than other 5.109%. In Flavonoid content, propolis smooth has the highest value than other, 16.38%. Furthermore, propolis selected by antifungal activity test with good diffusion method at the concentration propolis 5% either 7%, the inhibitory diameter zone propolis smooth and rough has same value 10 mm. Propolis mix has an advantage while propolis smooth and rough have the same capability range 12 mm and 13 mm. In this study, the phenolic content plays a major role in antifungal cases.

NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning

PubMed Central

Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

2016-01-01

Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans.

PubMed

Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

2015-01-01

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections.

Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

PubMed

Fung, Monica; Kim, Jane; Marty, Francisco M; Schwarzinger, Michaël; Koo, Sophia

2015-01-01

Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines

PubMed Central

Cotesta, Simona; Perruccio, Francesca; Knapp, Britta; Fu, Yue; Studer, Christian; Pries, Verena; Riedl, Ralph; Helliwell, Stephen B.; Petrovic, Katarina T.; Movva, N. Rao; Sanglard, Dominique; Tao, Jianshi; Hoepfner, Dominic

2016-01-01

Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point. PMID:27855158

Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.

PubMed

Li, Xing-Cong; Joshi, Alpana S; ElSohly, Hala N; Khan, Shabana I; Jacob, Melissa R; Zhang, Zhizheng; Khan, Ikhlas A; Ferreira, Daneel; Walker, Larry A; Broedel, Sheldon E; Raulli, Robert E; Cihlar, Ronald L

2002-12-01

Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.

Biocontrol of Aspergillus Species on Peanut Kernels by Antifungal Diketopiperazine Producing Bacillus cereus Associated with Entomopathogenic Nematode

PubMed Central

Kumar, Sasidharan Nishanth; Sreekala, Sreerag Ravikumar; Chandrasekaran, Dileep; Nambisan, Bala; Anto, Ruby John

2014-01-01

The rhabditid entomopathogenic nematode associated Bacillus cereus and the antifungal compounds produced by this bacterium were evaluated for their activity in reducing postharvest decay of peanut kernels caused by Aspergillus species in in vitro and in vivo tests. The results showed that B. cereus had a significant effect on biocontrol effectiveness in in vitro and in vivo conditions. The antifungal compounds produced by the B. cereus were purified using silica gel column chromatography and their structure was elucidated using extensive spectral analyses. The compounds were identified as diketopiperazines (DKPs) [cyclo-(L-Pro-Gly), cyclo(L-Tyr-L-Tyr), cyclo-(L-Phe-Gly) and cyclo(4-hydroxy-L-Pro-L-Trp)]. The antifungal activities of diketopiperazines were studied against five Aspergillus species and best MIC of 2 µg/ml was recorded against A. flavus by cyclo(4-hydroxy-L-Pro-L-Trp). To investigate the potential application of cyclo(4-hydroxy-L-Pro-L-Trp) to eliminate fungal spoilage in food and feed, peanut kernels was used as a food model system. White mycelia and dark/pale green spores of Aspergillus species were observed in the control peanut kernels after 2 days incubation. However the fungal growth was not observed in peanut kernels treated with cyclo(4-hydroxy-L-Pro-L-Trp). The cyclo(4-hydroxy-L-Pro-L-Trp) was nontoxic to two normal cell lines [fore skin (FS) normal fibroblast and African green monkey kidney (VERO)] up to 200 µg/ml in MTT assay. Thus the cyclo(4-hydroxy-L-Pro-L-Trp) identified in this study may be a promising alternative to chemical preservatives as a potential biopreservative agent which prevent fungal growth in food and feed. To the best of our knowledge, this is the first report demonstrating that the entomopathogenic nematode associated B. cereus and cyclo(4-hydroxy-L-Pro-L-Trp) could be used as a biocontrol agents against postharvest fungal disease caused by Aspergillus species. PMID:25157831

Large-Scale Identification and Analysis of Suppressive Drug Interactions

PubMed Central

Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P.

2014-01-01

SUMMARY One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

Biotechnological production of inducible defense-related proteins in edible radish (raphanus sativus) found in Nepal.

PubMed

Khanal, Praval; Karmacharya, Anil; Sharma, Shishir; Nepal, Ashwini K; Shrestha, Kanti

2014-01-01

Fungal infection in plant leads to use of many hazardous antifungal chemicals. Alternative to these chemicals, defense related antifungal proteins can be used in case of fungal diseases. An experiment was done in two varieties of edible radish (Raphanus sativus var. Pyuthane Raato and Raphanus sativus var. all season) with aims to produce defense protein within the plant, to identify and perform molecular characterization of those antifungal proteins. The next aim was to compare the antifungal property of those proteins with commercially available synthetic pesticides. Both varieties of radish were infected with fungi (Alternaria alternata and Fusarium oxysporum). Protein samples were isolated from leaves following the standard protocol as described for β-glucuronidase (GUS) assay and were run along with the standard protein marker of 10-250kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify and molecularly characterize them. An additional band in the range of 37-50kDa was observed in the fungal infected samples, which was not seen on uninfected samples. The antifungal assay was carried out for every sample in 96 wells microtitre plate. The extracted protein samples from fungal inoculated plants showed the significant inhibition of fungal growth compared to other samples. On the basis of molecular weight and their antifungal properties, the protein samples from the fungal infected plant were found to be PR2 (Glucanase) and PR3 (Chitinase). Defense related proteins were successfully produced in two varieties of radish found in Nepal. The use of such biologically produced proteins may reduce the use of biologically harmful synthetic pesticides.

Tinea of vellus hair: an indication for systemic antifungal therapy.

PubMed

Gómez-Moyano, E; Crespo-Erchiga, V

2010-09-01

Topical antifungal treatment is indicated in tinea of glabrous skin, except in cases of extensive, multiple or recurrent lesions, or immunocompromised patients. However, in daily practice there are cases resistant to topical treatment despite these indications. Parasitism of the hair could be the cause behind the majority of isolated lesions of ringworm of hairless skin with a poor outcome with topical antifungal treatment. To present a prospective observational study of 13 cases of tinea of glabrous skin with topical antifungal resistance during the period 2007-2009. Cases were analysed from a clinical, mycological and therapeutic standpoint. The mean age was 7 years. Eight (62%) patients reported prior contact with an animal and 10 (77%) patients had received topical corticosteroids before visiting the dermatologist. Excoriation was observed in eight (62%) patients, and follicular micropustules were seen in 11 (85%). In all patients, some short thin hairs fell easily on to the slide during the skin scraping. In all patients all the few vellus hairs identified in direct examination were affected. All identified species were zoophilic or geophilic. All cases resolved after oral antifungal treatment. In tinea of glabrous skin with low response to topical antifungal treatment we must rule out tinea of the vellus hair. Infection by nonanthropophilic dermatophytes, previous corticosteroid therapy and excoriation might be predisposing factors. Parasitism of the vellus hair, observed by direct microscopy, should be another criterion for establishing systemic treatment from the onset, as is the case in tinea capitis. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Characterization of fungal antagonistic bacilli isolated from aerial roots of banyan (Ficus benghalensis) using intact-cell MALDI-TOF mass spectrometry (ICMS).

PubMed

Pathak, K V; Keharia, H

2013-05-01

To characterize fungal antagonistic bacilli isolated from aerial roots of banyan tree and identify the metabolites responsible for their antifungal activity. Seven gram positive, endospore-forming, rod-shaped endophytic bacterial strains exhibiting a broad-spectrum antifungal activity were isolated from the surface-sterilized aerial roots of banyan tree. The isolates designated as K1, A2, A4 and A12 were identified as Bacillus subtilis, whereas isolates A11 and A13 were identified as Bacillus amyloliquefaciens using Biolog Microbial Identification System. The antifungal lipopeptides, surfactins, iturins and fengycins with masses varying in the range from m/z 900 to m/z 1550 could be detected using intact-cell MALDI-TOF mass spectrometry (ICMS). On the basis of mass spectral and carbon source utilization profile, all seven endophytes could be distinguished from each other. Furthermore, ICMS analysis revealed higher extent of heterogeneity among iturins and fengycins produced by B. subtilis K1, correlating well with its higher antifungal activity in comparison with other isolates. Seven fungal antagonistic bacilli were isolated from aerial roots of banyan tree, exhibiting broad spectrum of antifungal activity, among which B. subtilis K1 isolate was found to be most potent. The ICMS analysis revealed that all these isolates produced cyclic lipopeptides belonging to surfactin, iturin and fengycin families and exhibited varying degree of heterogeneity. The endophytes are considered as a potential source of novel bioactive metabolites, and this study describes the potent fungal antagonistic bacilli from aerial roots of banyan tree. The isolates described in this study have a prospective application as biocontrol agents. Also ICMS analysis described in this study for characterization of antifungal metabolites produced by banyan endophytic bacilli may be used as a high throughput tool for screening of microbes producing novel cyclic lipopeptides. © 2013 The Society for Applied Microbiology.

Antifungal and antimycotoxigenic metabolites in Anacardiaceae species from northwest Argentina: isolation, identification and potential for control of Fusarium species.

PubMed

Aristimuño Ficoseco, M E; Vattuone, M A; Audenaert, K; Catalán, C A N; Sampietro, D A

2014-05-01

The purpose of this research was to identify antifungal compounds from leaves of Schinus and Schinopsis species useful for the control of toxigenic Fusarium species responsible of ear rot diseases. Leaves of Schinopsis (S. lorentzii and S. haenkeana) and Schinus (S. areira, S. gracilipes and S. fasciculatus) were sequentially extracted with dichloromethane, ethyl acetate and methanol. The antifungal activity of the fraction soluble in methanol of these extracts (fCH2Cl2, fAcEt and fMeOH, respectively) was determined by the broth microdilution method and the disc-diffusion method. The minimum inhibitory dose (MID), the diameter of growth inhibition (DGI) and the minimum concentration for 50% inhibition of fungal growth (MIC50) were calculated. The fCH2Cl2 and fAcEt of the Schinopsis species had the lowest MID and MIC50 values and the highest DGI. The antifungal compounds were identified as lupeol and a mix of phenolic lipids. The last one had the highest antifungal activity with MIC50 31-28 μg g(-1) and 165-150 μg g(-1) on Fusarium graminearum and Fusarium verticillioides, respectively. The identified metabolites completely inhibited fumonisin and deoxynivalenol production at lower concentrations than ferulic acid, a natural antimycotoxigenic compound. It was proven that lupeol and phenolic lipids were inhibitors of both fungal growth and mycotoxin production of toxigenic Fusarium species. This fact is specially interesting in the control of the toxigenic Fusarium species because several commercial antifungals showed to stimulate mycotoxin biosynthesis at sublethal concentrations. Control of toxigenic Fusarium species requires compounds able to inhibit both fungal growth and mycotoxin production. Our results suggest that the use of lupeol as food preservative and the phenolic lipids as fungal growth inhibitors of F. verticillioides and F. graminearum did not imply an increase in mycotoxin accumulation. © 2014 The Society for Applied Microbiology.

Direct comparison of the pharmacodynamics of four antifungal drugs in a mouse model of disseminated candidiasis using microbiological assays of serum drug concentrations.

PubMed

Maki, Katsuyuki; Holmes, Ann R; Watabe, Etsuko; Iguchi, Yumi; Matsumoto, Satoru; Ikeda, Fumiaki; Tawara, Shuichi; Mutoh, Seitaro

2007-01-01

The aim of this study was to compare the pharmacodynamics of the azole antifungal drugs fluconazole, itraconazole and ketoconazole, and the polyene antifungal amphotericin B, in a mouse model of disseminated Candida albicans infection. In order to directly compare effective serum concentrations of these antifungals, drug concentrations were assayed microbiologically by measuring inhibition of C. albicans mycelial growth (mMIC) in a mouse serum-based assay (serum antifungal titer). Efficacy in the mouse infection model was determined using an organ-based (kidney burden) endpoint. For all four drugs, the serum antifungal titers, 8 hr after administration of single doses of drugs at a range of drug concentrations, correlated closely with C. albicans kidney fungal burden in the mouse model. The results showed that determining serum antifungal titer may be used to accurately represent kidney fungal burden in a mouse model of disseminated candidiasis and allowed direct comparison of the pharmacodynamics of differing classes of antifungal drugs.

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

PubMed Central

Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

2015-01-01

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections. PMID:26048362

Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark extracts

PubMed Central

Nariya, Pankaj B.; Bhalodia, Nayan R.; Shukla, V. J.; Acharya, R. N.

2011-01-01

Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in Ayurvedic pharmacopoeias. Present study was carried out with an objective to investigate the antibacterial and antifungal potentials of Cordia dichotoma bark. Antibacterial activity of methanol and butanol extracts of the bark was carried out against two gram negative bacteria (Escherichia coli, and Pseudomonas aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus aureus). The antifungal activity of the extracts was carried out against three common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans). Zone of inhibition of extracts was compared with that of different standards like Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial activity and Nystain and Greseofulvin for antifungal activity. The extracts showed remarkable inhibition of zone of bacterial growth and fungal growth and the results obtained were comparable with that of standards drugs against the organisms tested. The activity of extracts increased linearly with increase in concentration of extract (mg/ml). The results showed the antibacterial and antifungal activity against the organisms tested. PMID:22661859

Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark extracts.

PubMed

Nariya, Pankaj B; Bhalodia, Nayan R; Shukla, V J; Acharya, R N

2011-10-01

Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in Ayurvedic pharmacopoeias. Present study was carried out with an objective to investigate the antibacterial and antifungal potentials of Cordia dichotoma bark. Antibacterial activity of methanol and butanol extracts of the bark was carried out against two gram negative bacteria (Escherichia coli, and Pseudomonas aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus aureus). The antifungal activity of the extracts was carried out against three common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans). Zone of inhibition of extracts was compared with that of different standards like Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial activity and Nystain and Greseofulvin for antifungal activity. The extracts showed remarkable inhibition of zone of bacterial growth and fungal growth and the results obtained were comparable with that of standards drugs against the organisms tested. The activity of extracts increased linearly with increase in concentration of extract (mg/ml). The results showed the antibacterial and antifungal activity against the organisms tested.

Chemical Composition and Antifungal Activity of Ocimum basilicum L. Essential Oil

PubMed Central

El-Soud, Neveen Helmy Abou; Deabes, Mohamed; El-Kassem, Lamia Abou; Khalil, Mona

2015-01-01

BACKGROUND: The leaves of Ocimum basilicum L. (basil) are used in traditional cuisine as spices; its essential oil has found a wide application in perfumery, dental products as well as antifungal agents. AIM: To assess the chemical composition as well as the in vitro antifungal activity of O. basilicum L. essential oil against Aspergillus flavus fungal growth and aflatoxin B1 production. MATERIAL AND METHODS: The essential oil of O. basilicum was obtained by hydrodistillation and analysed using gas chromatography (GC) and GC coupled with mass spectrometry (GC/MS). The essential oil was tested for its effects on Aspergillus flavus (A. flavus) mycelial growth and aflatoxin B1 production in Yeast Extract Sucrose (YES) growth media. Aflatoxin B1 production was determined by high performance liquid chromatography (HPLC). RESULTS: Nineteen compounds, representing 96.7% of the total oil were identified. The main components were as follows: linalool (48.4%), 1,8-cineol (12.2%), eugenol (6.6%), methyl cinnamate (6.2%), α-cubebene (5.7%), caryophyllene (2.5%), β-ocimene (2.1%) and α-farnesene (2.0%). The tested oil showed significant antifungal activity that was dependent on the used oil concentration. The complete inhibition of A. flavus growth was observed at 1000 ppm oil concentration, while marked inhibition of aflatoxin B1 production was observed at all oil concentrations tested (500, 750 and 1000 ppm). CONCLUSION: These results confirm the antifungal activities of O. basilicum L. oil and its potential use to cure mycotic infections and act as pharmaceutical preservative against A. flavus growth and aflatoxin B1 production. PMID:27275253

Antifungal effect and pore-forming action of lactoferricin B like peptide derived from centipede Scolopendra subspinipes mutilans.

PubMed

Choi, Hyemin; Hwang, Jae-Sam; Lee, Dong Gun

2013-11-01

The centipede Scolopendra subspinipes mutilans has been a medically important arthropod species by using it as a traditional medicine for the treatment of various diseases. In this study, we derived a novel lactoferricin B like peptide (LBLP) from the whole bodies of adult centipedes, S. s. mutilans, and investigated the antifungal effect of LBLP. LBLP exerted an antifungal and fungicidal activity without hemolysis. To investigate the antifungal mechanism of LBLP, a membrane study with propidium iodide was first conducted against Candida albicans. The result showed that LBLP caused fungal membrane permeabilization. The assays of the three dimensional flow cytometric contour plot and membrane potential further showed cell shrinkage and membrane depolarization by the membrane damage. Finally, we confirmed the membrane-active mechanism of LBLP by synthesizing model membranes, calcein and FITC-dextran loaded large unilamellar vesicles. These results showed that the antifungal effect of LBLP on membrane was due to the formation of pores with radii between 0.74nm and 1.4nm. In conclusion, this study suggests that LBLP exerts a potent antifungal activity by pore formation in the membrane, eventually leading to fungal cell death. © 2013.

Effective concentration-based serum pharmacodynamics for antifungal azoles in a murine model of disseminated Candida albicans infection.

PubMed

Maki, Katsuyuki; Kaneko, Shuji

2013-12-01

An assessment of the effective in vivo concentrations of antifungal drugs is important in determining their pharmacodynamics, and therefore, their optimal dosage regimen. Here we establish the effective in vivo concentration-based pharmacodynamics of three azole antifungal drugs (fluconazole, itraconazole, and ketoconazole) in a murine model of disseminated Candida albicans infection. A key feature of this study was the use of a measure of mycelial (m) growth rather than of yeast growth, and pooled mouse sera rather than synthetic media as a growth medium, for determining the minimum inhibitory concentrations (MICs) of azoles for C. albicans (denoted serum mMICs). The serum mMIC assay was then used to measure antifungal concentrations and effects as serum antifungal titers in the serum of treated mice. Both serum mMIC and sub-mMIC values reflected the effective in vivo serum concentrations. Supra-mMIC and mMIC effects exhibited equivalent efficacies and were concentration-independent, while the sub-mMIC effect was concentration-dependent. Following administration of the minimum drug dosage that inhibited an increase in mouse kidney fungal burden, the duration periods of these effects were similar for all drugs tested. The average duration of either the mMIC effect including the supra-mMIC effect, the sub-mMIC effect, or the post-antifungal effect (PAFE) were 6.9, 6.5 and 10.6 h, respectively. Our study suggests that the area under the curve for serum drug concentration versus time, between the serum mMIC and the sub-mMIC, and exposure time above the serum sub-mMIC after the mMIC effect, are major pharmacodynamic parameters. These findings have important implications for effective concentration-based pharmacodynamics of fungal infections treated with azoles.

Impact of the antifungal protein PgAFP from Penicillium chrysogenum on the protein profile in Aspergillus flavus.

PubMed

Delgado, Josué; Owens, Rebecca A; Doyle, Sean; Asensio, Miguel A; Núñez, Félix

2015-10-01

Antifungal proteins produced by molds are generally small, highly basic, and cysteine-rich. The best known effects of these proteins include morphological changes, metabolic inactivation, and membrane perturbation on sensitive fungi. Reactive oxygen species (ROS) generation leads to apoptosis, with G -protein playing a key role in transduction of cell death signals. The antifungal protein PgAFP from Penicillium chrysogenum inhibits growth of some toxigenic molds. Here we analyzed the effect of the antifungal protein PgAFP on the growth of Aspergillus flavus. For this, comparative proteomic analysis was used to identify the whole protein profile and protein change in abundance after PgAFP treatment. PgAFP provoked metabolic changes related to reduced energy metabolism, cell wall integrity alteration, and increased stress response due to higher levels of ROS. The observed changes in protein abundance, favoring a higher glutathione concentration as well as the increased abundance in heat shock proteins, do not seem to be enough to avoid necrosis. The decreased chitin deposition observed in PgAFP-treated A. flavus is attributed to a lower relative quantity of Rho1. The reduced relative abundance of a β subunit of G -protein seems to be the underlying reason for modulation of apoptosis in PgAFP-treated A. flavus hyphae. We propose Rho1 and G -protein subunit β CpcB to be the main factors in the mode of action of PgAFP in A. flavus. Additionally, enzymes essential for the biosynthesis of aflatoxin were no longer detectable in A. flavus hyphae at 24 h, following treatment with PgAFP. This presents a promising effect of PgAFP, which may prevent A. flavus from producing mycotoxins. However, the impact of PgAFP on actual aflatoxin production requires further study.

Antifungal activities of Hedychium essential oils and plant extracts against mycotoxigenic fungi

USDA-ARS?s Scientific Manuscript database

Plant-derived antifungal compounds are preferred to chemicals to reduce the risk of toxic effects on humans, livestock and the environment. Essential oil extracted from rhizomes and plant extracts of ornamental ginger lily (Hedychium spp.) were evaluated for their antifungal activity against two fu...

Diversity and antifungal activity of the endophytic fungi associated with the native medicinal cactus Opuntia humifusa (Cactaceae) from the United States

USDA-ARS?s Scientific Manuscript database

The endophytic fungal community associated with the native cactus Opuntia humifusa in the United States was investigated and its potential for providing antifungal compounds. A total of 108 endophytic fungal isolates were obtained and identified by molecular methods into 17 different taxa of the gen...

Antifungal activity of Morinda citrifolia fruit extract against Candida albicans.

PubMed

Jainkittivong, Aree; Butsarakamruha, Tassanee; Langlais, Robert P

2009-09-01

The objective of the study was to investigate the antifungal activity of Morinda citrifolia fruit extract on Candida albicans. Juice extract from M. citrifolia fruit was lyophilized and used in antifungal testing. Antifungal activity of M. citrifolia fruit extract against C. albicans was tested in vitro at various concentrations and for different contact times. The inhibitory effect of M. citrifolia extract on C. albicans was determined by cultures and an applied broth dilution test. Using cultures, growth of C. albicans was not detected with 50 mg/mL of extract at 30-minute contact time or with 60 mg/mL of extract at 15-minute contact time. By the broth dilution test, the minimum fungicidal concentration of extract against C. albicans was 40 mg/mL at 90-minute contact time or with 50 mg/mL at 15-minute contact time. M. citrifolia fruit extract had an antifungal effect on C. albicans and the inhibitory effect varied with concentration and contact time.

The antifungal effect of silver nanoparticles on Trichosporon asahii.

PubMed

Xia, Zhi-Kuan; Ma, Qiu-Hua; Li, Shu-Yi; Zhang, De-Quan; Cong, Lin; Tian, Yan-Li; Yang, Rong-Ya

2016-04-01

Silver nanoparticles are receiving increasing attention in biomedical applications. This study aims at evaluating the antifungal properties of silver nanoparticles against the pathogenic fungus Trichosporon asahii. The growth of T. asahii on potato dextrose agar medium containing different concentrations of silver nanoparticles was examined and the antifungal effect was evaluated using minimum inhibitory concentration. Scanning and transmission electron microscopy were also used to investigate the antifungal effect of silver nanoparticles on T. asahii. Silver nanoparticles had a significant inhibitory effect on the growth of T. asahii. The minimum inhibitory concentration of silver nanoparticles against T. asahii was 0.5 μg/mL, which was lower than amphotericin B, 5-flucytosine, caspofungin, terbinafine, fluconazole, and itraconazole and higher than voriconazole. Silver nanoparticles obviously damaged the cell wall, cell membrane, mitochondria, chromatin, and ribosome. Our results demonstrate that silver nanoparticles have good antifungal activity against T. asahii. Based on our electron microscopy observations, silver nanoparticles may inhibit the growth of T. asahii by permeating the fungal cell and damaging the cell wall and cellular components. Copyright © 2014. Published by Elsevier B.V.

Isolation and antifungal activity of 4-phenyl-3-butenoic acid from Streptomyces koyangensis strain VK-A60.

PubMed

Lee, Jee Yeon; Lee, Jung Yeop; Moon, Surk Sik; Hwang, Byung Kook

2005-10-05

An antifungal compound was isolated from the culture broth of Streptomyces koyangensis strain VK-A60 using various chromatographic procedures. On the basis of the high-resolution EI-mass and 1H and 13C NMR data, the compound was identified as 4-phenyl-3-butenoic acid. Colletotrichum orbiculare, Magnaporthe grisea, and Pythium ultimum were most sensitive to 4-phenyl-3-butenoic acid. Strong inhibitory effects of 4-phenyl-3-butenoic acid also were found against Pectobacterium carotovorum subsp. carotovorum and Ralstonia solanacearum. 4-Phenyl-3-butenoic acid effectively suppressed the development of M. grisea on rice leaves at the concentration of more than 10 microg/mL, and the protective activity was in general similar to that of the commercial fungicide tricyclazole. Treatment with 100 microg/mL of 4-phenyl-3-butenoic acid also effectively inhibited the anthracnose development on cucumber plants, although its in vivo efficacy was somewhat less effective than that of the commercial fungicide chlorothalonil.

Antifungal Therapy in Birds: Old Drugs in a New Jacket.

PubMed

Antonissen, Gunther; Martel, An

2018-05-01

The use of antifungals in birds is characterized by interspecies and interindividual variability in the pharmacokinetics, affecting drug safety and efficacy. Oral antifungal drug absorption is a complex process affected by drug formulation characteristics, gastrointestinal anatomy, and physiology. New antifungal drug delivery systems can enhance drug stability, reduce off-target side effects, prolong residence time in the blood, and improve efficacy. Topical administration of antifungals through nebulization shows promising results. However, therapeutic output is highly influenced by drug formulation and type of nebulizer, indicating these factors should be taken into account when selecting this medication route. Copyright © 2018 Elsevier Inc. All rights reserved.

Antifungal Activity of Wickerhamomyces anomalus and Lactobacillus plantarum during Sourdough Fermentation: Identification of Novel Compounds and Long-Term Effect during Storage of Wheat Bread ▿

PubMed Central

Coda, Rossana; Cassone, Angela; Rizzello, Carlo G.; Nionelli, Luana; Cardinali, Gianluigi; Gobbetti, Marco

2011-01-01

This study aimed at investigating the antifungal activity of Wickerhamomyces anomalus and sourdough lactic acid bacteria to extend the shelf life of wheat flour bread. The antifungal activity was assayed by agar diffusion, growth rate inhibition, and conidial germination assays, using Penicillium roqueforti DPPMAF1 as the indicator fungus. Sourdough fermented by Lactobacillus plantarum 1A7 (S1A7) and dough fermented by W. anomalus LCF1695 (D1695) were selected and characterized. The water/salt-soluble extract of S1A7 was partially purified, and several novel antifungal peptides, encrypted into sequences of Oryza sativa proteins, were identified. The water/salt-soluble extract of D1695 contained ethanol and, especially, ethyl acetate as inhibitory compounds. As shown by growth inhibition assays, both water/salt-soluble extracts had a large inhibitory spectrum, with some differences, toward the most common fungi isolated from bakeries. Bread making at a pilot plant was carried out with S1A7, D1695, or a sourdough started with a combination of both strains (S1A7-1695). Slices of the bread manufactured with S1A7-1695 did not show contamination by fungi until 28 days of storage in polyethylene bags at room temperature, a level of protection comparable to that afforded by 0.3% (wt/wt) calcium propionate. The effect of sourdough fermentation with W. anomalus LCF1695 was also assessed based on rheology and sensory properties. PMID:21441340

Isolation of Bacteria with Antifungal Activity against the Phytopathogenic Fungi Stenocarpella maydis and Stenocarpella macrospora

PubMed Central

Petatán-Sagahón, Iván; Anducho-Reyes, Miguel Angel; Silva-Rojas, Hilda Victoria; Arana-Cuenca, Ainhoa; Tellez-Jurado, Alejandro; Cárdenas-Álvarez, Isabel Oyuki; Mercado-Flores, Yuridia

2011-01-01

Stenocarpella maydis and Stenocarpella macrospora are the causal agents of ear rot in corn, which is one of the most destructive diseases in this crop worldwide. These fungi are important mycotoxin producers that cause different pathologies in farmed animals and represent an important risk for humans. In this work, 160 strains were isolated from soil of corn crops of which 10 showed antifungal activity against these phytopathogens, which, were identified as: Bacillus subtilis, Pseudomonas spp., Pseudomonas fluorescens, and Pantoea agglomerans by sequencing of 16S rRNA gene and the phylogenetic analysis. From cultures of each strain, extracellular filtrates were obtained and assayed to determine antifungal activity. The best filtrates were obtained in the stationary phase of B. subtilis cultures that were stable to the temperature and extreme pH values; in addition they did not show a cytotoxicity effect against brine shrimp and inhibited germination of conidia. The bacteria described in this work have the potential to be used in the control of white ear rot disease. PMID:22016606

[In vitro activity of voriconazole and three other antifungal agents against dermatophytes].

PubMed

Serrano-Martino, María del Carmen; Chávez-Caballero, Mónica; Valverde-Conde, Anastasio; Claro, Rosa María; Pemán, Javier; Martín-Mazuelos, Estrella

2003-11-01

The increase in infections due to dermatophytes in recent years led us to study the effectiveness of new antifungal formulations against these microorganisms. The in vitro activity of a new antifungal agent, voriconazole, was compared with three other antifungal agents, itraconazole, fluconazole and terbinafine, against 120 dermatophytes belonging to four species (61 Trichophyton mentagrophytes, 34 Microsporum canis, 13 M. gypseum and 12 T. rubrum). A broth microdilution method was used following the recommendations of the NCCLS document M38-P with some modifications. Terbinafine was the most active agent against the dermatophytes studied (MIC90 < or = 0.03 mg/ml), followed by voriconazole (MIC90, 0.25 micro g/ml) and itraconazole (MIC90, 0.5 micro g/ml). Fluconazole was the least active antifungal agent. The most susceptible species was M. canis. Voriconazole was found to have effective activity against dermatophytes.

Antibacterial, antifungal, antispasmodic and Ca++ antagonist effects of Caesalpinia bonducella.

PubMed

Khan, Hidayat-Ullah; Ali, Irshad; Khan, Arif-Ullah; Naz, Rubina; Gilani, Anwarul Hassan

2011-02-01

Caesalpinia bonducella F. (Leguminosae) has been used as a folk medicine for a variety of ailments. The crude extract of C. bonducella and its fractions were studied for antibacterial, antifungal, antispasmodic and Ca++ antagonistic properties. The strongest antibacterial effect was displayed by the n-butanol (72%) and ethyl acetate (80%) fractions, followed by the crude extract (46% and 42%), against Escherichia coli and Bacillus subtilis, respectively. The plant extract and its fractions showed mild to excellent activity in antifungal bioassays, with maximum antifungal activity against Candida glaberata (80%) and Aspergillus flavus (70%) by the n-butanol and chloroform fractions, followed by the crude extract (70% and 65%). Caesalpinia bonducella extract caused concentration-dependent inhibition of spontaneous and high K+ (80 mM)-induced contractions of isolated rabbit jejunum preparations, similar to that caused by Verapamil. These results indicate that C. bonducella exhibits antibacterial, antifungal, spasmolytic and Ca++ channel blocking actions.

Targeting efflux pumps to overcome antifungal drug resistance

PubMed Central

Holmes, Ann R; Cardno, Tony S; Strouse, J Jacob; Ivnitski-Steele, Irena; Keniya, Mikhail V; Lackovic, Kurt; Monk, Brian C; Sklar, Larry A; Cannon, Richard D

2016-01-01

Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps. PMID:27463566

Biotechnological Production of Inducible Defense-Related Proteins in Edible Radish (Raphanus Sativus) Found in Nepal

PubMed Central

Khanal, Praval; Karmacharya, Anil; Sharma, Shishir; Nepal, Ashwini K.; Shrestha, Kanti

2014-01-01

Background: Fungal infection in plant leads to use of many hazardous antifungal chemicals. Alternative to these chemicals, defense related antifungal proteins can be used in case of fungal diseases. Aims: An experiment was done in two varieties of edible radish (Raphanus sativus var. Pyuthane Raato and Raphanus sativus var. all season) with aims to produce defense protein within the plant, to identify and perform molecular characterization of those antifungal proteins. The next aim was to compare the antifungal property of those proteins with commercially available synthetic pesticides. Methods: Both varieties of radish were infected with fungi (Alternaria alternata and Fusarium oxysporum). Protein samples were isolated from leaves following the standard protocol as described for β-glucuronidase (GUS) assay and were run along with the standard protein marker of 10-250kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify and molecularly characterize them. Results: An additional band in the range of 37-50kDa was observed in the fungal infected samples, which was not seen on uninfected samples. The antifungal assay was carried out for every sample in 96 wells microtitre plate. The extracted protein samples from fungal inoculated plants showed the significant inhibition of fungal growth compared to other samples. On the basis of molecular weight and their antifungal properties, the protein samples from the fungal infected plant were found to be PR2 (Glucanase) and PR3 (Chitinase). Conclusion: Defense related proteins were successfully produced in two varieties of radish found in Nepal. The use of such biologically produced proteins may reduce the use of biologically harmful synthetic pesticides. PMID:24596739

Effects of lactoferricin B against keratitis-associated fungal biofilms.

PubMed

Sengupta, Jayangshu; Saha, Suman; Khetan, Archana; Sarkar, Sujoy K; Mandal, Santi M

2012-10-01

Biofilms are considered as the most important developmental characteristics in ocular infections. Biofilm eradication is a major challenge today to overcome the incidence of drug resistance. This report demonstrates the in vitro ability of biofilm formation on contact lens by three common keratitis-associated fungal pathogens, namely, Aspergillus fumigatus, Fusarium solani, and Candida albicans. Antifungal sensitivity testing performed for both planktonic cells and biofilm revealed the sessile phenotype to be resistant at MIC levels for the planktonic cells and also at higher concentrations. A prototype lens care solution was also found to be partially effective in eradication of the mature biofilm from contact lenses. Lactoferricin B (Lacf, 64 μg/ml), an antimicrobial peptide, exhibited almost no effect on the sessile phenotype. However, the combinatory effect of Lacf with antifungals against planktonic cells and biofilms of three fungal strains that were isolated from keratitis patients exhibited a reduction of antifungal dose more than eightfold. Furthermore, the effect of Lacf in lens care solution against biofilms in which those strains formed was eradicated successfully. These results suggest that lactoferricin B could be a promising candidate for clinical use in improving biofilm susceptibility to antifungals and also as an antibiofilm-antifungal additive in lens care solution.

Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil.

PubMed

Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

2008-01-01

This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested.

Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil

PubMed Central

Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

2008-01-01

This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested. PMID:24031180

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

PubMed

Li, Ji-Xin; Li, Qi-Ji; Guan, Yi-Fu; Song, Xun; Liu, Ya-Hua; Zhang, Jing-Jie; Li, Wan-Fei; Du, Jiang; Zhu, Min; Banas, Jeffrey A; Li, Xiao-Nian; Pan, Lu-Tai; Zhang, Hong-Jie

2016-09-15

Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8μg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5μg/mL. Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

D19S Mutation of the Cationic, Cysteine-Rich Protein PAF: Novel Insights into Its Structural Dynamics, Thermal Unfolding and Antifungal Function

PubMed Central

Burtscher, Laura; Hajdu, Dorottya; Muñoz, Alberto; Gáspári, Zoltán; Read, Nick D.; Batta, Gyula; Marx, Florentine

2017-01-01

The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research. To understand its mode of action, we started to investigate the surface-exposed loops of PAF and replaced one aspartic acid at position 19 in loop 2 that is potentially involved in PAF active or binding site, with a serine (Asp19 to Ser19). We analysed the overall effects, such as unfolding, electrostatic changes, sporadic conformers and antifungal activity when substituting this specific amino acid to the fairly indifferent amino acid serine. Structural analyses revealed that the overall 3D solution structure is virtually identical with that of PAF. However, PAFD19S showed slightly increased dynamics and significant differences in the surface charge distribution. Thermal unfolding identified PAFD19S to be rather a two-state folder in contrast to the three-state folder PAF. Functional comparison of PAFD19S and PAF revealed that the exchange at residue 19 caused a dramatic loss of antifungal activity: the binding and internalization of PAFD19S by target cells was reduced and the protein failed to trigger an intracellular Ca2+ response, all of which are closely linked to the antifungal toxicity of PAF. We conclude that the negatively charged residue Asp19 in loop 2 is essential for full function of the cationic protein PAF. PMID:28072824

Effect of nagilactone E on cell morphology and glucan biosynthesis in budding yeast Saccharomyces cerevisiae.

PubMed

Hayashi, Kengo; Yamaguchi, Yoshihiro; Ogita, Akira; Tanaka, Toshio; Kubo, Isao; Fujita, Ken-Ichi

2018-05-14

Nagilactones are norditerpene dilactones isolated from the root bark of Podocarpus nagi. Although nagilactone E has been reported to show antifungal activities, its activity is weaker than that of antifungals on the market. Nagilactone E enhances the antifungal activity of phenylpropanoids such as anethole and isosafrole against nonpathogenic Saccharomyces cerevisiae and pathogenic Candida albicans. However, the detailed mechanisms underlying the antifungal activity of nagilactone E itself have not yet been elucidated. Therefore, we investigated the antifungal mechanisms of nagilactone E using S. cerevisiae. Although nagilactone E induced lethality in vegetatively growing cells, it did not affect cell viability in non-growing cells. Nagilactone E-induced morphological changes in the cells, such as inhomogeneous thickness of the glucan layer and leakage of cytoplasm. Furthermore, a dose-dependent decrease in the amount of newly synthesized (1, 3)-β-glucan was detected in the membrane fractions of the yeast incubated with nagilactone E. These results suggest that nagilactone E exhibits an antifungal activity against S. cerevisiae by depending on cell wall fragility via the inhibition of (1, 3)-β-glucan biosynthesis. Additionally, we confirmed nagilactone E-induced morphological changes of a human pathogenic fungus Aspergillus fumigatus. Therefore, nagilactone E is a potential antifungal drug candidate with fewer adverse effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw.

PubMed

Pereira, Flaviane G; Marquete, Ronaldo; Domingos, Levy T; Rocha, Marco E N; Ferreira-Pereira, Antonio; Mansur, Elisabeth; Moreira, Davyson L

2017-01-01

Casearia genus (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 160-200 species. It is a medicinal plant used in South America, also known as "guaçatonga", "erva-de-tiú", "cafezinho-do-mato". In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro, including Casearia sylvestris Sw. There are many studies related to the chemical profile and cytotoxic activities of extracts from these plants, although few studies about the antifungal potential of the essential oil have been reported. In this work, we have studied the antifungal properties of the essential oil of C. sylvestris leaves, as well as of their fractions, against four yeasts (Saccharomyces cerevisae, Candida albicans, C. glabrata and C. krusei) for the first time. The chemical analysis of the essential oil revealed a very diversified (n = 21 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). These sesquiterpenes included α-humulene (17.8%) and α-copaene (8.5%) and the oxygenated sesquiterpene spathulenol (11.8%) were also identified. Monoterpenes were not identified. The fractions are mainly composed of oxygenated sesquiterpenes, and the most active fraction is rich in the sesquiterpene 14-hydroxy -9-epi-β-caryophyllene. This fraction was the most effective in inhibiting the growth of three yeast strains.

In vitro antifungal activity of three geophytic plant extracts against three post-harvest pathogenic fungi.

PubMed

Maswada, Hanafey F; Abdallah, Sabry A

2013-12-01

Plant extracts appear to be one of the most effective alternative methods of plant diseases control which are less harmful to human beings and environment. In vitro antifungal activity of methanolic extracts of three promising wild geophytic plants against three post-harvest pathogenic fungi using radial growth technique was conducted. These extracts included the shoot system (S) and underground parts (R) of Asparagus stipularis, Cyperus capitatus and Stipagrostis lanata. The tested fungi were Alternaria solani, Aspergillus niger and Rhizopus stolonifer. The results exhibited that, all plant extracts had antifungal activity against the tested fungi. The antifungal activity greatly varied depending on plant parts and/or plant species. R. stolonifer was the most susceptible fungus to the tested plant extracts followed by A. niger and then A. solani. On the other hand, the most effective plant extracts against tested fungi were S. lanata (S) and A. stipularis (R). The most effective plant extracts against R. stolonifer were S. lanata (R) and C. capitatus (S). While, the extracts of A. stipularis (R) and S. lanata (S) were the most effective against A. niger. The extracts of C. capitatus (S) and S. lanata (S) exhibited the highest antifungal activity against A. solani. The results demonstrated that, the methanolic extracts of A. stipularis, C. capitatus and S. lanata had potential antifungal activity against A. solani, A. niger and R. stolonifer.

Activity of Posaconazole and Other Antifungal Agents against Mucorales Strains Identified by Sequencing of Internal Transcribed Spacers▿

PubMed Central

Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

2009-01-01

The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates. PMID:19171801

Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers.

PubMed

Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

2009-04-01

The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates.

An in vitro study of antifungal drug susceptibility of Candida species isolated from human immunodeficiency virus seropositive and human immunodeficiency virus seronegative individuals in Lucknow population Uttar Pradesh.

PubMed

Dar, Mohammad Shafi; Sreedar, Gadiputi; Shukla, Abhilasha; Gupta, Prashant; Rehan, Ahmad Danish; George, Jiji

2015-01-01

Candidiasis is the most common opportunistic infection in human immunodeficiency virus (HIV) seropositive patients, starting from asymptomatic colonization to pathogenic forms and gradual colonization of non-albicans in patients with advanced immunosuppression leads to resistance for azole group of antifungal drugs with high rate of morbidity and mortality. To isolate the Candida species and determine of antifungal drug susceptibility against fluconazole, itraconazole, nystatin, amphotericin B, and clotrimazolein HIV seropositive and control individuals, with or without clinical oropharyngeal candidiasis (OPC). Includes samples from faucial region of 70 subjects with and without clinical candidiasis in HIV seropositive and controls were aseptically inoculated onto Sabaraud's Dextrose Agar media and yeasts were identified for the specific species by Corn Meal Agar, sugar fermentation and heat tolerance tests. Antifungal drug susceptibility of the isolated species was done against above-mentioned drugs by E-test and disc diffusion method. The commonly isolated species in HIV seropositive and controls were Candida albicans, Candida glabrata and Candida tropicalis Candida guilliermondii and Candida dubliniensis isolated only in HIV seropositive patients. Susceptibility against selected antifungal drugs was observed more in HIV-negative individuals whereas susceptible dose-dependent and resistance were predominant in HIV-positive patients. Resistance is the major problem in the therapy of OPC, especially in HIV seropositive patients due to aggressive and prolonged use of antifungal agents, therefore, our study emphasizes the need for antifungal drug susceptibility testing whenever antifungal treatment is desired, especially in HIV-infected subjects.

Antifungal response of oral-associated candidal reference strains (American Type Culture Collection) by supercritical fluid extract of nutmeg seeds for geriatric denture wearers: An in vitro screening study.

PubMed

Iyer, Meenakshi; Gujjari, Anil Kumar; Gowda, Vishakante; Angadi, Shridhar

2017-01-01

Since time immemorial, plants have continued to play a predominant role in the maintenance of human health as sources of medicinal compounds. Several effective antifungal agents are available for oral Candida infections; the failure is not uncommon because isolates of Candida albicans may exhibit resistance to the drug during therapy. The present study aimed to identify an alternative, inexpensive, simple, and effective method of preventing and controlling the candidal infection. All the procured and authenticated nutmeg seeds were dried in shade and cleaned by hand sorting. The crushed seeds were passed through mesh no. 40 individually. About 50 g of powdered nutmeg seeds was loaded in the supercritical fluid extractor unit using supercritical CO 2 as extracting solvent in accordance with the methods of Nguyen et al . Supercritical fluid (SFE) extraction was done using CO 2 gas without any cosolvents. The nutmeg extract displayed antifungal activity with the effective zone of inhibition ranging from 18.0 to 12.0 mm when compared with nystatin as positive control. This paper described the in vitro antibacterial activity, and phytochemical analysis of SFE extract of nutmeg ( Myristica fragrans ) evaluated against C. albicans (American Type Culture Collection 10231) through agar well diffusion method. SFE of nutmeg seeds can be used as an adjunct to conventional therapy for oral candidiasis.

[Cutaneous Malassezia infections and Malassezia associated dermatoses: An update].

PubMed

Nenoff, P; Krüger, C; Mayser, P

2015-06-01

The lipophilic yeast fungus Malassezia (M.) spp. is the only fungal genus or species which is part of the physiological human microbiome. Today, at least 14 different Malassezia species are known; most of them can only be identified using molecular biological techniques. As a facultative pathogenic microorganism, Malassezia represents the causative agent both of superficial cutaneous infections and of blood stream infections. Pityriasis versicolor is the probably most frequent infection caused by Malassezia. Less common, Malassezia folliculitis occurs. There is only an episodic report on Malassezia-induced onychomycosis. Seborrhoeic dermatitis represents a Malassezia-associated inflammatory dermatosis. In addition, Malassezia allergenes should be considered as the trigger of "Head-Neck"-type atopic dermatitis. Ketoconazole possesses the strongest in vitro activity against Malassezia, and represents the treatment of choice for topical therapy of pityriasis versicolor. Alternatives include other azole antifungals but also the allylamine terbinafine and the hydroxypyridone antifungal agent ciclopirox olamine. "Antiseborrhoeic" agents, e.g. zinc pyrithione, selenium disulfide, and salicylic acid, are also effective in pityriasis versicolor. The drug of choice for oral treatment of pityriasis versicolor is itraconazole; an effective alternative represents fluconazole. Seborrhoeic dermatitis is best treated with topical medication, including topical corticosteroids and antifungal agents like ketoconazole or sertaconazole. Calcineurin inhibitors, e.g. pimecrolimus and tacrolimus, are reliable in seborrhoeic dermatitis, however are used off-label.

Antifungal, phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum acutidens and its three components, carvacrol, thymol and p-cymene.

PubMed

Kordali, Saban; Cakir, Ahmet; Ozer, Hakan; Cakmakci, Ramazan; Kesdek, Memis; Mete, Ebru

2008-12-01

The chemical composition of essential oil isolated by hydrodistillation from the aerial parts of Origanum acutidens was analyzed by GC-MS. Carvacrol (87.0%), p-cymene (2.0%), linalool acetate (1.7%), borneol (1.6%) and beta-caryophyllene (1.3%) were found to be as main constituents. Antifungal, phytotoxic and insecticidal activities of the oil and its aromatic monoterpene constituents, carvacrol, p-cymene and thymol were also determined. The antifungal assays showed that O. acutidens oil, carvacrol and thymol completely inhibited mycelial growth of 17 phytopathogenic fungi and their antifungal effects were higher than commercial fungicide, benomyl. However, p-cymene possessed lower antifungal activity. The oil, carvacrol and thymol completely inhibited the seed germination and seedling growth of Amaranthus retroflexus, Chenopodium album and Rumex crispus and also showed a potent phytotoxic effect against these plants. However, p-cymene did not show any phytotoxic effect. Furthermore, O. acutidens oil showed 68.3% and 36.7% mortality against Sitophilus granarius and Tribolium confusum adults, respectively. The findings of the present study suggest that antifungal and herbicidal properties of the oil can be attributed to its major component, carvacrol, and these agents have a potential to be used as fungicide, herbicide as well as insecticide.

Antifungal activity of secondary plant metabolites from potatoes (Solanum tuberosum L.): Glycoalkaloids and phenolic acids show synergistic effects.

PubMed

Sánchez-Maldonado, A F; Schieber, A; Gänzle, M G

2016-04-01

To study the antifungal effects of the potato secondary metabolites α-solanine, α-chaconine, solanidine and caffeic acid, alone or combined. Resistance to glycoalkaloids varied among the fungal species tested, as derived from minimum inhibitory concentrations assays. Synergistic antifungal activity between glycoalkaloids and phenolic compounds was found. Changes in the fluidity of fungal membranes caused by potato secondary plant metabolites were determined by calculation of the generalized polarization values. The results partially explained the synergistic effect between caffeic acid and α-chaconine and supported findings on membrane disruption mechanisms from previous studies on artificial membranes. LC/MS analysis was used to determine variability and relative amounts of sterols in the different fungal species. Results suggested that the sterol pattern of fungi is related to their resistance to potato glycoalkaloids and to their taxonomy. Fungal resistance to α-chaconine and possibly other glycoalkaloids is species dependent. α-Chaconine and caffeic acid show synergistic antifungal activity. The taxonomic classification and the sterol pattern play a role in fungal resistance to glycoalkaloids. Results improve the understanding of the antifungal mode of action of potato secondary metabolites, which is essential for their potential utilization as antifungal agents in nonfood systems. © 2016 The Society for Applied Microbiology.

Antifungal Effect of a Dental Tissue Conditioner Containing Nystatin-Loaded Alginate Microparticles.

PubMed

Kim, Hyun-Jin; Son, Jun Sik; Kwon, Tae-Yub

2018-02-01

In this in vitro study, nystatin-alginate microparticles were successfully fabricated to control the release of nystatin from a commercial dental tissue conditioner. These nystatin-alginate microparticles were spherical and had a slightly rough surface. The microparticles incorporated into the tissue conditioner were distributed homogeneously throughout the tissue conditioner matrix. The incorporation of the microparticles did not deteriorate the mechanical properties of the original material. The agar diffusion test results showed that the tissue conditioner containing the microparticles had a good antifungal effect against Candida albicans. The nystatin-alginate microparticles efficiently controlled the release of nystatin from the tissue conditioner matrix over the experimental period of 14 days. Moreover, the nystatin-alginate microparticles incorporated in the tissue conditioner showed effective antifungal function even at lower concentrations of nystatin. The current study suggests that the tissue conditioner containing the nystatin-alginate microparticle carrier system has potential as an effective antifungal material.

In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.

PubMed

Zeng, Hong; Chen, Xinping; Liang, Jingnan

2015-01-01

Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent. © 2015 The Authors.

KB425796-A, a novel antifungal antibiotic produced by Paenibacillus sp. 530603.

PubMed

Kai, Hirohito; Yamashita, Midori; Takase, Shigehiro; Hashimoto, Michizane; Muramatsu, Hideyuki; Nakamura, Ikuko; Yoshikawa, Koji; Ezaki, Masami; Nitta, Kumiko; Watanabe, Masato; Inamura, Noriaki; Fujie, Akihiko

2013-08-01

The novel antifungal macrocyclic lipopeptidolactone, KB425796-A (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new Paenibacillus species based on morphological and physiological characteristics, and 16S rRNA sequences. KB425796-A (1) was isolated as white powder by solvent extraction, HP-20 and ODS-B column chromatography, and lyophilization, and was determined to have the molecular formula C79H115N19O18. KB425796-A (1) showed antifungal activities against Aspergillus fumigatus and the micafungin-resistant infectious fungi Trichosporon asahii, Rhizopus oryzae, Pseudallescheria boydii and Cryptococcus neoformans.

Isolating antifungals from fungus-growing ant symbionts using a genome-guided chemistry approach.

PubMed

Seipke, Ryan F; Grüschow, Sabine; Goss, Rebecca J M; Hutchings, Matthew I

2012-01-01

We describe methods used to isolate and identify antifungal compounds from actinomycete strains associated with the leaf-cutter ant Acromyrmex octospinosus. These ants use antibiotics produced by symbiotic actinomycete bacteria to protect themselves and their fungal cultivar against bacterial and fungal infections. The fungal cultivar serves as the sole food source for the ant colony, which can number up to tens of thousands of individuals. We describe how we isolate bacteria from leaf-cutter ants collected in Trinidad and analyze the antifungal compounds made by two of these strains (Pseudonocardia and Streptomyces spp.), using a combination of genome analysis, mutagenesis, and chemical isolation. These methods should be generalizable to a wide variety of insect-symbiont situations. Although more time consuming than traditional activity-guided fractionation methods, this approach provides a powerful technique for unlocking the complete biosynthetic potential of individual strains and for avoiding the problems of rediscovery of known compounds. We describe the discovery of a novel nystatin compound, named nystatin P1, and identification of the biosynthetic pathway for antimycins, compounds that were first described more than 60 years ago. We also report that disruption of two known antifungal pathways in a single Streptomyces strain has revealed a third, and likely novel, antifungal plus four more pathways with unknown products. This validates our approach, which clearly has the potential to identify numerous new compounds, even from well-characterized actinomycete strains. Copyright © 2012 Elsevier Inc. All rights reserved.

Free radical scavenging capacity, anticandicidal effect of bioactive compounds from Sida cordifolia L., in combination with nystatin and clotrimazole and their effect on specific immune response in rats.

PubMed

Ouédraogo, Maurice; Konaté, Kiessoun; Lepengué, Alexis Nicaise; Souza, Alain; M'Batchi, Bertrand; Sawadogo, Laya L

2012-12-26

Infectious diseases caused by fungi are still a major threat to public health, despite numerous efforts by researchers. Use of ethnopharmacological knowledge is one attractive way to reduce empiricism and enhance the probability of success in new drug-finding efforts. In this work, the total alkaloid compounds (AC) from Sida cordifolia L. (Malvaceae) have been investigated for their free radical scavenging capacity, antifungal and immunostimulatory properties. The antifungal activity was investigated against five candida strains using the microplate dilution method and the Fractional Inhibitory Concentration Index (FICI) of compounds was evaluated. The antioxidant activity of the samples was evaluate using three separate methods, at last, the immunostimulatory effect on immunosuppressed wistar rats was performed. As for the antifungal activity, result varied according to microorganism. The results obtained in this antifungal activity were interesting and indicated a synergistic effect between alkaloid compounds and the antifungal references such as Nystatin and Clotrimazole. Antioxidant capacity noticed that the reduction capacity of DPPH radicals obtained the best result comparatively to the others methods of free radical scavenging. Our results showed a low immunostimulatory effect and this result could be explained by the lack of biologically active antioxidants such as polyphenol compounds lowly contained in the alkaloid compounds. The results of this study showed that alkaloid compounds in combination with antifungal references (Nystatin and Clotrimazole) exhibited antimicrobial effects against candida strains tested. The results supported the utilization of these plants in infectious diseases particularly in treatment of candida infections.

Free radical scavenging capacity, anticandicidal effect of bioactive compounds from Sida Cordifolia L., in combination with nystatin and clotrimazole and their effect on specific immune response in rats

PubMed Central

2012-01-01

Background Infectious diseases caused by fungi are still a major threat to public health, despite numerous efforts by researchers. Use of ethnopharmacological knowledge is one attractive way to reduce empiricism and enhance the probability of success in new drug-finding efforts. In this work, the total alkaloid compounds (AC) from Sida cordifolia L. (Malvaceae) have been investigated for their free radical scavenging capacity, antifungal and immunostimulatory properties. Method The antifungal activity was investigated against five candida strains using the microplate dilution method and the Fractional Inhibitory Concentration Index (FICI) of compounds was evaluated. The antioxidant activity of the samples was evaluate using three separate methods, at last, the immunostimulatory effect on immunosuppressed wistar rats was performed. Results As for the antifungal activity, result varied according to microorganism. The results obtained in this antifungal activity were interesting and indicated a synergistic effect between alkaloid compounds and the antifungal references such as Nystatin and Clotrimazole. Antioxidant capacity noticed that the reduction capacity of DPPH radicals obtained the best result comparatively to the others methods of free radical scavenging. Our results showed a low immunostimulatory effect and this result could be explained by the lack of biologically active antioxidants such as polyphenol compounds lowly contained in the alkaloid compounds. Conclusion The results of this study showed that alkaloid compounds in combination with antifungal references (Nystatin and Clotrimazole) exhibited antimicrobial effects against candida strains tested. The results supported the utilization of these plants in infectious diseases particularly in treatment of candida infections. PMID:23268761

Antifungal Activity of Lactic Acid Bacteria Strains Isolated from Natural Honey against Pathogenic Candida Species

PubMed Central

Bulgasem, Bulgasem Y.; Lani, Mohd Nizam; Wan Yusoff, Wan Mohtar; Fnaish, Sumaya G.

2016-01-01

The role of lactic acid bacteria (LAB) in honey as antifungal activity has received little attention and their mechanism of inhibitory of fungi is not fully understood. In this study, LAB were isolated from honey samples from Malaysia, Libya, Saudi Arabia, and Yemen. Twenty-five isolates were confirmed LAB by catalase test and Gram staining, and were screened for antifungal activity. Four LAB showed inhibitory activity against Candida spp. using the dual agar overlay method. And they were identified as Lactobacillus plantarum HS isolated from Al-Seder honey, Lactobacillus curvatus HH isolated from Al-Hanon honey, Pediococcus acidilactici HC isolated from Tualang honey and Pediococcus pentosaceus HM isolated from Al-Maray honey by the 16S rDNA sequence. The growth of Candida glabrata ATCC 2001 was strongly inhibited (>15.0 mm) and (10~15 mm) by the isolates of L. curvatus HH and P. pentosaceus HM, respectively. The antifungal activity of the crude supernatant (cell free supernatant, CFS) was evaluated using well diffusion method. The CFS showed high antifungal activity against Candida spp. especially The CFS of L. curvatus HH was significantly (p < 0.05) inhibited growth of C. glabrata ATCC 2001, C. parapsilosis ATCC 2201, and C. tropicalis ATCC 750 with inhibitory zone 22.0, 15.6, and 14.7 mm, respectively. While CFS of P. pentosaceus HM was significantly (p < 0.05) effective against C. krusei, C. glabrata, and C. albicans with inhibition zone 17.2, 16.0, and 13.3 mm, respectively. The results indicated that LAB isolated from honey produced compounds which can be used to inhibit the growth of the pathogenic Candida species. PMID:28154488

Antifungal Activity of Lactic Acid Bacteria Strains Isolated from Natural Honey against Pathogenic Candida Species.

PubMed

Bulgasem, Bulgasem Y; Lani, Mohd Nizam; Hassan, Zaiton; Wan Yusoff, Wan Mohtar; Fnaish, Sumaya G

2016-12-01

The role of lactic acid bacteria (LAB) in honey as antifungal activity has received little attention and their mechanism of inhibitory of fungi is not fully understood. In this study, LAB were isolated from honey samples from Malaysia, Libya, Saudi Arabia, and Yemen. Twenty-five isolates were confirmed LAB by catalase test and Gram staining, and were screened for antifungal activity. Four LAB showed inhibitory activity against Candida spp. using the dual agar overlay method. And they were identified as Lactobacillus plantarum HS isolated from Al-Seder honey, Lactobacillus curvatus HH isolated from Al-Hanon honey, Pediococcus acidilactici HC isolated from Tualang honey and Pediococcus pentosaceus HM isolated from Al-Maray honey by the 16S rDNA sequence. The growth of Candida glabrata ATCC 2001 was strongly inhibited (>15.0 mm) and (10~15 mm) by the isolates of L. curvatus HH and P. pentosaceus HM, respectively. The antifungal activity of the crude supernatant (cell free supernatant, CFS) was evaluated using well diffusion method. The CFS showed high antifungal activity against Candida spp. especially The CFS of L. curvatus HH was significantly ( p < 0.05) inhibited growth of C. glabrata ATCC 2001, C. parapsilosis ATCC 2201, and C. tropicalis ATCC 750 with inhibitory zone 22.0, 15.6, and 14.7 mm, respectively. While CFS of P. pentosaceus HM was significantly ( p < 0.05) effective against C. krusei , C. glabrata , and C. albicans with inhibition zone 17.2, 16.0, and 13.3 mm, respectively. The results indicated that LAB isolated from honey produced compounds which can be used to inhibit the growth of the pathogenic Candida species.

Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical Candida Isolates

PubMed Central

Kuipers, M. E.; de Vries, H. G.; Eikelboom, M. C.; Meijer, D. K. F.; Swart, P. J.

1999-01-01

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg · ml−1. Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated. PMID:10543740

Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates.

PubMed

Kuipers, M E; de Vries, H G; Eikelboom, M C; Meijer, D K; Swart, P J

1999-11-01

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg. ml(-1). Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.

Antifungal modes of action of Saccharomyces and other biocontrol yeasts against fungi isolated from sour and grey rots.

PubMed

Nally, M C; Pesce, V M; Maturano, Y P; Rodriguez Assaf, L A; Toro, M E; Castellanos de Figueroa, L I; Vazquez, F

2015-07-02

The aim of this study was to determine the putative modes of action of 59 viticultural yeasts (31 Saccharomyces and 28 non-Saccharomyces) that inhibited fungi isolated from sour and grey rot in grapes. Inhibition of fungal mycelial growth by metabolites, enzyme activities (laminarinases, chitinases), antifungal volatiles, competition for nutrients (siderophores, Niche Overlap Index (NOI)), inhibition of fungal spore germination and decreased germinal tube length and induction of resistance were assayed. Biofungicide yeasts were classified into "antifungal patterns", according to their mechanisms of action. Thirty isolates presented at least two of the mechanisms assayed. We propose that inhibition of fungal mycelial growth by metabolites, laminarinases, competition for nutrients, inhibition of fungal spore germination and decreased germinal tube length, and antifungal volatiles by Saccharomyces and non-Saccharomyces viticultural yeasts is used as putative biocontrol mechanisms against phytopathogenic fungi. Twenty-four different antifungal patterns were identified. Siderophore production (N)and a combination of siderophore production and NOI>0.92 (M)were the most frequent antifungal patterns observed in the biofungicide yeasts assayed. Elucidation of these mechanisms could be useful for optimization of an inoculum formulation, resulting in a more consistent control of grey and sour rot with Saccharomyces and non-Saccharomyces biocontrol yeasts. Copyright © 2015 Elsevier B.V. All rights reserved.

A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients. Gruppo Italiano Malattie Ematologiche dell'Adulto, Gruppo Italiano Trapianto di Midollo Osseo, Associazione Italiana Ematologia ed Oncologia Pediatrica, Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Sorveglianza Epidemiologica delle Infezioni Fungine nelle Emopatie Maligne.

PubMed

Girmenia, Corrado; Aversa, Franco; Busca, Alessandro; Candoni, Anna; Cesaro, Simone; Luppi, Mario; Pagano, Livio; Rossi, Giuseppe; Venditti, Adriano; Nosari, Anna Maria

2013-09-01

In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up. Copyright © 2012 John Wiley & Sons, Ltd.

[Evaluation of PNA-FISH method for direct identification of Candida species in blood culture samples and its potential impact on guidance of antifungal therapy].

PubMed

Doğan, Özlem; İnkaya, Ahmet Çağkan; Gülmez, Dolunay; Uzun, Ömrüm; Akova, Murat; Arıkan Akdağlı, Sevtap

2016-10-01

Early antifungal therapy has a major influence on survival in candidemia. Rapid identification of the species has importance for the treatment, prediction of the species-specific primary resistance and variable antifungal susceptibility. Recently, molecular-based methods attempt to reduce the time between the positive signal of a blood culture and identification of the fungus. PNA-FISH (Peptide nucleic acid fluorescence in situ hybridization) assay distinguishes a number of frequently isolated Candida species in groups following the growth in blood culture. The aim of this study was to investigate the correlation of the species identified by PNA-FISH with conventional identification methods in yeast positive blood cultures and its influence on the selection of antifungal therapy. Specimens of adult patients diagnosed as yeast with Gram stain in signal-positive blood cultures between August to December 2013, were included in the study. The strains were concomitantly cultivated by subculturing from the blood culture bottles onto solid media and identified by conventional methods (germ tube test, ID32C and morphology on cornmeal Tween 80 agar). Rapid species identification was performed by Yeast Traffic Light PNA-FISH, which generates green flourescence for Candida albicans and Candida parapsilosis, yellow for Candida tropicalis, and red for Candida krusei and Candida glabrata. C.tropicalis was identified as a single species whereas the others were identified in pairs. The time points when the yeast positive blood culture bottle was received by the mycology laboratory and reporting of the species identification results by PNA-FISH and the conventional methods were recorded. Seven C.albicans, six C.glabrata, three C.parapsilosis, one C.tropicalis, one C.krusei, one Cryptococcus neoformans, one Saprochaete capitata (Blastoschizomyces capitatus), one C.albicans and Candida dubliniensis, one C.krusei and C.dubliniensis, and one C.glabrata and C.parapsilosis were identified by conventional methods in 23 specimens. Results of PNA-FISH and conventional methods were in full agreement in 19 of the 23 specimens (82.6%). Two specimens were negative by PNA-FISH and yielded S.capitata and C.neoformans which were not included in the test panel. In three specimens that were infected with multiple species, PNA-FISH detected only one of the species. On the other hand and in one specimen, PNA-FISH detected a second species (C.glabrata or C.krusei) that could not be isolated and identified conventionally. Species identification were obtained 72 hours (mean) earlier with PNA-FISH. PNA-FISH provided accurate species identification that were consistent with conventional methods. However and expectedly, it failed to detect species that were not included in the test panel. During the study period, 13 of the 23 patients have passed away. Apart from six patients died prior to blood culture positivity and the one that could not get any antifungal therapy during hospital stay, 16 patients received antifungal treatment. Of sixteen patients who received antifungal therapy, initial antifungal treatment was fluconazole for five and echinocandin for 10 patients. Fluconazole and amphotericin B combination was preferred for one patient. In this study, PNA-FISH result had an influence on the modification of the antifungal treatment of only for one patient in accordance with the clinical findings. We conclude that the utility of PNA-FISH method appeared to be limited in our center since the assay cannot differentiate C.albicans and C.parapsilosis, the two commonly isolated species among our candidemia isolates. However, advantages of the assay might be more pronounced for the centers where C.glabrata is a relatively more frequent species.

Synthesis and antifungal activity of natural product-based 6-alkyl-2 3 4 5-tetrahydropyridines

USDA-ARS?s Scientific Manuscript database

Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural products piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexa...

Lactic acid bacteria with potential to eliminate fungal spoilage in foods.

PubMed

Rouse, S; Harnett, D; Vaughan, A; van Sinderen, D

2008-03-01

To investigate antifungal activity produced by lactic acid bacteria (LAB) isolated from malted cereals and to determine if such LAB have the capacity to prevent fungal growth in a particular food model system. The effect of pH, temperature and carbon source on production of antifungal activity by four LAB was determined. Pediococcus pentosaceus was used to conduct a trial to determine if it is feasible to eliminate Penicillium expansum, the mould responsible for apple rot, using an apple model. Penicillium expansum was incapable of growth during the trial on apple-based agar plates inoculated with the antifungal-producing culture, whereas the mould did grow on apple plates inoculated with an LAB possessing no antifungal activity. Partial characterization of the antifungal compounds indicates that their activity is likely to be because of production of antifungal peptides. The trial conducted showed that the antifungal culture has the ability to prevent growth of the mould involved in apple spoilage, using apples as a model. The ability of an LAB to prevent growth of Pen. expansum using the apple model suggests that these antifungal LAB have potential applications in the food industry to prevent fungal spoilage of food.

In Vitro Activities of 35 Double Combinations of Antifungal Agents against Scedosporium apiospermum and Scedosporium prolificans▿

PubMed Central

Cuenca-Estrella, Manuel; Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Bernal-Martinez, Leticia; Gomez-Lopez, Alicia; Buitrago, Maria J.; Mellado, Emilia; Rodriguez-Tudela, Juan L.

2008-01-01

Activities of 35 combinations of antifungal agents against Scedosporium spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against Scedosporium apiospermum. Antagonism was absent for all antifungal combinations against both species. PMID:18195067

In vitro antifungal activity of antipsychotic drugs and their combinations with conventional antifungals against Scedosporium and Pseudallescheria isolates.

PubMed

Homa, Mónika; Galgóczy, László; Tóth, Eszter; Tóth, Liliána; Papp, Tamás; Chandrasekaran, Muthusamy; Kadaikunnan, Shine; Alharbi, Naiyf S; Vágvölgyi, Csaba

2015-11-01

In the present study, in vitro antifungal activities of five antipsychotic drugs (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ; amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB; caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were investigated in broth microdilution tests against four clinical and five environmental Scedosporium and Pseudallescheria isolates. When used alone, phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in vitro combinations with AMB, CSP, VRC, and TRB were also examined against the clinical isolates. In combination with antifungal agents, CPZ was able to act synergistically with AMB and TRB in cases of one and two isolates, respectively. In all other cases, indifferent interactions were revealed. Antagonism was not observed between the tested agents. These combinations may establish a more effective and less toxic therapy after further in vitro and in vivo studies for Scedosporium and Pseudallescheria infections. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antifungal activity of low molecular weight chitosan against clinical isolates of Candida spp.

PubMed

Alburquenque, Claudio; Bucarey, Sergio A; Neira-Carrillo, Andrónico; Urzúa, Blanca; Hermosilla, Germán; Tapia, Cecilia V

2010-12-01

Chitosan is a natural polymer derived from chitin, a structural component of fungi, insects and shrimp, which exerts antimicrobial effects against bacteria and fungi. The aim of this study was to investigate the in vitro antifungal activity of low molecular weight chitosan (LMWC), and the potential synergy between chitosan and a currently used antifungal drug, fluconazole. The in vitro minimal inhibitory concentrations (MICs) of chitosan and fluconazole against 105 clinical Candida isolates were measured by the broth microdilution method. LMWC exhibited a significant antifungal activity, inhibiting over 89.9% of the clinical isolates examined (68.6% of which was completely inhibited). The species included several fluconazole-resistant strains and less susceptible species such as C. glabrata, which was inhibited at a concentration of 4.8 mg/l LMWC. Although some strains were susceptible at pH 7.0, a greater antifungal activity of LMWC was observed at pH 4.0. There was no evidence of a synergistic effect of the combination of LMWC and fluconazole at pH 7.0. This is the first report in which the antifungal activity of LMWC was investigated with clinical Candida strains. The use of LMWC as an antifungal compound opens new therapeutic perspectives, as the low toxicity of LMWC in humans supports its use in new applications in an environment of pH 4.0-4.5, such as a topical agent for vulvovaginal candidiasis.

In vitro antifungal activity and probable fungicidal mechanism of aqueous extract of Barleria grandiflora.

PubMed

Kumari, Suman; Jain, Preeti; Sharma, Bhawana; Kadyan, Preeti; Dabur, Rajesh

2015-04-01

Barleria grandiflora Dalz. (Acanthaceae) is being used in India to treat different types of disorders including skin infections. Therefore, there are good possibilities to find antifungal compounds in its extracts with novel mechanism of action. The main objectives of the present study were to evaluate the antifungal activity of plant extracts and to study its effects on metabolic pathways of A. fumigatus. The microbroth dilution assay was used to explore antifungal activity and MIC of various extracts. Metabolic profiles of control and treated cultures were collected from Q-TOF-MS interfaced with HPLC. Affected metabolic pathways of A. fumigatus after the treatment were analyzed by discrimination analysis of mass data. Antifungal activities were observed in hot and cold water extracts of the plant. Hot water extract of B. grandiflora showed significant activity against tested fungi in the range 0.625-1.25 mg/mL. Partial least discrimination analysis revealed that the hot water plant extract downregulated amino acid, glyoxylate pathway, and methylcitrate pathways at the same time due to the synergistic effects of secondary metabolites. Hot water extract also downregulated several other metabolic pathways unique to fungi indicating its specific activity toward fungi. B. grandiflora showed promising antifungal activity which can further be exploited by identification of active compounds, to inhibit the specific fungal pathways and development of novel therapeutic antifungal drugs.

Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study.

PubMed

de Castro, Ricardo Dias; de Souza, Trícia Murielly Pereira Andrade; Bezerra, Louise Morais Dornelas; Ferreira, Gabriela Lacet Silva; Costa, Edja Maria Melo de Brito; Cavalcanti, Alessandro Leite

2015-11-24

Limitations of antifungal agents used in the treatment of oral candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to evaluate the antifungal activity of thymol against Candida albicans, Candida tropicalis and Candida krusei strains and to determine its mode of action and synergistic effect when combined with the synthetic antifungal nystatin. The minimum inhibitory concentration (MIC) was determined using a microdilution technique, and the minimum fungicidal concentration (MFC) was determined via subculture sowing. The mode of action of thymol was established by verifying fungal growth in the presence of sorbitol or ergosterol. The fractional inhibitory concentration index (FIC) was determined using the checkerboard method. Thymol presented an antifungal effect, with MICs of 39 μg/mL for C. albicans and C. krusei and 78 μg/mL for C. tropicalis. The results of the antifungal test remained unchanged in the presence of sorbitol; however, the MIC value of thymol against C. albicans increased eight times (from 39.0 to 312.5 μg/mL) in presence of exogenous ergosterol. The combination of thymol and nystatin reduced the MIC values of both products by 87.4%, generating an FIC index of 0.25. Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with nystatin.

Biofilm-forming capacity of blood-borne Candida albicans strains and effects of antifungal agents.

PubMed

Turan, Hanni; Demirbilek, Müge

Infections related to Candida albicans biofilms and subsequent antifungal resistance have become more common with the increased use of indwelling medical devices. Regimens for preventing fungal biofilm formation are needed, particularly in high-risk patients. In this study, we investigated the biofilm formation rate of multiple strains of Candida albicans (n=162 clinical isolates), their antifungal susceptibility patterns, and the efficacy of certain antifungals for preventing biofilm formation. Biofilm formation was graded using a modified Christensen's 96-well plate method. We further analyzed 30 randomly chosen intense biofilm-forming isolates using the XTT method. Minimum biofilm inhibition concentrations (MBIC) of caspofungin, micafungin, anidulafungin, fluconazole, voriconazole, posaconazole, itraconazole, and amphotericin B were determined using the modified Calgary biofilm method. In addition, the inhibitory effects of antifungal agents on biofilm formation were investigated. Our study showed weak, moderate, and extensive biofilm formation in 29% (n=47), 38% (n=61), and 23% (n=37) of the isolates, respectively. We found that echinocandins had the lowest MBIC values and that itraconazole inhibited biofilm formation in more isolates (26/32; 81.3%) than other tested agents. In conclusion, echinocandins were most effective against formed biofilms, while itraconazole was most effective for preventing biofilm formation. Standardized methods are needed for biofilm antifungal sensitivity tests when determining the treatment and prophylaxis of C. albicans infections. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Training should be the first step toward an antifungal stewardship program.

PubMed

Valerio, Maricela; Muñoz, Patricia; Rodríguez-González, Carmen; Sanjurjo, María; Guinea, Jesús; Bouza, Emilio

2015-04-01

The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Biogenic Silver Nanoparticles by Gelidiella acerosa Extract and their Antifungal Effects

PubMed Central

Vivek, Marimuthu; Kumar, Palanisamy Senthil; Steffi, Sesurajan; Sudha, Sellappa

2011-01-01

The synthesis, characterization and application of biologically synthesized nanomaterials are an important aspect in nanotechnology. The present study deals with the synthesis of silver nanoparticles (Ag-NPs) using the aqueous extract of red seaweed Gelidiella acerosa as the reducing agent to study the antifungal activity. The formation of Ag-NPs was confirmed by UV-Visible Spectroscopy, X-Ray Diffraction (XRD) pattern, Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The synthesized Ag-NPs was predominately spherical in shape and polydispersed. Fourier Transform Infra-Red (FT-IR) spectroscopy analysis showed that the synthesized nano-Ag was capped with bimolecular compounds which are responsible for reduction of silver ions. The antifungal effects of these nanoparticles were studied against Humicola insolens (MTCC 4520), Fusarium dimerum (MTCC 6583), Mucor indicus (MTCC 3318) and Trichoderma reesei (MTCC 3929). The present study indicates that Ag-NPs have considerable antifungal activity in comparison with standard antifungal drug, and hence further investigation for clinical applications is necessary. PMID:23408653

Syntheses of new rare earth complexes with carboxymethylated polysaccharides and evaluation of their in vitro antifungal activities.

PubMed

Sun, Xiaobo; Jin, Xiaozhe; Pan, Wei; Wang, Jinping

2014-11-26

In the present paper, La, Eu and Yb were selected to represent light, middle and heavy rare earths to form complexes with polysaccharides through chelating coordination of carboxyl groups, which were added into polysaccharide chains by means of carboxymethylation. Their antifungal activities against plant pathogenic fungi were evaluated using growth rate method. These rare earth complexes exhibited various antifungal activities against the tested fungi, depending on rare earth elements, polysaccharide types and fungal species. Among these three metal elements (i.e. La, Eu and Yb), Yb formed the complexes with the most effective antifungal properties. Furthermore, the results showed that ligands of carboxymethylated polysaccharides played a key role in promoting cytotoxicity of the rare earth complexes. Carboxymethylated Ganoderma applanatum polysaccharide (CGAP) was found to be the most effective ligand to form complexes with antifungal activities, followed by carboxymethylated lentinan (CLNT) and carboxymethylated Momordica charantia polysaccharide (CMCP). Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus.

PubMed

Hu, Yichen; Zhang, Jinming; Kong, Weijun; Zhao, Gang; Yang, Meihua

2017-04-01

The antifungal activity and potential mechanisms in vitro as well as anti-aflatoxigenic efficiency in vivo of natural essential oil (EO) derived from turmeric (Curcuma longa L.) against Aspergillus flavus was intensively investigated. Based on the previous chemical characterization of turmeric EO by gas chromatography-mass spectrometry, the substantially antifungal activities of turmeric EO on the mycelial growth, spore germination and aflatoxin production were observed in a dose-dependent manner. Furthermore, these antifungal effects were related to the disruption of fungal cell endomembrane system including the plasma membrane and mitochondria, specifically i.e. the inhibition of ergosterol synthesis, mitochondrial ATPase, malate dehydrogenase, and succinate dehydrogenase activities. Moreover, the down-regulation profiles of turmeric EO on the relative expression of mycotoxin genes in aflatoxin biosynthetic pathway revealed its anti-aflatoxigenic mechanism. Finally, the suppression effect of fungal contamination in maize indicated that turmeric EO has potential as an eco-friendly antifungal agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

PubMed Central

Liu, Xinning; Wang, Decai; Yu, Cuixiang; Li, Tao; Liu, Jianqiao; Sun, Shujuan

2016-01-01

Candida is an important opportunistic fungal pathogen, especially in biofilm associated infections. The formation of a Candida biofilm can decrease Candida sensitivity to antifungal drugs and cause drug resistance. Although many effective antifungal drugs are available, their applications are limited due to their high toxicity and cost. Seeking new antifungal agents that are effective against biofilm-associated infection is an urgent need. Many research efforts are underway, and some progress has been made in this field. It has been shown that the arachidonic acid cascade plays an important role in fungal morphogenesis and pathogenicity. Notably, prostaglandin E2 (PGE2) can promote the formation of a Candida biofilm. Recently, the inhibition of PGE2 has received much attention. Studies have shown that cyclooxygenase (COX) inhibitors, such as aspirin, ibuprofen, and indomethacin, combined with fluconazole can significantly reduce Candida adhesion and biofilm development and increase fluconazole susceptibility; the MIC of fluconazole can be decrease from 64 to 2 μg/ml when used in combination with ibuprofen. In addition, in vivo studies have also confirmed the antifungal activities of these inhibitors. In this article, we mainly review the relationship between PGE2 and Candida biofilm, summarize the antifungal activities of COX inhibitors and analyze the possible antifungal activity of microsomal prostaglandin E synthase-1 (MPGES-1) inhibitors; additionally, other factors that influence PGE2 production are also discussed. Hopefully this review can disclose potential antifungal targets based on the arachidonic acid cascade and provide a prevailing strategy to alleviate Candida albicans biofilm formation. PMID:27999568

Evaluation of antifungal activities of the essential oil and various extracts of Nigella sativa and its main component, thymoquinone against pathogenic dermatophyte strains.

PubMed

Mahmoudvand, H; Sepahvand, A; Jahanbakhsh, S; Ezatpour, B; Ayatollahi Mousavi, S A

2014-12-01

Plant extracts and plant-derived compounds are valuable sources as folk medicine for the treatment and prevention of a wide range of diseases including infectious diseases. In the present study, the antifungal activities of the essential oil and various extracts Nigella sativa and its active principle, thymoquinone against Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum as pathogenic dermatophyte strains have been evaluated. In addition, the cytotoxic effects of N. sativa against murine macrophage cells were determined. In this study, the antifungal activity was studied by disk diffusion method and assessment of minimum inhibitory concentration (MIC) of extracts using broth macrodilution method. In addition, the cytotoxic activity of N. sativa was evaluated by colorimetric assay (MTT). The components of the N. sativa essential oil were also identified by gas chromatography/mass spectroscopy (GC/MS) analysis. The results showed that the essential oil and various extracts of N. sativa particularly thymoquinone have potent antifungal effects on T. mentagrophytes, M. canis and M. gypseum as pathogenic dermatophyte strains. In the assessment of the cytotoxicity activity, it could be observed that N. sativa had no significant cytotoxicity in the murine macrophages at low concentrations. While, thymoquinone in comparison with essential oil and various extracts of N. sativa showed higher cytotoxicity on murine macrophage cells. In the GC/MS analysis, thymoquinone (42.4%), p-cymene (14.1%), carvacrol (10.3%) and longifolene (6.1%) were found to be the major components of N. sativa essential oil. The findings of this study suggest a first step in the search of new antidermatophytic drugs and aid the use of N. sativa seeds in the traditional medicine for dermatophytic infections. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Potato Dextrose Agar Antifungal Susceptibility Testing for Yeasts and Molds: Evaluation of Phosphate Effect on Antifungal Activity of CMT-3

PubMed Central

Liu, Yu; Tortora, George; Ryan, Maria E.; Lee, Hsi-Ming; Golub, Lorne M.

2002-01-01

The broth macrodilution method (BMM) for antifungal susceptibility testing, approved by the National Committee for Clinical Laboratory Standards (NCCLS), was found to have deficiencies in testing of the antifungal activity of a new type of antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3). The high content of phosphate in the medium was found to greatly increase the MICs of CMT-3. To avoid the interference of phosphate in the test, a new method using potato dextrose agar (PDA) as a culture medium was developed. Eight strains of fungi, including five American Type Culture Collection strains and three clinical isolates, were used to determine the MICs of amphotericin B and itraconazole with both the BMM and the PDA methods. The MICs of the two antifungal agents determined with the PDA method showed 99% agreement with those determined with the BMM method within 1 log2 dilution. Similarly, the overall reproducibility of the MICs with the PDA method was above 97%. Three other antifungal agents, fluconazole, ketoconazole, and CMT-3, were also tested in parallel against yeasts and molds with both the BMM and the PDA methods. The MICs of fluconazole and ketoconazole determined with the PDA method showed 100% agreement within 1 log2 dilution of those obtained with the BMM method. However, the MICs of CMT-3 determined with the BMM method were as high as 128 times those determined with the PDA method. The effect of phosphate on the antifungal activity of CMT-3 was evaluated by adding Na2HPO4 to PDA in the new method. It was found that the MIC of CMT-3 against a Penicillium sp. increased from 0.5 μg/ml (control) to 2.0 μg/ml when the added phosphate was used at a concentration of 0.8 mg/ml, indicating a strong interference of Na2HPO4 with the antifungal activity of CMT-3. Except for fluconazole, all the other antifungal agents demonstrated clear end points among the yeasts and molds tested. Nevertheless, with its high reproducibility, good agreement with NCCLS proposed MIC ranges, and lack of interference of phosphate, the PDA method shows promise as a useful assay for antifungal susceptibility testing and screening for new antifungal agents, especially for drugs that may be affected by high (supraphysiologic) phosphate concentrations. PMID:11959582

Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills.

PubMed

Fierascu, Irina; Ungureanu, Camelia; Avramescu, Sorin Marius; Cimpeanu, Carmen; Georgescu, Mihaela Ioana; Fierascu, Radu Claudiu; Ortan, Alina; Sutan, Anca Nicoleta; Anuta, Valentina; Zanfirescu, Anca; Dinu-Pirvu, Cristina Elena; Velescu, Bruno Stefan

2018-01-04

Juniperus communis L. represents a multi-purpose crop used in the pharmaceutical, food, and cosmetic industry. Several studies present the possible medicinal properties of different Juniperus taxa native to specific geographical area. The present study aims to evaluate the genoprotective, antioxidant, antifungal and anti-inflammatory potential of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills. The prepared hydroethanolic extract of Juniperus communis L. was characterized by GC-MS, HPLC, UV-Vis spectrometry and phytochemical assays. The antioxidant potential was evaluated using the DPPH assay, the antifungal effect was studied on Aspergillus niger ATCC 15475 and Penicillium hirsutum ATCC 52323, while the genoprotective effect was evaluated using the Allium cepa assay. The anti-inflammatory effect was evaluated in two inflammation experimental models (dextran and kaolin) by plethysmometry. Male Wistar rats were treated by gavage with distilled water (negative control), the microemulsion (positive control), diclofenac sodium aqueous solution (reference) and microemulsions containing juniper extract (experimental group). The initial paw volume and the paw volumes at 1, 2, 3, 4, 5 and 24 h were measured. Total terpenoids, phenolics and flavonoids were estimated to be 13.44 ± 0.14 mg linalool equivalent, 19.23 ± 1.32 mg gallic acid equivalent, and 5109.6 ± 21.47 mg rutin equivalent per 100 g of extract, respectively. GC-MS characterization of the juniper extract identified 57 volatile compounds in the sample, while the HPLC analysis revealed the presence of the selected compounds (α-pinene, chlorogenic acid, rutin, apigenin, quercitin). The antioxidant potential of the crude extract was found to be 81.63 ± 0.38% (measured by the DPPH method). The results of the antifungal activity assay (for Aspergillus niger and Penicillium hirsutum) were 21.6 mm, respectively 17.2 mm as inhibition zone. Test results demonstrated the genoprotective potential of J. communis undiluted extract, inhibiting the mitodepressive effect of ethanol. The anti-inflammatory action of the juniper extract, administered as microemulsion in acute-dextran model was increased when compared to kaolin subacute inflammation induced model. The hydroalcoholic extract obtained from wild-growing Juniperus communis native to Romanian southern sub-Carpathian hills has genoprotective, antioxidant, antifungal and anti-inflammatory properties.

Fungistatic activity of heat-treated flaxseed determined by response surface methodology.

PubMed

Xu, Y; Hall, C; Wolf-Hall, C

2008-08-01

The objective of this study was to evaluate the effect of heat treatment on the fungistatic activity of flaxseed (Linum usitatissimum) in potato dextrose agar (PDA) medium and a fresh noodle system. The radial growth of Penicilliumn chrysogenum, Aspergillus flavus, and a Penicillium sp. isolated from moldy noodles, as well as the mold count of fresh noodle enriched with heat treated flaxseed, were used to assess antifungal activity. A central composite design in the response surface methodology was used to predict the effect of heating temperature and time on antifungal activity of flaxseed flour (FF). Statistical analysis determined that the linear terms of both variables (that is, heating temperature and time) and the quadratic terms of the heating temperature had significant (P<0.05) effects on the radial growth of all 3 test fungi and the mold count log-cycle reduction of fresh noodle. The interactions between the temperature and time were significant for all dependent variables (P<0.05). Significant reductions in antifungal activities were found when FF was subjected to high temperatures, regardless of heating time. In contrast, prolonging the heating time did not substantially affect the antifungal activities of FF at low temperature. However, 60% of the antifungal activity was retained after FF was heated at 100 degrees C for 15 min, which suggests a potential use of FF as an antifungal additive in food products subjected to low to mild heat treatments.

Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.

PubMed

Tripathi, Himanshu; Luqman, Suaib; Meena, Abha; Khan, Feroz

2014-01-01

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.

Design, synthesis of novel chitosan derivatives bearing quaternary phosphonium salts and evaluation of antifungal activity.

PubMed

Tan, Wenqiang; Zhang, Jingjing; Luan, Fang; Wei, Lijie; Chen, Yuan; Dong, Fang; Li, Qing; Guo, Zhanyong

2017-09-01

Two novel chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized, including tricyclohexylphosphonium acetyl chitosan chloride (TCPACSC) and triphenylphosphonium acetyl chitosan chloride (TPPACSC), and characterized by FTIR, 1 H NMR, and 13 C NMR spectra. The degree of substitution was also calculated by elemental analysis results. Their antifungal activities against Colletotrichum lagenarium, Watermelon fusarium, and Fusarium oxysporum were investigated in vitro using the radial growth assay, minimal inhibitory concentration, and minimum bactericidal concentration assay. The fungicidal assessment revealed that the synthesized chitosan derivatives had superior antifungal activity compared with chitosan. Especially, TPPACSC exhibited the best antifungal property with inhibitory indices of over 75% at 1.0mg/mL. The results obviously showed that quaternary phosphonium groups could effectively enhance antifungal activity of the synthesized chitosan derivatives. Meanwhile, it was also found that their antifungal activity was influenced by electron-withdrawing ability of the quaternary phosphonium salts. The synthetic strategy described here could be utilized for the development of chitosan as antifungal biomaterials. Copyright © 2017 Elsevier B.V. All rights reserved.

Reveromycins A and B from Streptomyces sp. 3–10: Antifungal activity against plant pathogenic fungi in vitro and in a strawberry food model system

USDA-ARS?s Scientific Manuscript database

This study was conducted to determine the antifungal activity of the metabolites from Streptomyces sp. 3–10, and to purify and identify the metabolites. Meanwhile, the taxonomic status of strain 3–10 was re-evaluated. The cultural filtrates of strain 3–10 in potato dextrose broth were extract...

Antifungal Therapy for Systemic Mycosis and the Nanobiotechnology Era: Improving Efficacy, Biodistribution and Toxicity.

PubMed

Souza, Ana C O; Amaral, Andre C

2017-01-01

Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo . In this review, we provide a discussion about conventional antifungal and nanoantifungal therapies for systemic mycosis.

Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer.

PubMed

Proaño-Bolaños, Carolina; Zhou, Mei; Wang, Lei; Coloma, Luis A; Chen, Tianbao; Shaw, Chris

2016-09-02

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20-32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD- and the sequence motifs -VALGAVSK- or -GKAAL(N/G/S) (V/A)V- in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3-fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11μM). CZS-1 reached 100% haemolysis at 120.87μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use. Through the combination of molecular cloning, Edman degradation sequencing, tandem mass spectrometry and MALDI-TOF MS we have identified a new family of 15 antimicrobial peptides in the skin secretion of Cruziohyla calcarifer. The novel family is named "Cruzioseptins" and contains cationic amphipathic peptides of 20-32 residues. They have a broad range of antimicrobial activity that also includes effective antifungals with low haemolytic activity. Therefore, C. calcarifer has proven to be a rich source of novel peptides, which could become leading structures for the development of novel antibiotics and antifungals of clinical application. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro inhibitory effects of farnesol and interactions between farnesol and antifungals against biofilms of Candida albicans resistant strains.

PubMed

Xia, Jinping; Qian, Fang; Xu, Wenqian; Zhang, Zhenzhen; Wei, Xin

2017-04-01

Antifungal resistance is a serious problem in clinical infections. Farnesol, which is a potential antifungal agent against biofilms formed by Candida albicans resistant strains (a fluconazole-resistant isolate derived from SC5314 and two clinical Candida resistant isolates), was investigated in this study. The inhibitory effects of farnesol on biofilms were examined by XTT assay. The morphological changes and biofilm thicknesses were analyzed by scanning electron microscopy and confocal laser scanning microscopy, respectively. Additionally, the checkerboard microdilution method was used to investigate the interactions between farnesol and antifungals (fluconazole, amphotericin B, caspofungin, itraconazole, terbinafine and 5-flurocytosine) against biofilms. The results showed decreased SMICs of farnesol and thinner biofilms in the farnesol-treated groups, indicating that farnesol inhibited the development of biofilms formed by the resistant strain. Furthermore, there were synergistic effects between farnesol and fluconazole/5-flurocytosine, while there were antagonistic effects between farnesol and terbinafine/itraconazole, respectively, on the biofilms formed by the resistant strains.

Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment

PubMed Central

Vergidis, Pascalis; Clancy, Cornelius J.; Shields, Ryan K.; Park, Seo Young; Wildfeuer, Brett N.; Simmons, Richard L.; Nguyen, M. Hong

2016-01-01

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012–2013. Risk factors for mortality were evaluated using multivariable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC. PMID:27123857

The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides.

PubMed

Serhan, George; Stack, Colin M; Perrone, Gabriel G; Morton, Charles Oliver

2014-05-12

There is a pressing need to identify novel antifungal drug targets to aid in the therapy of life-threatening mycoses and overcome increasing drug resistance. Identifying specific mechanisms of action of membrane-interacting antimicrobial drugs on the model fungus Saccharomyces cerevisiae is one avenue towards addressing this issue. The S. cerevisiae deletion mutants Δizh2, Δizh3, Δaif1 and Δstm1 were demonstrated to be resistant to amphibian-derived antimicrobial peptides (AMPs). The purpose of this study was to examine whether AMPs and polyene antifungals have a similar mode of action; this was done by comparing the relative tolerance of the mutants listed above to both classes of antifungal. In support of previous findings on solid media it was shown that Δizh2 and Δizh3 mutants had increased resistance to both amphotericin B (1-2 μg ml-1) and nystatin (2.5 - 5 μg ml-1) in liquid culture, after acute exposure. However, Δaif1 and Δstm1 had wild-type levels of susceptibility to these polyenes. The generation of reactive oxygen species (ROS) after exposure to amphotericin B was also reduced in Δizh2 and Δizh3. These data indicated that polyene antifungal and AMPs may act via distinct mechanisms of inducing cell death in S. cerevisiae. Further understanding of the mechanism(s) involved in causing cell death and the roles of IZH2 and IZH3 in drug susceptibility may help to inform improved drug design and treatment of fungal pathogens.

A Single Streptomyces Symbiont Makes Multiple Antifungals to Support the Fungus Farming Ant Acromyrmex octospinosus

PubMed Central

Seipke, Ryan F.; Barke, Jörg; Brearley, Charles; Hill, Lionel; Yu, Douglas W.; Goss, Rebecca J. M.; Hutchings, Matthew I.

2011-01-01

Attine ants are dependent on a cultivated fungus for food and use antibiotics produced by symbiotic Actinobacteria as weedkillers in their fungus gardens. Actinobacterial species belonging to the genera Pseudonocardia, Streptomyces and Amycolatopsis have been isolated from attine ant nests and shown to confer protection against a range of microfungal weeds. In previous work on the higher attine Acromyrmex octospinosus we isolated a Streptomyces strain that produces candicidin, consistent with another report that attine ants use Streptomyces-produced candicidin in their fungiculture. Here we report the genome analysis of this Streptomyces strain and identify multiple antibiotic biosynthetic pathways. We demonstrate, using gene disruptions and mass spectrometry, that this single strain has the capacity to make candicidin and multiple antimycin compounds. Although antimycins have been known for >60 years we report the sequence of the biosynthetic gene cluster for the first time. Crucially, disrupting the candicidin and antimycin gene clusters in the same strain had no effect on bioactivity against a co-evolved nest pathogen called Escovopsis that has been identified in ∼30% of attine ant nests. Since the Streptomyces strain has strong bioactivity against Escovopsis we conclude that it must make additional antifungal(s) to inhibit Escovopsis. However, candicidin and antimycins likely offer protection against other microfungal weeds that infect the attine fungal gardens. Thus, we propose that the selection of this biosynthetically prolific strain from the natural environment provides A. octospinosus with broad spectrum activity against Escovopsis and other microfungal weeds. PMID:21857911

Water quality and antifungal susceptibility of opportunistic yeast pathogens from rivers.

PubMed

Monapathi, M E; Bezuidenhout, C C; Rhode, O H J

2017-03-01

Yeasts from water sources have been associated with diseases ranging from superficial mucosal infections to life threatening diseases. The aim of this study was to determine the water quality as well as diversity and antifungal susceptibility of yeasts from two rivers. Yeast levels and physico-chemical parameter data were analyzed by principal component analysis to determine correlations between physico-chemical data and yeast levels. Yeast morphotypes were identified by biochemical tests and 26S rRNA gene sequencing. Disk diffusion antifungal susceptibility tests were conducted. Physico-chemical parameters of the water were within target water quality range (TWQR) for livestock farming. For irrigational use, total dissolved solids and nitrates were not within the TWQR. Yeast levels ranged between 27 ± 10 and 2,573 ± 306 cfu/L. Only non-pigmented, ascomycetous yeasts were isolated. Saccharomyces cerevisiae and Candida glabrata were most frequently isolated. Several other opportunistic pathogens were also isolated. A large number of isolates were resistant to azoles, especially fluconazole, but also to other antifungal classes. Candida species were resistant to almost all the antifungal classes. These water sources are used for recreation and religious as well as for watering livestock and irrigation. Of particular concern is the direct contact of individuals with opportunistic yeast, especially the immune-compromised. Resistance of these yeast species to antifungal agents is a further health concern.

Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital.

PubMed

Gamarra, Soledad; Morano, Susana; Dudiuk, Catiana; Mancilla, Estefanía; Nardin, María Elena; de Los Angeles Méndez, Emilce; Garcia-Effron, Guillermo

2014-10-01

Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis.

Fungal Infections: The Stubborn Cases

PubMed Central

Adam, John E.

1982-01-01

Despite development of numerous antifungal preparations, mycotic infections persist, because of inaccurate diagnosis leading to inappropriate therapy, drug failure, non-compliance or resistance of the organism to antifungal medication. Direct KOH examination is the simplest method of proving the existence of a fungus. Fungal infections tend to be overdiagnosed; disorders which do not improve with three to four weeks of treatment should be reassessed before being labelled ‘stubborn’. Griseofulvin is effective treatment for all dermatophytes, but has certain side effects. Newer topical antifungals are also effective, but no single drug cures all fungal infections. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:20469387

Efficacy of Lippia alba (Mill.) N.E. Brown essential oil and its monoterpene aldehyde constituents against fungi isolated from some edible legume seeds and aflatoxin B1 production.

PubMed

Shukla, Ravindra; Kumar, Ashok; Singh, Priyanka; Dubey, Nawal Kishore

2009-10-31

The present study deals with evaluation of antifungal properties of Lippia alba essential oil (EO) and two of its monoterpene aldehyde constituents against legume-contaminating fungi. Seventeen different fungal species were isolated from 11 varieties of legumes, and aflatoxigenic isolates of Aspergillus flavus were identified. Hydrodistillation method was used to extract the EO from fresh leaves. The GC and GC-MS analysis of EO revealed the monoterpene aldehydes viz. geranial (22.2%) and neral (14.2%) as the major components. The antifungal activity of EO, geranial and neral was evaluated by contact assay on Czapek's-dox agar. The EO (0.25-1 microL/mL) and its two constituents (1 microL/mL) showed remarkable antifungal effects against all the fungal isolates (growth inhibition range 32.1-100%). Their minimal inhibitory (MIC) and fungicidal (MFC) concentrations for A. flavus were lower than those of the systemic fungicide Bavistin. Aflatoxin B(1) (AFB(1)) production by three isolates of A. flavus was strongly inhibited even at the lower fungistatic concentration of EO and its constituents. There was no adverse effect of treatments on seed germination, and rather, there was enhanced seedling growth in the EO-treated seeds. It is concluded that L. alba EO and two of its constituents could be safely used as effective preservative for food legumes against fungal infections and mycotoxins.

Luliconazole, an alternative antifungal agent against Aspergillus terreus.

PubMed

Zargaran, M; Taghipour, S; Kiasat, N; Aboualigalehdari, E; Rezaei-Matehkolaei, A; Zarei Mahmoudabadi, A; Shamsizadeh, F

2017-09-01

Aspergillus terreus is the fourth leading cause of invasive and non-invasive aspergillosis and one of the causative agents of morbidity and mortality among immunocompromised and high-risk patients. A. terreus appears to have increased as a cause of opportunistic fungal infections from superficial to serious invasive infections. Although, invasive aspergillosis is often treated empirically with amphotericin B, most A. terreus isolates are resistant both in vivo and in vitro to some antifungal drugs. In this study, we aimed to evaluate antifungals susceptibility profiles of the different strains of A. terreus against amphotericin B, caspofungin, fluconazole, voriconazole, posaconazole and luliconazole. Forty A. terreus strains originating from environmental sources (air and soil) were identified using by macroscopic and microscopic features. Six antifungals including, amphotericin B, caspofungin, fluconazole, voriconazole, posaconazole and luliconazole were applied for susceptibility tests. Our results show that tested isolates had different susceptibility to antifungals. The lowest MIC GM related to luliconazole (0.00236μg/ml), followed by posaconazole (0.18621μg/ml), voriconazole (0.22925μg/ml), caspofungin (0.86μg/ml), fluconazole (8μg/ml) and amphotericin B (11.12μg/ml). This study demonstrated that luliconazole had an excellent in vitro activity against all tested isolates of A. terreus, with MIC GM 0.00236μg/mL than other tested antifungals. As a result, luliconazole could be a possible alternative antifungal for the treatment of aspergillosis due to A. terreus. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Biocontrol Ability and Action Mechanism of Starmerella bacillaris (Synonym Candida zemplinina) Isolated from Wine Musts against Gray Mold Disease Agent Botrytis cinerea on Grape and Their Effects on Alcoholic Fermentation

PubMed Central

Lemos Junior, Wilson José Fernandes; Bovo, Barbara; Nadai, Chiara; Crosato, Giulia; Carlot, Milena; Favaron, Francesco; Giacomini, Alessio; Corich, Viviana

2016-01-01

Gray mold is one of the most important diseases of grapevine in temperate climates. This plant pathogen affects plant growth and reduces wine quality. The use of yeasts as biocontrol agents to apply in the vineyard have been investigated in recent years as an alternative to agrochemicals. In this work, fermenting musts obtained from overripe grape berries, therefore more susceptible to infection by fungal pathogens such as Botrytis cinerea, were considered for the selection of yeasts carrying antifungal activity. Thirty-six isolates were identified as Starmerella bacillaris, a species recently proven to be of enological interest. Among them 14 different strains were studied and antifungal activity against B. cinerea was demonstrated, for the first time, to be present in S. bacillaris species. The production of volatile organic compounds (VOCs), tested in vitro, was found to be the main responsible of S. bacillaris antifungal effects. All the strains were able to reduce B. cinerea decay on wounded grape berries artificially inoculated with gray mold. The colonization level of wound was very high reaching, after 5 days, a concentration of 106 cells per ml of grape juice obtained after berry crushing. At this cell concentration S. bacillaris strains were used to ferment synthetic and natural musts. The sequential yeast inoculation, performed by adding S. cerevisiae 48 h after S. bacillaris, was needed to complete sugar consumption and determined a significant increase in glicerol content and a reduction of ethanol and acetic acid concentrations. The high wound colonization ability, found in this work, together with the propensity to colonize grape berry and the interesting enological traits possessed by the selected S. bacillaris strains allow the use of this yeast as biocontrol agent on vine and grape berries with possible positive effects on must fermentation, although the presence of S. cerevisiae is needed to complete the fermentation process. This work introduces new possibilities in wine yeast selection programs in order to identify innovative wine yeasts that are simultaneously antifungal agents in vineyards and alternative wine starters for grape must fermentation and open new perspective to a more integrated strategy for increasing wine quality. PMID:27574517

A novel 96-well gel-based assay for determining antifungal activity against filamentous fungi.

PubMed

Troskie, Anscha Mari; Vlok, Nicolas Maré; Rautenbach, Marina

2012-12-01

In recent years the global rise in antibiotic resistance and environmental consciousness lead to a renewed fervour to find and develop novel antibiotics, including antifungals. However, the influence of the environment on antifungal activity is often disregarded and many in vitro assays may cause the activity of certain antifungals to be overestimated or underestimated. The general antifungal test assays that are economically accessible to the majority of scientists primarily rely on visual examination or on spectrophotometric analysis. The effect of certain morphogenic antifungals, which may lead to hyperbranching of filamentous fungi, unfortunately renders these methods unreliable. To minimise the difficulties experienced as a result of hyperbranching, we developed a straightforward, economical 96-well gel-based method, independent of spectrophotometric analysis, for highly repeatable determination of antifungal activity. For the calculation of inhibition parameters, this method relies on the visualisation of assay results by digitisation. The antifungal activity results from our novel micro-gel dilution assay are comparable to that of the micro-broth dilution assay used as standard reference test of The Clinical and Laboratory Standard Institute. Furthermore, our economical assay is multifunctional as it permits microscopic analysis of the preserved assay results, as well as rendering highly reliable data. Copyright © 2012 Elsevier B.V. All rights reserved.

D-Cateslytin: a new antifungal agent for the treatment of oral Candida albicans associated infections.

PubMed

Dartevelle, Pauline; Ehlinger, Claire; Zaet, Abdurraouf; Boehler, Christian; Rabineau, Morgane; Westermann, Benoit; Strub, Jean-Marc; Cianferani, Sarah; Haïkel, Youssef; Metz-Boutigue, Marie-Hélène; Marban, Céline

2018-06-18

The excessive use of antifungal agents, compounded by the shortage of new drugs being introduced into the market, is causing the accumulation of multi-resistance phenotypes in many fungal strains. Consequently, new alternative molecules to conventional antifungal agents are urgently needed to prevent the emergence of fungal resistance. In this context, Cateslytin (Ctl), a natural peptide derived from the processing of Chromogranin A, has already been described as an effective antimicrobial agent against several pathogens including Candida albicans. In the present study, we compared the antimicrobial activity of two conformations of Ctl, L-Ctl and D-Ctl against Candida albicans. Our results show that both D-Ctl and L-Ctl were potent and safe antifungal agents. However, in contrast to L-Ctl, D-Ctl was not degraded by proteases secreted by Candida albicans and was also stable in saliva. Using video microscopy, we also demonstrated that D-Ctl can rapidly enter C. albicans, but is unable to spread within a yeast colony unless from a mother cell to a daughter cell during cellular division. Besides, we revealed that the antifungal activity of D-Ctl could be synergized by voriconazole, an antifungal of reference in the treatment of Candida albicans related infections. In conclusion, D-Ctl can be considered as an effective, safe and stable antifungal and could be used alone or in a combination therapy with voriconazole to treat Candida albicans related diseases including oral candidosis.

Megalanthine, a bioactive sesquiterpenoid from Heliotropium megalanthum, its degradation products and their bioactivities.

PubMed

Macías, Francisco A; Simonet, Ana M; D'Abrosca, Brigida; Maya, Claudia C; Reina, Matías; González-Coloma, Azucena; Cabrera, Raimundo; Giménez, Cristina; Villarroel, Luis

2009-01-01

The new bioactive sesquiterpenoid (3R,6E)-2,6,10-trimethyl-3-(3-p-hydroxyphenylpropanoyloxy)-dodeca-6,11-diene-2,10-diol, named megalanthine, was isolated from the resinous exudates of Heliotropium megalanthum. The degradation products of this compound were identified. Several plant-defensive properties (insecticidal, antifungal, and phytotoxic) were evaluated after obtaining positive results in a preliminary etiolated wheat coleoptile bioassay. This bioassay showed the need to have both the phenolic and sesquiterpene moieties of the natural product present to achieve a biological effect. This result was confirmed in phytotoxicity bioassays. Megalanthine was ruled out as a significant plant-plant defense agent because of its lack of stability. The positive results recorded in the antifungal and antifeedant tests suggest, however, that this chemical is relevant in several ecological interactions involving H. megalanthum.

Effects of twenty-five compounds on four species of aquatic fungi (Saprolegniales) pathogenic to fish

USGS Publications Warehouse

Bailey, T.A.

1984-01-01

Four species of aquatic fungi (Achlya flagellata, A. racemosa, Saprolegnia hypogyna, and S. megasperma) were exposed to 25 chemicals representing seven classes of compounds for 15 and 60 min, in an effort to identify potential fungicidal agents for use in fish culture. The antifungal activity of each chemical was compared with that of malachite green, a reference compound with known fungicidal properties but not registered for fishery use. Six compounds which inhibited fungal growth on artificial media at concentrations of < 100 mg/l (listed in order of decreasing antifungal activity) were the cationics Du-terA? and copper oxychloride sulfate, the amine LesanA?, the amide BAS-389-O1F and the cationics CuprimyxinA? and RoccalA? II. Certain chemicals from these classes of compounds may have promise as aquatic fungicides.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods

PubMed Central

Abreu, D. P. B.; Almeida-Paes, R.; Brilhante, R. S. N.; Chakrabarti, A.; Córdoba, S.; Gonzalez, G. M.; Guarro, J.; Johnson, E. M.; Kidd, S. E.; Pereira, S. A.; Rozental, S.; Szeszs, M. W.; Ballesté Alaniz, R.; Bonifaz, A.; Bonfietti, L. X.; Borba-Santos, L. P.; Capilla, J.; Colombo, A. L.; Dolande, M.; Isla, M. G.; Melhem, M. S. C.; Mesa-Arango, A. C.; Oliveira, M. M. E.; Panizo, M. M.; Pires de Camargo, Z.; Zancope-Oliveira, R. M.; Turnidge, J.

2017-01-01

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy. PMID:28739796

Simple fluorescence-based high throughput cell viability assay for filamentous fungi.

PubMed

Chadha, S; Kale, S P

2015-09-01

Filamentous fungi are important model organisms to understand the eukaryotic process and have been frequently exploited in research and industry. These fungi are also causative agents of serious diseases in plants and humans. Disease management strategies include in vitro susceptibility testing of the fungal pathogens to environmental conditions and antifungal agents. Conventional methods used for antifungal susceptibilities are cumbersome, time-consuming and are not suitable for a large-scale analysis. Here, we report a rapid, high throughput microplate-based fluorescence method for investigating the toxicity of antifungal and stress (osmotic, salt and oxidative) agents on Magnaporthe oryzae and compared it with agar dilution method. This bioassay is optimized for the resazurin reduction to fluorescent resorufin by the fungal hyphae. Resazurin bioassay showed inhibitory rates and IC50 values comparable to the agar dilution method and to previously reported IC50 or MICs for M. oryzae and other fungi. The present method can screen range of test agents from different chemical classes with different modes of action for antifungal activities in a simple, sensitive, time and cost effective manner. A simple fluorescence-based high throughput method is developed to test the effects of stress and antifungal agents on viability of filamentous fungus Magnaporthe oryzae. This resazurin fluorescence assay can detect inhibitory effects comparable to those obtained using the growth inhibition assay with added advantages of simplicity, time and cost effectiveness. This high throughput viability assay has a great potential in large-scale screening of the chemical libraries of antifungal agents, for evaluating the effects of environmental conditions and hyphal kinetic studies in mutant and natural populations of filamentous fungi. © 2015 The Society for Applied Microbiology.

Anti-Candida albicans natural products, sources of new antifungal drugs: A review.

PubMed

Zida, A; Bamba, S; Yacouba, A; Ouedraogo-Traore, R; Guiguemdé, R T

2017-03-01

Candida albicans is the most prevalent fungal pathogen in humans. Due to the development of drug resistance, there is today a need for new antifungal agents for the efficient management of C. albicans infections. Therefore, we reviewed antifungal activity, mechanisms of action, possible synergism with antifungal drugs of all natural substances experimented to be efficient against C. albicans for future. An extensive and systematic review of the literature was undertaken and all relevant abstracts and full-text articles analyzed and included in the review. A total of 111 documents were published and highlighted 142 anti-C. albicans natural products. These products are mostly are reported in Asia (44.37%) and America (28.17%). According to in vitro model criteria, from the 142 natural substances, antifungal activity can be considered as important for 40 (28.20%) and moderate for 24 (16.90%). Sixteen products have their antifungal activity confirmed by in vivo gold standard experimentation. Microbial natural products, source of antifungals, have their antifungal mechanism well described in the literature: interaction with ergosterol (polyenes), inhibition 1,3-β-d-glucan synthase (Echinocandins), inhibition of the synthesis of cell wall components (chitin and mannoproteins), inhibition of sphingolipid synthesis (serine palmitoyltransferase, ceramide synthase, inositol phosphoceramide synthase) and inhibition of protein synthesis (sordarins). Natural products from plants mostly exert their antifungal effects by membrane-active mechanism. Some substances from arthropods are also explored to act on the fungal membrane. Interestingly, synergistic effects were found between different classes of natural products as well as between natural products and azoles. Search for anti-C. albicans new drugs is promising since the list of natural substances, which disclose activity against this yeast is today long. Investigations must be pursued not only to found more new anti-Candida compounds from plants and organisms but also to carried out details on molecules from already known anti-Candida compounds and to more elucidate mechanisms of action. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Preparation and Characterization of Novel Cationic Chitosan Derivatives Bearing Quaternary Ammonium and Phosphonium Salts and Assessment of Their Antifungal Properties.

PubMed

Tan, Wenqiang; Li, Qing; Dong, Fang; Chen, Qiuhong; Guo, Zhanyong

2017-08-31

Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with tricyclohexylphosphine and triphenylphosphine. The structures and properties of synthesized products in the reactions were characterized by FTIR spectroscopy, ¹H-NMR, 31 P-NMR, elemental and thermogravimetric analysis. The antifungal activities of chitosan derivatives against four kinds of phytopathogens, including Phomopsis asparagi , Watermelon fusarium , Colletotrichum lagenarium , and Fusarium oxysporum were tested using the radial growth assay in vitro. The results revealed that the synthesized cationic chitosan derivatives showed significantly improved antifungal efficiency compared to chitosan. It was reasonably suggested that quaternary phosphonium groups enabled the obviously stronger antifungal activity of the synthesized chitosans. Especially, the triphenylphosphonium-functionalized chitosan derivative inhibited the growth of Phomopsis asparagi most effectively, with inhibitory indices of about 80% at 0.5 mg/mL. Moreover, the data demonstrated that the substituted groups with stronger electron-withdrawing ability relatively possessed greater antifungal activity. The results suggest the possibility that cationic chitosan derivatives bearing quaternary phosphonium salts could be effectively employed as novel antifungal biomaterials for application in the field of agriculture.

Antifungal potential of triphala churna ingredients against Aspergillus species associated with them during storage.

PubMed

Gautam, Ajay K; Avasthi, Shubhi; Sharma, Anu; Bhadauria, Rekha

2012-03-01

The present study describes the antifungal potential of fruit and powdered ingredients of triphala churna, i.e. Emblica officinalis (Garetn.) (Amla), Terminalia bellirica (Gaertn.) Roxb. (Baheda) and Terminalia chebula (Retz.) (Harada), collected from the market of Gwalior (M.P.), India. Water extracts of all the fruits and powdered samples were tested (in vitro) for their antifungal activities by poisoned food technique against different Aspergillus species (A. flavus, A. fumigatus, A. versicolor, A. terreus and A. niger) associated with them during storage. All extracts displayed varied levels i.e. very low to very high antifungal activities on four Aspergillus species. The aqueous extracts of fresh fruits (37.96 +/- 7.59%) was observed to be most effective than dry fruits (34.95 +/- 7.59%) and powder (25.07 +/- 6.05%). Terminalia chebula (fresh and dry) extracts were found most active against the four Aspergillus species with 49.15 and 40.8% inhibition, respectively. None of the extracts were found effective against the growth of A. niger. All fruits and powdered aqueous extracts were observed to be ineffective against the A. niger. The variability in antifungal activity of aqueous extracts in the present study may be useful to study the relationship between antifungal potential of herbal drugs and prevalence of fungal contaminant during their storage.

Effects of magnolol and honokiol on adhesion, yeast-hyphal transition, and formation of biofilm by Candida albicans.

PubMed

Sun, Lingmei; Liao, Kai; Wang, Dayong

2015-01-01

The first step in infection by Candida albicans is adhesion to host cells or implanted medical devices and this followed by hyphal growth and biofilm formation. Yeast-to-hyphal transition has long been identified as a key factor in fungal virulence. Following biofilm formation, C. albicans is usually less sensitive or insensitive to antifungals. Therefore, development of new antifungals with inhibitory action on adhesion, yeast-hyphal transition and biofilm formation by C. albicans is very necessary. The effects of magnolol and honokiol on hypha growth were investigated using different induction media. Their inhibitory effects were determined using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide assay, and biofilm thickness and viability were observed by a confocal scanning laser microscope. Mammalian cells were used in adhesion assays. Genes related to hyphae development and cell adhesions were analyzed by real-time reverse transcription-polymerase chain reaction. The exogenous cyclic adenosine monophosphate was used to determine the mechanisms of action of magnolol and honokiol. Caenorhabditis elegans was used as an in vivo model to estimate the antifungal activities of magnolol and honokiol. Magnolol and honokiol inhibited adhesion, the transition from yeast to hypha, and biofilm formation by C. albicans through the Ras1-cAMP-Efg1 pathway. Moreover, magnolol and honokiol prolonged the survival of nematodes infected by C. albicans. Magnolol and honokiol have potential inhibitory effects against biofilm formation by C. albicans. This study provides useful information towards the development of new strategies to reduce the incidence of C. albicans biofilm-associated infection.

Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control.

PubMed

Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S; Westler, William M; Azadi, Parastoo; Nett, Jeniel; Mitchell, Aaron P; Andes, David R

2018-04-03

Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan- Candida species biofilm therapy. IMPORTANCE Candida species, the most common fungal pathogens, frequently grow as a biofilm. These adherent communities tolerate extremely high concentrations of antifungal agents, due in large part, to a protective extracellular matrix. The present studies define the structural, functional, and genetic similarities and differences in the biofilm matrix from the four most common Candida species. Each species synthesizes an extracellular mannan-glucan complex (MGCx) which contributes to sequestration of antifungal drug, shielding the fungus from this external assault. Synthesis of a common polysaccharide backbone appears conserved. However, subtle structural differences in the branching side chains likely rely upon unique modification enzymes, which are species specific. Our findings identify MGCx backbone synthesis as a potential pan- Candida biofilm therapeutic target. Copyright © 2018 Dominguez et al.

In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus

PubMed Central

Seo, Young Ho; Kim, Sung-Su

2015-01-01

2',4'-Dihydroxychalcone (2',4'-DHC) was identified from a heat shock protein 90 (Hsp90)-targeting library as a compound with Hsp90 inhibitory and antifungal effects. In the presence of 2',4'-DHC (8 µg/mL), radial growth of Aspergillus fumigatus was inhibited 20% compared to the control, and green pigmentation was completely blocked. The expression of the conidiation-associated genes abaA, brlA, and wetA was significantly decreased (approximately 3- to 5-fold) by treatment with 2',4'-DHC. The expression of calcineurin signaling components, cnaA and crzA, was also significantly reduced. The inhibitory effects of 2',4'-DHC on metabolic activity and mycelial growth were significantly enhanced by combination treatment with itraconazole and caspofungin. Docking studies indicated that 2',4'-DHC bind to the ATPase domain of Hsp90. These results suggest that 2',4'-DHC act as an Hsp90-calcinurin pathway inhibitor. PMID:26190922

In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus.

PubMed

Seo, Young Ho; Kim, Sung-Su; Shin, Kwang-Soo

2015-06-01

2',4'-Dihydroxychalcone (2',4'-DHC) was identified from a heat shock protein 90 (Hsp90)-targeting library as a compound with Hsp90 inhibitory and antifungal effects. In the presence of 2',4'-DHC (8 µg/mL), radial growth of Aspergillus fumigatus was inhibited 20% compared to the control, and green pigmentation was completely blocked. The expression of the conidiation-associated genes abaA, brlA, and wetA was significantly decreased (approximately 3- to 5-fold) by treatment with 2',4'-DHC. The expression of calcineurin signaling components, cnaA and crzA, was also significantly reduced. The inhibitory effects of 2',4'-DHC on metabolic activity and mycelial growth were significantly enhanced by combination treatment with itraconazole and caspofungin. Docking studies indicated that 2',4'-DHC bind to the ATPase domain of Hsp90. These results suggest that 2',4'-DHC act as an Hsp90-calcinurin pathway inhibitor.

Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

PubMed

Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

2018-06-04

Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

Enhanced UV protection of ketoconazole using Hyptis suaveolens micro emulsion.

PubMed

Khonkarn, Ruttiros; Kittipongpatana, Ornanong S; Boasouna, Vilai; Okonogi, Siriporn

2018-05-01

Ketoconazole is photolabile antifungal drug. Photochemical reactions may decrease its therapeutic effect or induce toxic compounds. The aim of this study was to prepare ketoconazole loaded microemulsion containing H. suaveolens oil with antifungal and antioxidant powers in order to obtain effective antifungal formulation. The release study, antifungal activity and photostability test, were then evaluated. The results showed that optimized Hyptis suaveolens microemulsion for ketoconazole loading was selected through construction of pseudo-ternary phase diagrams. It consisted of 12.5% H. suaveolens oil, 12.5% capryol, 25% tween 80, 25% ethanol and 25% water. Mean globule size was 153 nm, as analyzed by photon correlation spectroscopy. Ketoconazole-loaded Hyptis suaveolens microemulsion and Hyptis suaveolens microemulsion had antifungal activity against Candida albican, Microsporum gypseum and Trichophyton mentagrophyte, showing inhibition zone ranged from 28-37 mm and 23-32 mm, respectively. Ketoconazole was released from Hyptis suaveolens microemulsion more than 90% within 5 days. In the results of photostability test, ketoconazole-loaded Hyptis suaveolens microemulsion gave significantly higher remaining ketoconazole than ketoconazole solution. This study demonstrated that Hyptis suaveolens microemulsion could be used to improve the photoprotection of photolabile drug.

SUSCEPTIBILITY TEST FOR FUNGI: CLINICAL AND LABORATORIAL CORRELATIONS IN MEDICAL MYCOLOGY.

PubMed

Alastruey-Izquierdo, Ana; Melhem, Marcia S C; Bonfietti, Lucas X; Rodriguez-Tudela, Juan L

2015-09-01

During recent decades, antifungal susceptibility testing has become standardized and nowadays has the same role of the antibacterial susceptibility testing in microbiology laboratories. American and European standards have been developed, as well as equivalent commercial systems which are more appropriate for clinical laboratories. The detection of resistant strains by means of these systems has allowed the study and understanding of the molecular basis and the mechanisms of resistance of fungal species to antifungal agents. In addition, many studies on the correlation of in vitro results with the outcome of patients have been performed, reaching the conclusion that infections caused by resistant strains have worse outcome than those caused by susceptible fungal isolates. These studies have allowed the development of interpretative breakpoints for Candida spp. and Aspergillus spp., the most frequent agents of fungal infections in the world. In summary, antifungal susceptibility tests have become essential tools to guide the treatment of fungal diseases, to know the local and global disease epidemiology, and to identify resistance to antifungals.

In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia.

PubMed

James, Jasper Elvin; Santhanam, Jacinta; Lee, Mei Chen; Wong, Choon Xian; Sabaratnam, Parameswari; Yusoff, Hamidah; Tzar, Mohd Nizam; Razak, Mohd Fuat Abdul

2017-04-01

Neoscytalidium dimidiatum is an opportunistic fungus causing cutaneous infections mostly, which are difficult to treat due to antifungal resistance. In Malaysia, N. dimidiatum is associated with skin and nail infections, especially in the elderly. These infections may be mistaken for dermatophyte infections due to similar clinical appearance. In this study, Neoscytalidium isolates from cutaneous specimens, identified using morphological and molecular methods (28 Neoscytalidium dimidiatum and 1 Neoscytalidium sp.), were evaluated for susceptibility towards antifungal agents using the CLSI broth microdilution (M38-A2) and Etest methods. Amphotericin B, voriconazole, miconazole and clotrimazole showed high in vitro activity against all isolates with MIC ranging from 0.0313 to 1 µg/mL. Susceptibility towards fluconazole and itraconazole was noted in up to 10% of isolates, while ketoconazole was inactive against all isolates. Clinical breakpoints for antifungal drugs are not yet available for most filamentous fungi, including Neoscytalidium species. However, the results indicate that clinical isolates of N. dimidiatum in Malaysia were sensitive towards miconazole, clotrimazole, voriconazole and amphotericin B, in vitro.

Inhibitors of the Glyoxylate Cycle Enzyme ICL1 in Candida albicans for Potential Use as Antifungal Agents

PubMed Central

Cheah, Hong-Leong; Lim, Vuanghao; Sandai, Doblin

2014-01-01

Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis. PMID:24781056

Light- and singlet oxygen-mediated antifungal activity of phenylphenalenone phytoalexins.

PubMed

Lazzaro, Alejandra; Corominas, Montserrat; Martí, Cristina; Flors, Cristina; Izquierdo, Laura R; Grillo, Teresa A; Luis, Javier G; Nonell, Santi

2004-07-01

The light-induced singlet oxygen production and antifungal activity of phenylphenalenone phytoalexins isolated from infected banana plants (Musa acuminata) are reported. Upon absorption of light energy all studied phenylphenalenones sensitise the production of singlet oxygen in polar and non-polar media. Antifungal activity of these compounds towards Fusarium oxysporum is enhanced in the presence of light. These results, together with the correlation of IC50 values under illumination with the quantum yield of singlet oxygen production and the enhancing effect of D2O on the antifungal activity, suggest the intermediacy of singlet oxygen produced by electronic excitation of the phenylphenalenone phytoalexins.

In vitro effects of ambroxol on Cryptococcus adherence, planktonic cells, and biofilms.

PubMed

Kong, Qingtao; Du, Xue; Huang, Suyang; Yang, Rui; Zhang, Chengzhen; Shen, Yongnian; Liu, Weida; Sang, Hong

2017-07-01

The antifungal effects of ambroxol (Amb; the metabolite VIII of bromhexine) against Cryptococcus planktonic cells and mature biofilms were investigated in this study. Amb showed antifungal activity against planktonic cells and mature biofilms. Disk diffusion test similarly showed antifungal profile for planktonic cells. Furthermore, Amb was found to be synergetic with fluconazole against planktonic cells and reduced the adherence of cells to polystyrene. Our results suggest that Amb can inhibit cryptococcal cells and biofilms, indicating its potential role in the prevention and treatment of cryptococcosis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Evaluation of antifungal activity of free fatty acids methyl esters fraction isolated from Algerian Linum usitatissimum L. seeds against toxigenic Aspergillus

PubMed Central

Abdelillah, Amrouche; Houcine, Benmehdi; Halima, Dalile; Meriem, Chabane sari; Imane, Zaaboub; Eddine, Smahi Djamal; Abdallah, Moussaoui; Daoudi, Chabane sari

2013-01-01

Objective The aim of this study was to evaluate the antifungal activity of the major fraction of fatty acids methyl esters (FAMEs) isolated from Linum usitatissimum L. seeds oil collected from Bechar department (Algeria). Methods The assessment of antifungal activity was carried out in terms of percentage of radial growth on solid medium (potatoes dextrose agar PDA) and biomass growth inhibition on liquid medium (potatoes dextrose broth PDB) against two fungi. Results The FAMEs was found to be effective in inhibiting the radial mycelial growth of Aspergillus flavus more than Aspergillus ochraceus on all tested concentrations. The highest antifungal index was found to be (54.19%) compared to Aspergillus ochraceus (40.48%). The results of the antifungal activity of the FAMEs inhibition of biomass on liquid medium gave no discounted results, but this does not exclude the antifungal activity. Conclusions We can assume that the observed antifungal potency may be due to the abundance of linoleic and α-linolenic acids in linseed oil which appears to be promising to treat fungal infections, storage fungi and food spoilage in food industry field. PMID:23730556

Candidaemia and antifungal susceptibility testing in a teaching hospital.

PubMed

Tzar, M N; Shamim, A S

2009-03-01

We reviewed cases of candidaemia at Universiti Kebangsaan Malaysia Medical Centre from 1st January 2005 to 30th June 2006. All blood cultures positive for Candida species or its teleomorphs within the study period were identified and antifungal susceptibility testing was performed. Out of 50 blood isolates, 20 (40%) were identified as Candida albicans, 16 (32%) C. tropicalis, five (10%) C. parapsilosis, three (6%) C. famata, two (4%) C. glabrata, two (4%) Pichia ohmeri, one (2%) C. krusei and one (2%) P. etchell/carsonii. Susceptibility to amphotericin B was 100%, fluconazole 90%, itraconazole 40%, ketoconazole 88%, 5-flucytosine 98% and voriconazole 98%.

EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipients.

PubMed

Zaragoza, Rafael; Aguado, José María; Ferrer, Ricard; Rodríguez, Alejandro H; Maseda, Emilio; Llinares, Pedro; Grau, Santiago; Muñoz, Patricia; Fortún, Jesús; Bouzada, Mercedes; Pozo, Juan Carlos Del; León, Rafael

Although over the past decade the management of invasive fungal infection has improved, considerable controversy persists regarding antifungal prophylaxis in solid organ transplant recipients. To identify the key clinical knowledge and make by consensus the high level recommendations required for antifungal prophylaxis in solid organ transplant recipients. Spanish prospective questionnaire, which measures consensus through the Delphi technique, was conducted anonymously and by e-mail with 30 national multidisciplinary experts, specialists in invasive fungal infections from six national scientific societies, including intensivists, anesthetists, microbiologists, pharmacologists and specialists in infectious diseases that responded to 12 questions prepared by the coordination group, after an exhaustive review of the literature in the last few years. The level of agreement achieved among experts in each of the categories should be equal to or greater than 70% in order to make a clinical recommendation. In a second term, after extracting the recommendations of the selected topics, a face-to-face meeting was held with more than 60 specialists who were asked to validate the pre-selected recommendations and derived algorithm. Echinocandin antifungal prophylaxis should be considered in liver transplant with major risk factors (retransplantation, renal failure requiring dialysis after transplantation, pretransplant liver failure, not early reoperation, or MELD>30); heart transplant with hemodialysis, and surgical re-exploration after transplantation; environmental colonization by Aspergillus, or cytomegalovirus (CMV) infection; and pancreas and intestinal transplant in case of acute graft rejection, hemodialysis, initial graft dysfunction, post-perfusion pancreatitis with anastomotic problems or need for laparotomy after transplantation. Antifungal fluconazole prophylaxis should be considered in liver transplant without major risk factors and MELD 20-30, split or living donor, choledochojejunostomy, increased transfusion requirements, renal failure without replacement therapy, early reoperation, or multifocal colonization or infection with Candida; intestinal and pancreas transplant with no risk factors for echinocandin treatment. Liposomal amphotericin B antifungal prophylaxis should be considered in lung transplant (inhalant form) and liver transplant with major risk factors. Antifungal prophylaxis with voriconazole should be considered in lung transplant, and heart transplant with hemodialysis, surgical re-exploration after transplantation, environmental colonization by Aspergillus, or CMV infection. The management of antifungal prophylaxis in solid organ transplant recipients requires the application of knowledge and skills that are detailed in our recommendations and the algorithm developed therein. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Anti-fungal activity of cold and hot water extracts of spices against fungal pathogens of Roselle (Hibiscus sabdariffa) in vitro.

PubMed

Touba, Eslaminejad Parizi; Zakaria, Maziah; Tahereh, Eslaminejad

2012-02-01

Crude extracts of seven spices, viz. cardamom, chilli, coriander, onion, garlic, ginger, and galangale were made using cold water and hot water extraction and they were tested for their anti-fungal effects against the three Roselle pathogens i.e. Phoma exigua, Fusarium nygamai and Rhizoctonia solani using the 'poisoned food technique'. All seven spices studied showed significant anti-fungal activity at three concentrations (10, 20 and 30% of the crude extract) in-vitro. The cold water extract of garlic exhibited good anti-fungal activity against all three tested fungi. In the case of the hot water extracts, garlic and ginger showed the best anti-fungal activity. Of the two extraction methods, cold water extraction was generally more effective than hot water extraction in controlling the pathogens. Against P. exigua, the 10% cold water extracts of galangale, ginger, coriander and cardamom achieved total (100%) inhibition of pathogen mycelial growth. Total inhibition of F. nygamai mycelial growth was similarly achieved with the 10% cold water extracts garlic. Against R. solani, the 10% cold water extract of galangale was effective in imposing 100% inhibition. Accordingly, the 10% galangale extract effectively controlled both P. exigua and R. solani in vitro. None of the hot water extracts of the spices succeeded in achieving 100% inhibition of the pathogen mycelial growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

PubMed Central

Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

2016-01-01

Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies. PMID:27031728

Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

PubMed

Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

2016-01-01

Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

Determination of antifungal susceptibility patterns among the environmental isolates of Aspergillus fumigatus in Iran

PubMed Central

Mohammadi, Faezeh; Dehghan, Parvin; Nekoeian, Shahram; Hashemi, Seyed Jamal

2016-01-01

Background: In recent years, triazole-resistant environmental isolates of Aspergillus fumigatus have emerged in Europe and Asia. Azole resistance has been reported in patients who are treated with long-term azole therapy or exposure of the fungus spores to the azole fungicides used in agriculture. To date, a wide range of mutations in A. fumigatus have been described conferring azole-resistance, which commonly involves modifications in the cyp51A gene. We investigated antifungal susceptibility pattern of environmental isolates of A. fumigatus. Materials and Methods: In this study, 170 environmental samples collected from indoors surfaces of three hospitals in Iran. It was used β-tubulin gene to confirm the all of A. fumigatus isolates, which was identified by conventional methods. Furthermore, the antifungal susceptibility of itraconazole, voriconazole, and posaconazole was investigated using broth microdilution test, according to European Committee on Antimicrobial Susceptibility testing reference method. Results: From a total of 158 environmental molds fungi obtained from the hospitals, 58 isolates were identified as A. fumigatus by amplification of expected size of β-tubulin gene (~500 bp). In this study, in vitro antifungal susceptibility testing has shown that there were not high minimum inhibitory concentration values of triazole antifungals in all of the 58 environmental isolates of A. fumigatus. Conclusion: Our findings demonstrated that there was not azole-resistant among environmental isolates of A. fumigatus. Medical triazoles compounds have structural similarity with triazole fungicide compounds in agriculture, therefore, resistance development through exposure to triazole fungicide compounds in the environment is important but it sounds there is not a serious health problem in drug resistance in environmental isolates in Iran. PMID:27656605

Refractory sporotrichosis due to Sporothrix brasiliensis in humans appears to be unrelated to in vivo resistance.

PubMed

Almeida-Paes, Rodrigo; Oliveira, Manoel Marques Evangelista; Freitas, Dayvison Francis Saraiva; Valle, Antônio Carlos Francesconi do; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely Maria

2017-07-01

Sporotrichosis is a subacute to chronic infection caused by members of the Sporothrix schenckii complex. Itraconazole is the first choice antifungal drug for treating this infection, with terbinafine and potassium iodide as alternatives and amphotericin B used in cases of severe infections. Correlation of antifungal susceptibility data with the clinical outcome of the patients is scarce. The aim of this study was to correlate clinical and mycological data in patients with refractory sporotrichosis. In this work, antifungal susceptibilities, determined according to the reference M38-A2 CLSI protocol, of 25 Sporothrix strains, isolated from seven human cases of sporotrichosis with adversities in the treatment, are presented. Tested drugs included itraconazole, ketoconazole, posaconazole, voriconazole, terbinafine, and amphotericin B. Fungi were identified using the T3B PCR fingerprinting. This method identified all strains as Sporothrix brasiliensis and also demonstrated a high degree of similarity between the strains. In general, voriconazole was ineffective against all strains, and elevated minimal inhibitory concentrations (MICs) were observed for amphotericin B. High itraconazole and terbinafine MICs were not observed in S. brasiliensis isolates from patients of this study. Moreover, a significant increase in itraconazole and terbinafine MIC values from strains isolated from the same patient in different periods was not observed. The results suggest that the antifungal susceptibility to terbinafine and itraconazole determined by the reference method does not play an important role in therapeutic failure of sporotrichosis and that acquisition of resistance during prolonged antifungal treatment is not likely to occur in S. brasiliensis. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil.

PubMed

Favalessa, Olivia Cometti; de Paula, Daphine Ariadne Jesus; Dutra, Valeria; Nakazato, Luciano; Tadano, Tomoko; Lazera, Marcia dos Santos; Wanke, Bodo; Trilles, Luciana; Walderez Szeszs, Maria; Silva, Dayane; Hahn, Rosane Christine

2014-08-13

Cryptococcosis is a systemic fungal infection that affects humans and animals, mainly due to Cryptococcus neoformans and Cryptococcus gattii. Following the epidemic of acquired immunodeficiency syndrome (AIDS), fungal infections by C. neoformans have become more common among immunocompromised patients. Cryptococcus gattii has primarily been isolated as a primary pathogen in healthy hosts and occurs endemically in northern and northeastern Brazil. We to perform genotypic characterization and determine the in vitro susceptibility profile to antifungal drugs of the Cryptococcus species complex isolated from HIV-positive and HIV-negative patients attended at university hospitals in Cuiabá, MT, in the Midwestern region of Brazil. Micromorphological features, chemotyping with canavanine-glycine-bromothymol blue (CGB) agar and genotyping by URA5-RFLP were used to identify the species. The antifungal drugs tested were amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole. Minimum inhibitory concentrations (MICs) were determined according to the CLSI methodology M27-A3. Analysis of samples yelded C. neoformans AFLP1/VNI (17/27, 63.0%) and C. gattii AFLP6/VGII (10/27, 37.0%). The MICs ranges for the antifungal drugs were: amphotericin B (0.5-1 mg/L), fluconazole (1-16 mg/L), flucytosine (1-16 mg/L), itraconazole (0.25-0.12 mg/L) and voriconazole (0.06-0.5 mg/L). Isolates of C. neoformans AFLP1/VNI were predominant in patients with HIV/AIDS, and C. gattii VGII in HIV-negative patients. The genotypes identified were susceptible to the antifungal drugs tested. It is worth emphasizing that AFLP6/VGII is a predominant genotype affecting HIV-negative individuals in Cuiabá. These findings serve as a guide concerning the molecular epidemiology of C. neoformans and C. gattii in the State of Mato Grosso.

Complications of hematopoietic stem transplantation: Fungal infections.

PubMed

Omrani, Ali S; Almaghrabi, Reem S

2017-12-01

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients. The improved diagnostic performance of serum biomarkers such as galactomannan and β-D-glucan, as well as polymerase chain reaction assays has allowed the development of diagnostic-driven antifungal therapy strategies for high risk patients. Diagnostic-driven approaches have resulted in reduced unnecessary antifungal exposure, improved diagnosis of invasive fungal disease, and reduced costs without increased risk of mortality. The appropriateness of diagnostic-driven antifungal strategy for individual HSCT centers depends on the availability and turnaround times for diagnostics, multidisciplinary expertise, and the local epidemiology of invasive fungal infections. Echinocandins are the treatment of choice for invasive candidiasis in most HSCT recipients. Fluconazole may be used for the treatment of invasive candidiasis in hemodynamically stable patients with no prior azole exposure. The primary treatment of choice for invasive aspergillosis is voriconazole. Alternatives include isavuconazole and lipid formulations of amphotericin. Currently available evidence does not support routine primary combination antifungal therapy for invasive aspergillosis. However, combination salvage antifungal therapy may be considered in selected patients. Therapeutic drug monitoring is recommended for the majority of HSCT recipients on itraconazole, posaconazole, or voriconazole. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Functional Assignment of YvgO, a Novel Set of Purified and Chemically Characterized Proteinaceous Antifungal Variants Produced by Bacillus thuringiensis SF361

PubMed Central

Manns, David C.; Churey, John J.

2012-01-01

This study reports a novel class of antifungal protein derived from bacterial origin. Bacillus thuringiensis SF361, the strain also responsible for producing the novel bacteriocin thurincin H, exhibits broad antifungal activity against select members of several fungal genera, including Aspergillus, Byssochlamys, and Penicillium, as well as the pathogenic yeast Candida albicans. Optimal antifungal production and secretion were observed after-log phase growth when incubated at 37°C in a carbohydrate-free growth medium. High-performance liquid chromatography purification was performed after pH-selective ammonium sulfate precipitation and size-exclusion chromatography. Intact mass analysis and peptide mass fingerprinting identified the 13,484-Da protein to be a mass homolog to the YvgO protein construct sequenced from Bacillus cereus AH 1134. Further analysis via amino-terminal sequencing also revealed the existence of four distinct yet equally efficacious YvgO variants differing only within the first four N-terminal residues. YvgO was found to be remarkably stable, maintaining its antifungal activity under a wide pH and temperature range. When assayed against the toxigenic species Byssochlamys fulva H25, the selected primary filamentous fungal indicator, the MIC was estimated to be 1.5 ppm. Candida albicans 3153 was more resistant, exhibiting MICs between 25 and 800 ppm, depending on growth conditions. YvgO is unique among antifungals, showing no known sequential or functional homology to the typical classes of antifungal proteins, including common membrane-acting agents such as cellulases and glucanases. Due to its activity against an array of pathogenic and spoilage fungi, the potentials for clinical, agricultural, and food-processing applications are encouraging. PMID:22307285

Production of ligninolytic enzymes and some diffusible antifungal compounds by white-rot fungi using potato solid wastes as the sole nutrient source.

PubMed

Schalchli, H; Hormazábal, E; Rubilar, O; Briceño, G; Mutis, A; Zocolo, G J; Diez, M C

2017-10-01

The aim of this study was to evaluate the synthesis of ligninolytic enzymes and some diffusible antifungal compounds by white-rot fungi (WRF) using peels or discarded potato as the sole nutrient source. The strain Trametes hirsuta Ru-513 highlighted for its laccase activity (595 ± 33 U l -1 ), which is able to decolourize 87% of an anthraquinone dye using potato peels as the sole nutritional support. A native polyacrylamide gel of laccase proteins showed the presence of two isoenzymes, corresponding to proteins of 56 and 67 kDa, which were detected by SDS-PAGE. The antifungal activity of ethyl acetate extracts was evaluated by the agar diffusion method, where Anthracophyllum discolor Sp4 and Inonotus sp. Sp2 showed the highest inhibition zones of Mucor miehei. The fungal extracts also inhibited Fusarium oxysporum and Botrytis cinerea growth, with inhibition zones of up to 18 mm. The extract with the highest antifungal activity, from A. discolor Sp4 grown in discarded potato medium, was analysed using a gas chromatograph coupled to a mass spectrometer. Among the identified compounds, chlorinated aromatic compounds and veratryl alcohol were the most abundant compounds. The results revealed the relevance of potato waste valorization for the sustainable production of ligninolytic enzymes and antifungal compounds. This study reports the synthesis of ligninolytic enzymes and diffusible antifungal compounds by WRF using potato wastes as the sole nutrient source and suggests a relationship between the enzymatic activity and the synthesis of antifungal compounds. These compounds and the synthesis of halogen compounds by WRF using agro-industrial wastes have been poorly studied before. © 2017 The Society for Applied Microbiology.

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

PubMed

Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

2017-01-01

In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

Quercetin and rutin as potential agents antifungal against Cryptococcus spp.

PubMed

Oliveira, V M; Carraro, E; Auler, M E; Khalil, N M

2016-01-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

PubMed Central

Hein, Kyaw Zaw; Takahashi, Hitoshi; Tsumori, Toshiko; Yasui, Yukihiko; Nanjoh, Yasuko; Toga, Tetsuo; Wu, Zhihong; Grötzinger, Joachim; Jung, Sascha; Wehkamp, Jan; Schroeder, Bjoern O.; Schroeder, Jens M.; Morita, Eishin

2015-01-01

The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn2+-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn2+-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn2+-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi. PMID:26438863

Antifungal and antibacterial activity and chemical composition of polar and non-polar extracts of Athrixia phylicoides determined using bioautography and HPLC

PubMed Central

2013-01-01

Background Athrixia phylicoides DC. (Asteraceae) is used medicinally in South Africa to treat a plethora of ailments, including heart problems, diabetes, diarrhoea, sores and infected wounds. It is also prepared in the form of a tea (hot decoction) taken as a refreshing, pleasant-tasting beverage with commercialization potential. Methods Extracts of the dried ground aerial parts were prepared using organic solvents (diethyl ether, dichloromethane/methanol, ethyl acetate and ethanol) and water. These extracts were subjected to HPLC, TLC and bioautography analysis with the aim of linking a range of peaks visualized in HPLC chromatography profiles to antibacterial and antifungal activity of the same extracts. Results HPLC revealed a group of compounds extracted by more than one solvent. Compounds identified include inositol, caffeic acid, quercetin, kaempferol, apigenin, hymenoxin and oleanolic acid. The organic extracts displayed similar TLC profiles, and bioautography indicated approximately five antibacterial compounds, but only two antifungal compounds in these extracts. Bioautography indicated that cold water extracted the least antimicrobial compounds. Conclusions Several previously unknown compounds were identified in Athrixia phylicoides extracts, and bioautography indicated a number of antibacterial and antifungal compounds. There were notable differences in chemical composition and bioactivity between the organic and aqueous extracts. Further research is necessary to fully characterize the active components of the extracts. PMID:24330447

Expression in Escherichia coli, purification, refolding and antifungal activity of an osmotin from Solanum nigrum

PubMed Central

Campos, Magnólia de A; Silva, Marilia S; Magalhães, Cláudio P; Ribeiro, Simone G; Sarto, Rafael PD; Vieira, Eduardo A; Grossi de Sá, Maria F

2008-01-01

Background Heterologous protein expression in microorganisms may contribute to identify and demonstrate antifungal activity of novel proteins. The Solanum nigrum osmotin-like protein (SnOLP) gene encodes a member of pathogenesis-related (PR) proteins, from the PR-5 sub-group, the last comprising several proteins with different functions, including antifungal activity. Based on deduced amino acid sequence of SnOLP, computer modeling produced a tertiary structure which is indicative of antifungal activity. Results To validate the potential antifungal activity of SnOLP, a hexahistidine-tagged mature SnOLP form was overexpressed in Escherichia coli M15 strain carried out by a pQE30 vector construction. The urea solubilized His6-tagged mature SnOLP protein was affinity-purified by immobilized-metal (Ni2+) affinity column chromatography. As SnOLP requires the correct formation of eight disulfide bonds, not correctly formed in bacterial cells, we adapted an in vitro method to refold the E. coli expressed SnOLP by using reduced:oxidized gluthatione redox buffer. This method generated biologically active conformations of the recombinant mature SnOLP, which exerted antifungal action towards plant pathogenic fungi (Fusarium solani f. sp.glycines, Colletotrichum spp., Macrophomina phaseolina) and oomycete (Phytophthora nicotiana var. parasitica) under in vitro conditions. Conclusion Since SnOLP displays activity against economically important plant pathogenic fungi and oomycete, it represents a novel PR-5 protein with promising utility for biotechnological applications. PMID:18334031

Candidal colonization, strain diversity, and antifungal susceptibility among adult diabetic patients.

PubMed

Al-Attas, Safia A; Amro, Soliman O

2010-01-01

Candidal colonization in diabetics is a matter of debate. The aim of this study is to investigate oral candidal colonization, strain diversity, antifungal susceptibility, and the influence of local and systemic host factors on candidal colonization in adult diabetics. We conducted a case-control study that compared 150 diabetics (49 type 1, 101 type 2) with 50 healthy controls. Two salivary samples were collected, using the oral rinse sampling method: one for salivary flow rate and pH determination, and the other for candidal colonization assessment. The candidal isolates were identified and tested in vitro for antifungal susceptibility using the commercial kit, Candifast. The relationship between specific host factors and candidal colonization was also investigated. Diabetics had a higher candidal carriage rate compared to controls, but not density. Candida albicans was the most frequently isolated species, but diabetics had a variety of other candidal species present. None of the control samples were resistant to any tested antifungal, while the diabetic samples had differing resistances to azole antifungals. Although there was a significant positive correlation between glycemic control and candidal colonization in type 2 diabetics, there was a negative correlation between salivary pH and candidal carriage in the controls versus density in type 2 diabetics. Diabetic patients not only had a higher candidal carriage rate, but also a variety of candidal species that were resistant to azole antifungals. Oral candidal colonization was significantly associated with glycemic control, type of diabetes, and salivary pH.

Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales

PubMed Central

Vitale, Roxana G.; de Hoog, G. Sybren; Schwarz, Patrick; Dannaoui, Eric; Deng, Shuwen; Machouart, Marie; Voigt, Kerstin; van de Sande, Wendy W. J.; Dolatabadi, Somayeh; Meis, Jacques F.

2012-01-01

The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended. PMID:22075600

Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales.

PubMed

Vitale, Roxana G; de Hoog, G Sybren; Schwarz, Patrick; Dannaoui, Eric; Deng, Shuwen; Machouart, Marie; Voigt, Kerstin; van de Sande, Wendy W J; Dolatabadi, Somayeh; Meis, Jacques F; Walther, Grit

2012-01-01

The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended.

Quorum sensing is a key regulator for the antifungal and biocontrol activity of chitinase-producing Chromobacterium sp. C61.

PubMed

Kim, In Seon; Yang, Si Young; Park, Seur Kee; Kim, Young Cheol

2017-01-01

Chromobacterium sp. strain C61 has strong biocontrol activity; however, the genetic and biochemical determinants of its plant disease suppression activity are not well understood. Here, we report the identification and characterization of two new determinants of its biocontrol activity. Transposon mutagenesis was used to identify mutants that were deficient in fungal suppression. One of these mutants had an insertion in a homologue of depD, a structural gene in the dep operon, that encodes a protein involved in non-ribosomal peptide synthesis. In the second mutant, the insertion was in a homologue of the luxI gene, which encodes a homoserine lactone synthase. The luxI - and depD - mutants had no antifungal activity in vitro and a dramatically reduced capacity to suppress various plant diseases in planta. Antifungal production and biocontrol were restored by complementation of the luxI - mutant. Other phenotypes associated with effective biological control, including motility and lytic enzyme secretion, were also affected by the luxI mutation. Biochemical analysis of ethyl acetate extracts of culture filtrates of the mutant and wild-type strains showed that a key antifungal compound, chromobactomycin, was produced by wild-type C61 and the complemented luxI - mutant, but not by the luxI - or depD - mutant. These data suggest that multiple biocontrol-related phenotypes are regulated by homoserine lactones in C61. Thus, quorum sensing plays an essential role in the biological control potential of diverse bacterial lineages. © 2016 BSPP and John Wiley & Sons Ltd.

Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

PubMed

Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

2016-10-01

Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Characterization of volatile constituents from Origanum onites and their antifungal and antibacterial activity.

PubMed

Altintas, Ayhan; Tabanca, Nurhayat; Tyihák, Erno; Ott, Peter G; Móricz, Agnes M; Mincsovics, Emil; Wedge, David E

2013-01-01

Essential oils obtained by hydrodistillation (HD) and microwave-assisted HD (MWHD) of Origanum onites aerial parts were analyzed by GC and GCIMS. Thirty-one constituents representing 98.6% of the water-distilled oil and 52 constituents representing 99.6% of the microwave-distilled oil were identified. Carvacrol (76.8% HD and 79.2% MWHD) and thymol (4.7% HD and 4.4% MWHD) were characterized as major constituents in both essential oils. Separation of carvacrol and thymol was achieved by overpressured layer chromatography. HPTLC and TLC separations were also compared. Essential oils were evaluated for antifungal activity against the strawberry anthracnose-causing fungal plant pathogens Colletotrichum acutatum, C. fragariae, and C. gloeosporioides using a direct overlay bioautography assay. Furthermore, main oil components carvacrol and thymol were then evaluated for antifungal activity; only carvacrol demonstrated nonselective antifungal activity against the three Colletotrichum species. Thymol and carvacrol were subsequently evaluated in a 96-well microdilution broth assay against Phomopsis obscurans, Fusarium oxysporum, three Colletotrichum species, and Botrytis cinerea. No activity was observed against any of the three Colletotrichum species at or below 30 pM. However, thymol demonstrated antifungal activity and produced 31.7% growth inhibition of P. obscurans at 120 h and 0.3 pM, whereas carvacrol appeared inactive. Thymol and carvacrol at 30 pM showed 51.5 and 36.9% growth inhibition of B. cinerea at 72 h. The mechanism of antibacterial activity was studied in a bioautography-based BioArena system. Thymol and carvacrol showed similar inhibition/killing effect against Bacillus subtilis soil bacteria; the action could be enhanced by the formaldehyde generator and transporter copper (II) ions and could be decreased in the presence of L-arginine, a formaldehyde capturer. Results indicated that Origanum essential oils and its major components thymol and carvacrol appear to generate antimicrobial activity through a mechanism of action where formaldehyde and its reaction products are produced.

Wide-range antifungal antagonism of Paenibacillus ehimensis IB-X-b and its dependence on chitinase and beta-1,3-glucanase production.

PubMed

Aktuganov, G; Melentjev, A; Galimzianova, N; Khalikova, E; Korpela, T; Susi, P

2008-07-01

Previously, we isolated a strain of Bacillus that had antifungal activity and produced lytic enzymes with fungicidal potential. In the present study, we identified the bacterium as Paenibacillus ehimensis and further explored its antifungal properties. In liquid co-cultivation assays, P. ehimensis IB-X-b decreased biomass production of several pathogenic fungi by 45%-75%. The inhibition was accompanied by degradation of fungal cell walls and alterations in hyphal morphology. Residual medium from cultures of P. ehimensis IB-X-b inhibited fungal growth, indicating the inhibitors were secreted into the medium. Of the 2 major lytic enzymes, chitinases were only induced by chitin-containing substrates, whereas beta-1,3-glucanase showed steady levels in all carbon sources. Both purified chitinase and beta-1,3-glucanase degraded cell walls of macerated fungal mycelia, whereas only the latter also degraded cell walls of intact mycelia. The results indicate synergism between the antifungal action mechanisms of these enzymes in which beta-1,3-glucanase is the initiator of the cell wall hydrolysis, whereas the degradation process is reinforced by chitinases. Paenibacillus ehimensis IB-X-b has pronounced antifungal activity with a wide range of fungi and has potential as a biological control agent against plant pathogenic fungi.

Characterization of Antifungal Natural Products Isolated from Endophytic Fungi of Finger Millet (Eleusine coracana).

PubMed

Mousa, Walaa Kamel; Schwan, Adrian L; Raizada, Manish N

2016-09-03

Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-Fusarium activity. However, active compounds were isolated from only one strain. The objectives of this study were to confirm the endophytic lifestyle of the three remaining anti-Fusarium isolates, to identify the major underlying antifungal compounds, and to initially characterize the mode(s) of action of each compound. Results of confocal microscopy and a plant disease assay were consistent with the three fungal strains behaving as endophytes. Using bio-assay guided fractionation and spectroscopic structural elucidation, three anti-Fusarium secondary metabolites were purified and characterized. These molecules were not previously reported to derive from fungi nor have antifungal activity. The purified antifungal compounds were: 5-hydroxy 2(3H)-benzofuranone, dehydrocostus lactone (guaianolide sesquiterpene lactone), and harpagoside (an iridoide glycoside). Light microscopy and vitality staining were used to visualize the in vitro interactions between each compound and Fusarium; the results suggested a mixed fungicidal/fungistatic mode of action. We conclude that finger millet possesses fungal endophytes that can synthesize anti-fungal compounds not previously reported as bio-fungicides against F. graminearum.

Anti-Candida and anti-Cryptococcus antifungal produced by marine microorganisms.

PubMed

El Amraoui, B; El Amraoui, M; Cohen, N; Fassouane, A

2014-12-01

In order to search for antifungal from biological origin, we performed a screening of marine microorganisms isolated from seawater, seaweed, sediment and marine invertebrates collected from different coastal areas of the Moroccan Atlantic Ocean. The antifungal activities of these isolates were investigated against the pathogenic yeasts involved in medical mycology. Whole cultures of 34 marine microorganisms were screened for antifungal activities using the method of agar diffusion against four yeasts. The results showed that among the 34 isolates studied, 13 (38%) strains have antifungal activity against at least one out of four yeast species, 11 isolates have anti-Candida albicans CIP 48.72 activity, 12 isolates have anti-C. albicans CIP 884.65 activity, 13 isolates have anti-Cryptococcus neoformans activity and only 6 isolates are actives against Candida tropicalis R2 resistant to nystatin and amphotericin B. Nine isolates showed strong fungicidal activity. Fourteen microorganisms were identified and assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea, and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms could produce more antimicrobials; therefore these marine microorganisms were expected to be potential resources of natural products such as those we research: anti-Candida and anti-Cryptococcus fungicides. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Keratitis-associated fungi form biofilms with reduced antifungal drug susceptibility.

PubMed

Zhang, Xiaoyan; Sun, Xuguang; Wang, Zhiqun; Zhang, Yang; Hou, Wenbo

2012-11-21

To investigate the biofilm-forming capacity of Fusarium solani, Cladosporium sphaerospermum, and Acremonium implicatum, and the activities of antifungal agents against the three keratitis-associated fungi. The architecture of biofilms was analyzed using scanning electron microscopy and confocal scanning laser microscopy (CSLM). Susceptibility against six antifungal drugs was measured using the CLSI M38-A method and XTT reduction assay. Time course analyses of CSLM revealed that biofilm formation occurred in an organized fashion through four distinct developmental phases: adhesion, germling formation, microcolony formation, and biofilm maturation. Scanning electron microscopy revealed that mature biofilms displayed a complex three-dimensional structure, consisting of coordinated network of hyphal structures glued by the extracellular matrix (ECM). The antifungal susceptibility testing demonstrated a time-dependent decrease in efficacy for all six antifungal agents as the complexity of fungal hyphal structures developed. Natamycin (NAT), amphotericin B (AMB), and NAT were the most effective against F. solani, C. sphaerospermum, and A. implicatum biofilm, respectively. Corneal isolates of F. solani, C. sphaerospermum, and A. implicatum could produce biofilms that were resistant to antifungal agents in vitro.

A new antifungal protein and a chitinase with prominent macrophage-stimulating activity from seeds of Phaseolus vulgaris cv. pinto.

PubMed

Ye, X Y; Ng, T B

2002-01-18

From the seeds of the pinto bean (Phaseolus vulgaris cv. pinto), a chitinase and a novel antifungal protein, both with the ability of markedly augmenting nitrite production by murine peritoneal macrophages, were isolated. The antifungal proteins, designated phasein A and phasein B, exhibited molecular weights of 28 and 32 kDa, respectively. Phaseins A and B were adsorbed on Affi-gel blue gel and CM-Sepharose and were eluted as adjacent peaks from CM-Sepharose. Phasein A demonstrated potent antifungal activity toward Fusarium oxysporum and Physalospora piricola. Phasein B was more potent than phasein A toward P. piricola but less potent than phasein A toward F. oxysporum and Rhizoctonia solani. Both antifungal proteins inhibited the activity of HIV-1 reverse transcriptase and translation in a rabbit reticulocyte lysate system, with phasein B being more potent. Nitrite production by mouse macrophages was greatly boosted in the presence of both phaseins A and B, although the effect of phasein A was more prominent. The bioactivities of phaseins were in general potent compared with those of other antifungal proteins.

[Yeast species in vulvovaginitis candidosa].

PubMed

Nemes-Nikodém, Éva; Tamási, Béla; Mihalik, Noémi; Ostorházi, Eszter

2015-01-04

Vulvovaginal candidiasis is the most common mycosis, however, the available information about antifungal susceptibilities of these yeasts is limited. To compare the gold standard fungal culture with a new molecular identification method and report the incidence of yeast species in vulvovaginitis candidosa. The authors studied 370 yeasts isolated from vulvovaginal candidiasis and identified them by phenotypic and molecular methods. The most common species was Candida albicans (85%), followed by Candida glabrata, and other Candida species. At present there are no recommendations for the evaluation of antifungal susceptibility of pathogenic fungal species occurring in vulvovaginal candidiasis and the natural antifungal resistance of the different species is known only. Matrix Assisted Laser Desorption Ionization Time of Flight identification can be used to differentiate the fluconazole resistant Candida dubliniensis and the sensitive Candida albicans strains.

Epidemiology and antifungal susceptibilities of yeast isolates causing invasive infections across urban Beijing, China.

PubMed

Guo, Li-Na; Xiao, Meng; Cao, Bin; Qu, Fen; Zhan, Yu-Liang; Hu, Yun-Jian; Wang, Xin-Ru; Liang, Guo-Wei; Gu, Hai-Tong; Qi, Jun; Yuan, Hui; Min, Rong; Wang, Fei-Yan; Liu, Lin-Juan; Wang, Hai-Bin; Jiang, Wei; Duan, Xue-Guang; Xu, Wen-Jian; Yu, Yan-Hua; Su, Jian-Rong; Zhang, Jian-Zhong; Nong, Jin-Qing; Liu, Shu-Mei; Li, Jun; Liu, Jun-Ting; Yue, Zhi-Gang; Yang, Duo; Guo, Jie; Zhao, Rui; Zhang, Ya-Nan; Yang, Xi-Ming; Liu, Xiao-Qing; Hsueh, Po-Ren; Xu, Ying-Chun

2017-09-01

To investigate the species distribution and antifungal susceptibility profiles of yeast isolates causing invasive infections across Beijing. A total of 1201 yeast isolates recovered from blood and other sterile body fluids were correctly identified by matrix-assisted laser desorption/ionization TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method. Candida (95.5%) remained the most common yeast species isolated; Candida albicans (38.8%) and Candida parapsilosis (22.6%) were the leading species of candidemia. Azole resistances were mainly observed in Candida glabrata and Candida tropicalis isolates. This study outlined the epidemiologic data of invasive yeast infections and highlighted the need for continuous monitoring of azole resistances among C. glabrata and C. tropicalis isolates in Beijing.

Screening of Cyanobacteria (Blue-Green algae) from Rice Paddy Soil for Antifungal Activity against Plant Pathogenic Fungi

PubMed Central

2006-01-01

Soil cyanobacteria isolated from the rice paddy fields of 10 different locations across Korea were evaluated by agar plate diffusion test for antifungal activity. Aqueous, petroleum ether, and methanol extracts from one hundred and forty two cyanobacterial strains belonging to the 14 genera were examined for antifungal properties against seven phytopathogenic fungi causing diseases in hot pepper (Capsicum annuum L). Of total cyanobacteria, nine cyanobacteria (6.34%) exhibited antifungal effects. The nine cyanobacteria selected with positive antifungal activities were two species of Oscillatoria, two of Anabaena, three of Nostoc, one of Nodularia, and one of Calothrix. Alternaria alternata and Botrytis cinerea were inhibited by nine and eight species of cyanobacteria, respectively. Rhizopus stolonifer was suppressed by only methanol extract of Nostoc commune FK-103. In particular, Nostoc commune FK-103 and Oscillatoria tenuis FK-109 showed strong antifungal activities against Phytophthora capsici. Their antifungal activity at the late exponential growth phase is related to the growth temperature and not associated with the growth parameters such as cell biomass and chlorophyll-α concentration. The high inhibition levels of antibiotics were 22.5 and 31.8 mm for N. commune FK-103 and O. tenuis FK-109, respectively. The optimal temperature for antibiotic productivity was 35℃. PMID:24039487

Empiric antifungal therapy and outcomes in extremely low birth weight infants with invasive candidiasis.

PubMed

Greenberg, Rachel G; Benjamin, Daniel K; Gantz, Marie G; Cotten, C Michael; Stoll, Barbara J; Walsh, Michele C; Sánchez, Pablo J; Shankaran, Seetha; Das, Abhik; Higgins, Rosemary D; Miller, Nancy A; Auten, Kathy J; Walsh, Thomas J; Laptook, Abbot R; Carlo, Waldemar A; Kennedy, Kathleen A; Finer, Neil N; Duara, Shahnaz; Schibler, Kurt; Ehrenkranz, Richard A; Van Meurs, Krisa P; Frantz, Ivan D; Phelps, Dale L; Poindexter, Brenda B; Bell, Edward F; O'Shea, T Michael; Watterberg, Kristi L; Goldberg, Ronald N; Smith, P Brian

2012-08-01

To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants. This was a cohort study of infants with a birth weight ≤ 1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI). A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes. Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted. Copyright © 2012 Mosby, Inc. All rights reserved.

Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

PubMed

Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

2016-02-05

Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of polyacetylenic acids from Prunella vulgaris on various plant pathogens.

PubMed

Yoon, M-Y; Choi, G J; Choi, Y H; Jang, K S; Park, M S; Cha, B; Kim, J-C

2010-11-01

This study is aiming at characterizing antifungal substances from the methanol extract of Prunella vulgaris and at investigating those substances' antifungal and antioomycete activities against various plant pathogens. Two polyacetylenic acids were isolated from P. vulgaris as active principles and identified as octadeca-9,11,13-triynoic acid and trans-octadec-13-ene-9,11-diynoic acid. These two compounds inhibited the growth of Magnaporthe oryzae, Rhizoctonia solani, Phytophthora infestans, Sclerotinia sclerotiorum, Fusarium oxysporum f. sp. raphani, and Phytophthora capsici. In addition, these two compounds and the wettable powder-type formulation of an n-hexane fraction of P. vulgaris significantly suppressed the development of rice blast, tomato late blight, wheat leaf rust, and red pepper anthracnose. These data show that the extract of P. vulgaris and two polyacetylenic acids possess antifungal and antioomycete activities against a broad spectrum of tested plant pathogens. This is the first report on the occurrence of octadeca-9,11,13-triynoic acid and trans-octadec-13-ene-9,11-diynoic acid in P. vulgaris and their efficacy against plant diseases. The crude extract containing the two polyacetylenic acids can be used as a natural fungicide for the control of various plant diseases. © 2010 The Authors. © 2010 The Society for Applied Microbiology.

Healthcare-associated outbreaks due to Mucorales and other uncommon fungi.

PubMed

Davoudi, Setareh; Graviss, Linda S; Kontoyiannis, Dimitrios P

2015-07-01

Healthcare-associated outbreaks of fungal infections, especially with uncommon and emerging fungi, have become more frequent in the past decade. Here, we reviewed the history and definition of healthcare-associated outbreaks of uncommon fungal infections and discussed the principles of investigating, containing and treatment of these outbreaks. In case of these uncommon diseases, occurrence of two or more cases in a short period is considered as an outbreak. Contaminated medical devices and hospital environment are the major sources of these outbreaks. Care must be taken to differentiate a real infection from colonization or contamination. Defining and identifying cases, describing epidemiologic feature of cases, finding and controlling the source of the outbreak, treating patients, and managing asymptomatic exposed patients are main steps for outbreak elimination. These fungal outbreaks are not only difficult to detect but also hard to treat. Early initiation of appropriate antifungal therapy is strongly associated with improved outcomes in infected patients. Choice of antifungal drugs should be made based on spectrum, pharmacodynamic and pharmacokinetic characteristics and adverse effects of available drugs. Combination antifungal therapy and surgical intervention may be also helpful in selected cases. A multidisciplinary approach and close collaboration between all key partners are necessary for successful control of fungal outbreaks. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Bacillus sp. BS061 Suppresses Gray Mold and Powdery Mildew through the Secretion of Different Bioactive Substances.

PubMed

Kim, Young-Sook; Song, Ja-Gyeong; Lee, In-Kyoung; Yeo, Woon-Hyung; Yun, Bong-Sik

2013-09-01

A Bacillus sp. BS061 significantly reduced disease incidence of gray mold and powdery mildew. To identify the active principle, the culture filtrate was partitioned between butanol and water. The antifungal activity against B. cinerea was evident in the butanol-soluble portion, and active substances were identified as cyclic lipopeptides, iturin A series, by nuclear magnetic resonance spectrometry (NMR) and mass analysis. Interestingly, antifungal activity against powdery mildew was observed in the water-soluble portion, suggesting that cyclic lipopeptides have no responsibility to suppress powdery mildew. This finding reveals that biocontrol agents of Bacillus origin suppress gray mold and powdery mildew through the secretion of different bioactive substances.

Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity

PubMed Central

Bublitz, Maike; Kjellerup, Lasse; Cohrt, Karen O’Hanlon; Gordon, Sandra; Mortensen, Anne Louise; Clausen, Johannes D.; Pallin, Thomas David; Hansen, John Bondo; Fuglsang, Anja Thoe; Dalby-Brown, William

2018-01-01

We have identified a series of tetrahydrocarbazoles as novel P-type ATPase inhibitors. Using a set of rationally designed analogues, we have analyzed their structure-activity relationship using functional assays, crystallographic data and computational modeling. We found that tetrahydrocarbazoles inhibit adenosine triphosphate (ATP) hydrolysis of the fungal H+-ATPase, depolarize the fungal plasma membrane and exhibit broad-spectrum antifungal activity. Comparative inhibition studies indicate that many tetrahydrocarbazoles also inhibit the mammalian Ca2+-ATPase (SERCA) and Na+,K+-ATPase with an even higher potency than Pma1. We have located the binding site for this compound class by crystallographic structure determination of a SERCA-tetrahydrocarbazole complex to 3.0 Å resolution, finding that the compound binds to a region above the ion inlet channel of the ATPase. A homology model of the Candida albicans H+-ATPase based on this crystal structure, indicates that the compounds could bind to the same pocket and identifies pocket extensions that could be exploited for selectivity enhancement. The results of this study will aid further optimization towards selective H+-ATPase inhibitors as a new class of antifungal agents. PMID:29293507

Selective sweeps in Cryptocercus woodroach antifungal proteins.

PubMed

Velenovsky, Joseph F; Kalisch, Jessica; Bulmer, Mark S

2016-10-01

We identified the antifungal gene termicin in three species of Cryptocercus woodroaches. Cryptocercus represents the closest living cockroach lineage of termites, which suggests that the antifungal role of termicin evolved prior to the divergence of termites from other cockroaches. An analysis of Cryptocercus termicin and two β-1,3-glucanase genes (GNBP1 and GNBP2), which appear to work synergistically with termicin in termites, revealed evidence of selection in these proteins. We identified the signature of past selective sweeps within GNBP2 from Cryptocercus punctulatus and Cryptocercus wrighti. The signature of past selective sweeps was also found within termicin from Cryptocercus punctulatus and Cryptocercus darwini. Our analysis further suggests a phenotypically identical variant of GNBP2 was maintained within Cryptocercus punctulatus, Cryptocercus wrighti, and Cryptocercus darwini while synonymous sites diverged. Cryptocercus termicin and GNBP2 appear to have experienced similar selective pressure to that of their termite orthologues in Reticulitermes. This selective pressure may be a result of ubiquitous entomopathogenic fungal pathogens such as Metarhizium. This study further reveals the similarities between Cryptocercus woodroaches and termites.

Identification and Characterization of Lipopeptides from Bacillus subtilis B1 Against Sapstain Fungus of Rubberwood Through MALDI-TOF-MS and RT-PCR.

PubMed

Sajitha, K L; Dev, Suma Arun; Maria Florence, E J

2016-07-01

Bacillus subtilis is a potent biocontrol agent producing a wide array of antifungal lipopeptides for the inhibition of fungal growth. B. subtilis B1 isolated from market-available compost provided an efficient control of rubberwood sapstain fungus, Lasiodiplodia theobromae. The current study is aimed to identify and characterize the lipopeptides responsible for the biocontrol of rubberwood sapstain fungus by Bacillus subtilis B1. The bacterial whole-cell surface extract from the dual culture of B. subtilis B1 and sapstain fungus (L. theobromae) was analysed using MALDI-TOF-MS. The protonated as well as sodium, potassium adducts of homologues of iturin C, surfactin, bacillomycin D and fengycin A and B were identified and expression of the lipopeptide biosynthetic genes could be confirmed through RT-PCR. This is the first report of mycobacillin and trimethylsilyl derivative of bacilysin during antagonism through MALDI-TOF-MS. MALDI-TOF-MS with RT-PCR offered easy platforms to characterize the antifungal lipopeptides. The identification of antifungal lipopeptides can lead to the formulation of prospective biocontrol by-products which have wide-scale utility.

Effects of Magnolol and Honokiol on Adhesion, Yeast-Hyphal Transition, and Formation of Biofilm by Candida albicans

PubMed Central

Sun, Lingmei; Liao, Kai; Wang, Dayong

2015-01-01

Background The first step in infection by Candida albicans is adhesion to host cells or implanted medical devices and this followed by hyphal growth and biofilm formation. Yeast-to-hyphal transition has long been identified as a key factor in fungal virulence. Following biofilm formation, C. albicans is usually less sensitive or insensitive to antifungals. Therefore, development of new antifungals with inhibitory action on adhesion, yeast-hyphal transition and biofilm formation by C. albicans is very necessary. Methods The effects of magnolol and honokiol on hypha growth were investigated using different induction media. Their inhibitory effects were determined using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide assay, and biofilm thickness and viability were observed by a confocal scanning laser microscope. Mammalian cells were used in adhesion assays. Genes related to hyphae development and cell adhesions were analyzed by real-time reverse transcription-polymerase chain reaction. The exogenous cyclic adenosine monophosphate was used to determine the mechanisms of action of magnolol and honokiol. Caenorhabditis elegans was used as an in vivo model to estimate the antifungal activities of magnolol and honokiol. Results and conclusions Magnolol and honokiol inhibited adhesion, the transition from yeast to hypha, and biofilm formation by C. albicans through the Ras1-cAMP-Efg1 pathway. Moreover, magnolol and honokiol prolonged the survival of nematodes infected by C. albicans. Magnolol and honokiol have potential inhibitory effects against biofilm formation by C. albicans. General Significance This study provides useful information towards the development of new strategies to reduce the incidence of C. albicans biofilm-associated infection. PMID:25710475

In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palicz, Zoltán; Jenes, Ágnes; Gáll, Tamás

2013-05-15

The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg{sup −1} daily, for 2 weeks. Even at the highest concentration – a concentration highly toxic in vitro for all affected molds – used, animals neither died due tomore » the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. - Highlights: • PAF, the antifungal protein of Penicillium chrysogenum, was not toxic in mice. • Its intranasal application didn't induce pathological reactions in the lung. • PAF retained its antifungal activity in lung extracts. • Its application on the skin did not cause inflammation.« less

Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids.

PubMed

Mor, Visesato; Rella, Antonella; Farnoud, Amir M; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B; Wiederhold, Nathan P; Fothergill, Annette W; Kirkpatrick, William R; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L; Luberto, Chiara; Nimrichter, Leonardo; Del Poeta, Maurizio

2015-06-23

Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N'-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N'-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals. Copyright © 2015 Mor et al.

Characterization of the antifungal activity of Lactobacillus harbinensis K.V9.3.1Np and Lactobacillus rhamnosus K.C8.3.1I in yogurt.

PubMed

Delavenne, Emilie; Cliquet, Sophie; Trunet, Clément; Barbier, Georges; Mounier, Jérôme; Le Blay, Gwenaëlle

2015-02-01

Few antifungal protective cultures adapted to fermented dairy products are commercially available because of the numerous constraints linked to their market implementation. Consumer's demand for naturally preserved food products is growing and the utilization of lactic acid bacteria is a promising way to achieve this goal. In this study, using a 2(5-1) factorial fractional design, we first evaluated the effects of fermentation time, of initial sucrose concentration and of the initial contamination amount of a spoilage yeast, on antifungal activities of single and mixed cultures of Lactobacillus rhamnosus K.C8.3.1I and Lactobacillus harbinensis K.V9.3.1Np in yogurt. L. harbinensis K.V9.3.1Np, the most relevant strain with regard to antifungal activity was then studied to determine its minimal inhibitory inoculation rate, its antifungal stability during storage and its impact on yogurt organoleptic properties. We showed that L. harbinensis K.V9.3.1Np maintained a stable antifungal activity over time, which was not affected by initial sucrose, nor by a reduction of the fermentation time. This inhibitory activity was an all-or-nothing phenomenon. Once L. harbinensis K.V9.3.1Np reached a population of ∼ 2.5 × 10(6) cfu/g of yogurt at the time of contamination, total inhibition of the yeast was achieved. We also showed that an inoculation rate of 5 × 10(6) cfu/ml in milk had no detrimental effect on yogurt organoleptic properties. In conclusion, L. harbinensis K.V9.3.1Np is a promising antifungal bioprotective strain for yogurt preservation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ecdysteroids in Sida tuberculata R.E. Fries (Malvaceae): chemical composition by LC-ESI-MS and selective anti-Candida krusei activity.

PubMed

da Rosa, Hemerson Silva; de Camargo, Vanessa Brum; Camargo, Graziela; Garcia, Cássia V; Fuentefria, Alexandre M; Mendez, Andreas S L

2015-09-01

Sida tuberculata is found in a region of South America and has traditionally been consumed as an infusion or tea. The chemical composition and antifungal activity of aqueous infusions from leaves and roots were investigated. LC-ESI-MS mass spectra were successfully obtained and used to identify four ecdysteroids: 20-hydroxyecdysone-3-O-β-D-glycopyranoside, 20-hydroxyecdysone, 20-hydroxyecdysone-3-O-β-D-xylose and a hydroxyecdysterone derivative. The in vitro antifungal activity was studied, and the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were established against Candida krusei isolates. The antibiofilm activity was evaluated by the determination of the biofilm removal efficiency in contaminated central venous catheter (CVC) coupons. The preparations exhibited antifungal activity against the species tested, with MICs ranging from 3.90 to 62.50 μg/ml. The infusion removed the C. krusei biofilm after 90 min of exposure. The observed bioactivity and composition of ecdysteroids will contribute to the future development of antifungal substances for clinical use or as food additives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical composition and in vitro antifungal and antioxidant activity of the essential oil and methanolic extract of Teucrium sauvagei Le Houerou.

PubMed

Salah, K Bel Hadj; Mahjoub, M A; Chaumont, J P; Michel, L; Millet-Clerc, J; Chraeif, I; Ammar, S; Mighri, Z; Aouni, M

2006-10-01

The chemical composition and the in vitro antifungal and antioxidant activity of the essential oil and the methanolic leaf extracts of Teucrium sauvagei Le Houerou, an endemic medicinal plant growing in Tunisia, have been studied. More than 35 constituents having an abundance >or=0.2% were identified in the oil. beta-Eudesmol, T-cadinol, alpha-thujene, gamma-cadinene, and sabinene were the prevalent constituents. Results of the antifungal activity tests indicated that the methanolic extract inhibited the in vitro growth of seven dermatophytes, whereas the essential oil showed average inhibition against only three dermatophytes. In vitro antioxidant properties of the essential oil and the methanolic extract were determined by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid)) assays and compared to those of the synthetic antioxidant Trolox. Due to their antifungal and antioxidant properties, the essential oil and the methanolic extract of T. sauvagei may be of use as natural preservative ingredients in food and/or pharmaceutical industries.

Antifungal effects of Lavandula binaludensis and Cuminum cyminum essential oils against Candida albicans strains isolated from patients with recurrent vulvovaginal candidiasis.

PubMed

Minooeianhaghighi, M H; Sepehrian, L; Shokri, H

2017-03-01

Recurrent vulvovaginal candidiasis (RVVC), which affects approximately 5% of women of reproductive age, is defined as 4 or more episodes of symptomatic Candida vaginitis within a year. The purposes of this study were to determine the chemical compositions and antifungal susceptibility of Cuminum cyminum (C. cyminum) and Lavandula binaludensis (L. binaludensis) essential oils and their combination against Candida albicans (C. albicans) strains isolated from patients with RVVC. C. albicans isolates were identified via germ tube test, CHROMagar and RapID Yeast Plus System. The essential oils were obtained by hydrodistillation in a Clevenger apparatus and analyzed by gas chromatography-mass spectroscopy (GC-MS). The broth microdilution method was used as antifungal susceptibility test (CLSI-M27-A3). The GC-MS analysis allowed 13 components to be determined; the main components of C. cyminum and L. binaludensis essential oils were γ-terpinene (21.07%) and 1,8-cineole (71.56%), respectively. L. binaludensis and C. cyminum oils were effective in inhibiting C. albicans growth at mean concentrations of 7.91±1.61μg/mL and 8.00±1.89μg/mL, respectively. In addition, the combination of C. cyminum with L. binaludensis oils were more active causing inhibition in all C. albicans isolates, with concentrations varying from 3.90 to 11.71μg/mL (mean value: 7.22±1.69μg/mL). The results suggested the potential substitution of the antifungal chemicals by C. cyminum and L. binaludensis essential oils as natural inhibitors to control the growth of the most important pathogenic Candida species and alternative therapies for RVVC. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Essential oils from Schinus species of northwest Argentina: Composition and antifungal activity.

PubMed

Sampietro, Diego A; Belizana, Maria Melina E; Baptista, Zareath P Terán; Vattuone, Marta A; Catalán, Cesar A N

2014-07-01

The composition of the essential oils from leaves (Sal) and fruits of S. areira (Saf), and fruits of S. fasciculatus (Sff) and S. gracilipes (Sgf) were analyzed by GC/MS. The major compounds identified were sabinene (26.0 +/- 0.5%), bicyclogermacrene (14.5 +/- 0.4%), and E-citral (6.7+/- 0.2%) in Sal oil, limonene (27.7 +/- 0.7%), sabinene (16.0+/- 0.5%), beta-phellandrene (14.6 +/- 0.8%) and bicyclogermacrene (8.1 +/- 0.2%) in Saf oil, sabinene (22.7 +/- 0.6%), alpha-phellandrene (18.7 +/- 0.3%), beta-phellandrene (15.7 +/- 0.4%), and bicyclogermacrene (8.1 +/- 0.2%) in Sff oil and beta-pinene (25.4 +/- 0.8%), alpha-pinene (24.7 +/- 0.7%), and sabinene (13.6 +/- 0.4%) in Sgf oil.The antifungal activity of the four oils was evaluated on strains of Fusarium verticillioides and F. graminearum, and the results compared with the effect of epoxyconazole, pyraclostrobin and thyme oil. The Sff oil had the highest antifungal activity among the Schinus oils tested, with MIC100 (F. graminearum) = 6 per thousand and MIC100 (F. verticillioides) = 12 per thousand. A principal component analysis suggests that 9 constituents (alpha-thujene, alpha-terpinene, p-cymene, gamma-terpinene, terpinolene, 1-terpineol, alpha-calacorene, alpha-phellandrene, and terpinen-4-ol) explain the higher antifungal effect of Sff. The MIC100s of Schinus oils were on average 30-60 and 8.5-17 fold lower than those obtained for thyme oil on F. verticillioides and F. graminearum, respectively. In the case of commercial fungicides, their MIC100s were three orders of magnitude lower than those of Schinus oils. The last ones showed an additive interaction when assayed in mixtures with the commecial fungicides and thyme oil. The results suggest that the doses of fungicides required for control of the Fusarium species can be reduced when they are assayed in mixtures with the Schinus oils.

Steroid acne vs. Pityrosporum folliculitis: the incidence of Pityrosporum ovale and the effect of antifungal drugs in steroid acne.

PubMed

Yu, H J; Lee, S K; Son, S J; Kim, Y S; Yang, H Y; Kim, J H

1998-10-01

Steroid acne is a folliculitis that can result from systemic or topical administration of steroid, and has been described as showing a similar clinical picture to Pityrosporum folliculitis, but there have been few reports about the incidence of Pityrosporum ovale and the effect of antimycotic drugs in steroid acne and other acneiform eruptions. Our purpose was to describe the association between steroid acne and P. ovale, and to confirm the superior efficacy of oral antifungal drugs over anti-acne drugs in the treatment of steroid acne. The history, clinical features direct microscopy, histopathologic analysis, and therapeutic results of 125 cases with steroid acne or other acneiform eruptions were described and compared. Over 80% of patients with acneiform eruption receiving systemic steroid revealed significant numbers of P. ovale in the lesional follicle. Furthermore, oral antifungal drug (itraconazole) showed significantly better clinical and mycologic effects than any other group of medications used in this study. Steroid acne and other acneiform eruptions showing discrete follicular papules and/or pustules localized to the upper trunk and acneiform facial skin lesions associated with multiple acneiform lesions on the body in the summer period should be suspected as Pityrosporum folliculitis. In addition, oral antifungal drugs recommended for Pityrosporum folliculitis; however, it will require a larger case-control study to confirm the superiority of antifungal therapy over anti-acne treatment.

Whey permeate fermented with kefir grains shows antifungal effect against Fusarium graminearum.

PubMed

Gamba, Raúl Ricardo; De Antoni, Graciela; Peláez, Angela León

2016-05-01

The objective of the work reported here was to study the antifungal capability of cell-free supernatants obtained from whey permeates after fermentation by the kefir grains CIDCA AGK1 against Fusarium graminearum growth and zearalenone (ZEA) production. The assays were performed in order to study the conidial germination inhibition -in liquid media- and the effect on fungal growth rate and the Latency phase -in solid media. We observed that fermented supernatants of pH 3·5 produced the highest percentages of inhibition of conidial germination. The dilution and, particularly, alkalinisation of them led to the gradual loss of antifungal activity. In the fungal inhibition assays on plates we found that only the highest proportion of supernatant within solid medium had significant antifungal activity, which was determined as fungicidal. There was no ZEA biosynthesis in the medium with the highest proportion of supernatant, whereas at lower concentrations, the mycotoxin production was strain-dependent. From the results obtained we concluded that kefir supernatants had antifungal activity on the F. graminearum strains investigated and inhibited mycotoxin production as well, but in a strain-dependent fashion. The present work constitutes the first report of the effect of the products obtained from the kefir-grain fermentation of whey permeates - a readily available by-product of the dairy industry - on F. graminearum germination, growth, and toxin production.

Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp.

PubMed

Sardi, Janaína de Cássia Orlandi; Gullo, Fernanda Patrícia; Freires, Irlan Almeida; Pitangui, Nayla de Souza; Segalla, Maicon Petrônio; Fusco-Almeida, Ana Marisa; Rosalen, Pedro Luiz; Regasini, Luís Octávio; Mendes-Giannini, Maria José Soares

2016-12-01

We tested the antifungal potential of caffeic acid and 8 of its derivative esters against Candidaalbicans ATCC 90028 and 9 clinical isolatesand carried out a synergism assay with fluconazole and nystatin. Propyl caffeate (C3) showed the best antifungal activity against the tested strains. When in combination, C3 markedly reduced the MIC of fluconazole and nystatin with synergistic effect up to 64-fold. Finally, C3 showed a high IC 50 value and selective indexagainst oral keratinocytes, demonstrating low toxicity against this cell type and selectivity for yeast cells. Further research should confirm its antifungal potential for development of combined therapy to treat C. albicans infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Asymmetric total synthesis of 6-Tuliposide B and its biological activities against tulip pathogenic fungi.

PubMed

Shigetomi, Kengo; Omoto, Shoko; Kato, Yasuo; Ubukata, Makoto

2011-01-01

The structure-activity relationship was investigated to evaluate the antifungal activities of tuliposides and tulipalins against tulip pathogenic fungi. 6-Tuliposide B was effectively synthesized via the asymmetric Baylis-Hillman reaction. Tuliposides and tulipalins showed antifungal activities against most of the strains tested at high concentrations (2.5 mM), while Botrytis tulipae was resistant to tuliposides. Tulipalin formation was involved in the antifungal activity, tulipalin A showed higher inhibitory activity than 6-tuliposide B and tulipalin B. Both the tuliposides and tulipalins showed pigment-inducing activity against Gibberella zeae and inhibitory activity against Fusarium oxysporum f. sp tulipae. These activities were induced at a much lower concentration (0.05 mM) than the antifungal MIC values.

Augmenting the efficacy of antifungal intervention via chemo-biological approaches

USDA-ARS?s Scientific Manuscript database

Mycotic infection is becoming a serious health problem since effective antifungal agents for control of pathogenic fungi, especially drug-resistant pathogens, is often very limited. Fungal resistance to antimycotic agents frequently involves mutations caused by environmental stressors. In fungal pat...

Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species.

PubMed

Teodoro, Valter Luis Iost; Gullo, Fernanda Patrícia; Sardi, Janaína de Cássia Orlandi; Torres, Edson Maria; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

2013-01-01

The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B) independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%), Cryptococcus gattii (5.2%), Cryptococcus ater (3.5%), Cryptococcus laurentti (1.7%), and Cryptococcus luteolus (1.7%). A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

Systemic antifungal therapy for tinea capitis in children: An abridged Cochrane Review.

PubMed

Chen, Xiaomei; Jiang, Xia; Yang, Ming; Bennett, Cathy; González, Urbà; Lin, Xiufang; Hua, Xia; Xue, Siliang; Zhang, Min

2017-02-01

The comparative efficacy and safety profiles of systemic antifungal drugs for tinea capitis in children remain unclear. We sought to assess the effects of systemic antifungal drugs for tinea capitis in children. We used standard Cochrane methodological procedures. We included 25 randomized controlled trials with 4449 participants. Terbinafine and griseofulvin had similar effects for children with mixed Trichophyton and Microsporum infections (risk ratio 1.08, 95% confidence interval 0.94-1.24). Terbinafine was better than griseofulvin for complete cure of T tonsurans infections (risk ratio 1.47, 95% confidence interval 1.22-1.77); griseofulvin was better than terbinafine for complete cure of infections caused solely by Microsporum species (risk ratio 0.68, 95% confidence interval 0.53-0.86). Compared with griseofulvin or terbinafine, itraconazole and fluconazole had similar effects against Trichophyton infections. All included studies were at unclear or high risk of bias. Lower quality evidence resulted in a lower confidence in the estimate of effect. Significant clinical heterogeneity existed across studies. Griseofulvin or terbinafine are both effective; terbinafine is more effective for T tonsurans and griseofulvin for M canis infections. Itraconazole and fluconazole are alternative but not optimal choices for Trichophyton infections. Optimal regimens of antifungal agents need further studies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

New ion-exchanged zeolite derivatives: antifungal and antimycotoxin properties against Aspergillus flavus and aflatoxin B1

NASA Astrophysics Data System (ADS)

Savi, Geovana D.; Cardoso, Willian A.; Furtado, Bianca G.; Bortolotto, Tiago; Da Agostin, Luciana O. V.; Nones, Janaína; Torres Zanoni, Elton; Montedo, Oscar R. K.; Angioletto, Elidio

2017-08-01

Zeolites are microporous crystalline hydrated aluminosilicates with absorbent and catalytic properties. This material can be used in many applications in stored-pest management such as: pesticide and fertilizer carriers, animal feed additives, mycotoxin binders and food packaging materials. Herein, four 4A zeolite forms were prepared by ion-exchange and their antifungal effect against Aspergillus flavus was highlighted. Additionally, the antimycotoxin activity and the aflatoxin B1 (AFB1) adsorption capacity of these zeolites as well as their toxic effects on Artemia sp. were investigated. The ion-exchanged zeolites with Li+ and Cu2+ showed the best antifungal activity against A. flavus, including effects on conidia germination and hyphae morphological alterations. Regarding to antimycotoxin activity, all zeolite samples efficiently inhibited the AFB1 production by A. flavus. However, the ion-exchanged zeolites exhibited better results than the 4A zeolite. On the other hand, the AFB1 adsorption capacity was only observed by the 4A zeolite and zeolite-Li+. Lastly, our data showed that all zeolites samples used at effective concentrations for antifungal and antimycotoxin assays (2 mg ml-1) showed no toxic effects towards Artemia sp. Results suggest that some these ion-exchanged zeolites have great potential as an effective fungicide and antimycotoxin agent for agricultural and food safety applications.

Species distribution and antifungal susceptibility patterns of Candida isolates from a public tertiary teaching hospital in the Eastern Cape Province, South Africa.

PubMed

Mnge, P; Okeleye, B I; Vasaikar, S D; Apalata, T

2017-05-15

Candida species are the leading cause of invasive fungal infections, and over the past decade there has been an increased isolation of drug resistant Candida species. This study aimed to identify the species distribution of Candida isolates and to determine their unique antifungal susceptibility and resistance patterns. During a cross-sectional study, 209 Candida isolates (recovered from 206 clinical samples) were collected and their species distribution was determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa) was used to determine minimum inhibitory concentrations (MICs) to azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes (amphotericin B) and flucytosine. Four species of Candida were isolated, of which C. albicans was the most frequent, isolated in 45.4% (95/209) of the isolates, followed by C. glabrata: 31.1% (65/209). The MICs of the different antifungal drugs varied amongst the species of Candida. From the 130 isolates tested for MICs, 90.77% (112/130) were susceptible to all antifungal drugs and 6.9% (9/130) of the isolates were multi-drug resistant. C. dubliniensis (n=2) isolates were susceptible to all the above mentioned antifungal drugs. There was no significant difference in species distribution amongst clinical specimens and between patients' genders (P>0.05). An increase in MIC values for fluconazole and flucytosine towards the resistance range was observed. To our knowledge, this is the first report on surveillance of Candida species distribution and antifungal susceptibility at a public tertiary teaching hospital in Eastern Cape, South Africa.

Antifungal resistance: current trends and future strategies to combat

PubMed Central

Wiederhold, Nathan P

2017-01-01

Antifungal resistance represents a major clinical challenge to clinicians responsible for treating invasive fungal infections due to the limited arsenal of systemically available antifungal agents. In addition current drugs may be limited by drug–drug interactions and serious adverse effects/toxicities that prevent their prolonged use or dosage escalation. Fluconazole resistance is of particular concern in non-Candida albicans species due to the increased incidence of infections caused by these species in different geographic locations worldwide and the elevated prevalence of resistance to this commonly used azole in many institutions. C. glabrata resistance to the echinocandins has also been documented to be rising in several US institutions, and a higher percentage of these isolates may also be azole resistant. Azole resistance in Aspergillus fumigatus due to clinical and environmental exposure to this class of agents has also been found worldwide, and these isolates can cause invasive infections with high mortality rates. In addition, several species of Aspergillus, and other molds, including Scedosporium and Fusarium species, have reduced susceptibility or pan-resistance to clinically available antifungals. Various investigational antifungals are currently in preclinical or clinical development, including several of them that have the potential to overcome resistance observed against the azoles and the echinocandins. These include agents that also target ergosterol and b-glucan biosynthesis, as well as compounds with novel mechanisms of action that may also overcome the limitations of currently available antifungal classes, including both resistance and adverse effects/toxicity. PMID:28919789

Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity.

PubMed

Mesa-Arango, Ana Cecilia; Montiel-Ramos, Jehidys; Zapata, Bibiana; Durán, Camilo; Betancur-Galvis, Liliana; Stashenko, Elena

2009-09-01

Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 microg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 microg/mL for A. fumigatus and 39.7 microg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 microg/mL for C. krusei and 176.8 microg/mL for A. fumigatus.

Management of symptomatic erosive-ulcerative lesions of oral lichen planus in an adult Egyptian population using Selenium-ACE combined with topical corticosteroids plus antifungal agent

PubMed Central

Belal, Mahmoud Helmy

2015-01-01

Aim: Oral lichen planus (OLP) is a chronic mucocutaneous disease with an immunological etiology. This study was conducted to evaluate the effect of selenium combined with Vitamins A, C & E (Selenium-ACE) in the treatment of erosive-ulcerative OLP as an adjunctive to topical corticosteroids plus antifungal agent. Subjects and Methods: Thirty patients with a confirmed clinical and histopathologic diagnosis of OLP participated in this clinical trial. Patients were randomly allocated into one of three groups and treated as follows: (I) Topical corticosteroids, (II) topical corticosteroids plus antifungal, and (III) SE-ACE combined with topical corticosteroids plus antifungal. The patients were followed for 6 weeks. The pain and severity of the lesions were recorded at the initial and follow-up visits. All recorded data were analyzed using paired t-test and ANOVA test. A P ≤ 0.05 was considered significant. Results: The experimental groups showed a marked reduction in pain sensation and size of lesions, particularly in the final follow-up period, but there was no significant difference between the first two Groups I and II. However, healing of lesions and improvement of pain sensation was effective in Group III since a significant difference was found favoring Group III over both Groups I and II. Conclusion: No significant difference was found in treating erosive-ulcerative lesions of OLP by topical corticosteroids alone or combined with antifungal. However, when using SE-ACE in combination with topical corticosteroids plus antifungal, this approach may be effective in managing ulcerative lesions of OLP; but more research with a larger sample size and a longer evaluation period may be recommended. PMID:26681847

Use of alcohol vinegar in the inhibition of Candida spp. and its effect on the physical properties of acrylic resins.

PubMed

de Castro, Ricardo Dias; Mota, Ana Carolina Loureiro Gama; de Oliveira Lima, Edeltrudes; Batista, André Ulisses Dantas; de Araújo Oliveira, Julyana; Cavalcanti, Alessandro Leite

2015-04-28

Given the high prevalence of oral candidiasis and the restricted number of antifungal agents available to control infection, this study investigated the in vitro antifungal activity of alcohol vinegar on Candida spp. and its effect on the physical properties of acrylic resins. Tests to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of vinegar alcohol (0.04 g/ml of acetic acid) and nystatin (control) were performed. The antifungal activity of alcohol vinegar was assessed through microbial growth kinetic assays and inhibition of Candida albicans adhesion to acrylic resin at different intervals of time. Surface roughness and color of the acrylic resin were analyzed using a roughness meter and color analyzer device. Alcohol vinegar showed MIC75% and MFC62.5% of 2.5 mg/ml, with fungicidal effect from 120 min, differing from nystatin (p < 0.0001), which showed fungistatic effect. Alcohol vinegar caused greater inhibition of C. albicans adhesion to the acrylic resin (p ≤ 0.001) compared to nystatin and did not change the roughness and color parameters of the material. Alcohol vinegar showed antifungal properties against Candida strains and caused no physical changes to the acrylic resin.

Reveromycins A and B from Streptomyces sp. 3–10: Antifungal Activity against Plant Pathogenic Fungi In vitro and in a Strawberry Food Model System

PubMed Central

Lyu, Ang; Liu, Hao; Che, Hongjie; Yang, Long; Zhang, Jing; Wu, Mingde; Chen, Weidong; Li, Guoqing

2017-01-01

This study was conducted to determine the antifungal activity of the metabolites from Streptomyces sp. 3–10, and to purify and identify the metabolites. Meanwhile, the taxonomic status of strain 3–10 was re-evaluated. The cultural filtrates of strain 3–10 in potato dextrose broth were extracted with ethyl acetate. The resulting crude extract at 1 and 5 μg/ml inhibited growth of 22 species in 18 genera of plant pathogenic fungi and Oomycetes, accounting for 92% of the total 24 tested species, suggesting that it has a wide antifungal spectrum. Two compounds were purified from the crude extract and were identified as reveromycins A and B, which demonstrated high antifungal activity against Botrytis cinerea, Mucor hiemails, Rhizopus stolonifer, and Sclerotinia sclerotiorum under acidic pH conditions. Both the crude extract and reveromycin A from strain 3–10 at 10, 50, and 100 μg/ml showed high efficacy in suppression of strawberry fruit rot caused by the above-mentioned four pathogens. The efficacy was comparable to that of corresponding commercial fungicides (pyrimethanil, captan, dimetachlone) used in management of these pathogens. Morphological, physiological, and phylogenetic characterization showed that strain 3–10 is closely related to Streptomyces yanglinensis 1307T, representing a novel phylotype in that species. This study reported a new strain with reveromycins-producing capability. The finding is important for further exploitation of reveromycins for agricultural use. PMID:28421050

Effect of essential oils prepared from Thai culinary herbs on sessile Candida albicans cultures.

PubMed

Hovijitra, Ray S; Choonharuangdej, Suwan; Srithavaj, Theerathavaj

2016-01-01

Although medicinal herbs with fungicidal effects have been ubiquitously employed in traditional medicine, such effects of culinary herbs and spices still have to be elucidated. Therefore, it is noteworthy to determine the antifungal efficacy of some edible herbs used in Thai cuisine against sessile Candida albicans cultures, and to inquire if they can be further utilized as naturally-derived antifungals. Fourteen essential oils extracted from Thai culinary herbs and spices were tested for their antifungal activity against C. albicans using the agar disk diffusion method followed by broth micro-dilution method for the determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration. The oils with potent antifungal effects against planktonic fungi were then assessed for their effect against sessile fungus (adherent organisms and established biofilm culture). MIC of the oils against sessile C. albicans was evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide reduction assay. All selected culinary herbs and spices, except galangal, garlic, and turmeric, exhibited inhibitory effects on planktonic yeast cells. Cinnamon bark and sweet basil leaf essential oils exhibited potent fungicidal effect on planktonic and sessile fungus. Sessile MICs were 8-16 times higher than planktonic MICs. Consequently, both cinnamon bark and sweet basil leaf herbal oils seem to be highly effective anti-Candida choices. (J Oral Sci 58, 365-371, 2016).

Host immune reactivity determines the efficacy of combination immunotherapy and antifungal chemotherapy in candidiasis.

PubMed

Mencacci, A; Cenci, E; Bacci, A; Bistoni, F; Romani, L

2000-02-01

In immunocompetent mice with candidiasis, successful therapy with amphotericin B and fluconazole relies on the induction of protective, T helper (Th) type 1 responses, an effect potentiated by concomitant interleukin (IL)-4 neutralization. To assess the therapeutic efficacy of combined treatments with antifungals and immunomodulators in conditions of immunosuppression, leukopenic or neutropenic mice with disseminated candidiasis were treated with amphotericin B or fluconazole alone or in combination with soluble IL-4 receptor (sIL-4R) or recombinant (r) IL-12 or IL-10 neutralizing monoclonal antibodies. We found that (1) the synergistic effect of sIL-4R and antifungals is retained in immunocompromised mice; (2) synergism with amphotericin B was superior to that with fluconazole, particularly in leukopenic mice; (3) rIL-12 synergized with fluconazole in neutropenic mice; and (4) IL-10 neutralization was always of limited efficacy. This study indicates that the therapeutic efficacy of antifungals is differentially potentiated by cytokines or cytokine antagonists and is influenced by host immune reactivity.

Evaluation of Antifungal Effect of Silver Nanoparticles Against Microsporum canis, Trichophyton mentagrophytes and Microsporum gypseum

PubMed Central

Ayatollahi Mousavi, Seyyed Amin; Salari, Samira; Hadizadeh, Sanaz

2015-01-01

Background Dermatophytosis is the common cutaneous infections in humans and animals, which is caused by the keratinophylic fungus called dermatophytes. In recent years, drugs resistance in pathogenic fungi, including dermatophyte strains to the current antifungals have been increased. Objectives The aim of this study was to evaluate the antifungal efficacy of AgNPs against Microsporum canis, Trichophyton mentagrophytes , and Microsporum gypseum. Materials and Methods The antifungal susceptibility of nanosilver particles compared with griseofulvin (GR). Its efficacy was investigated against three strains of dermatophytes by both agar dilution and broth microdilution test (BMD). Results The average minimum inhibitory concentration (MIC) AgNPs on M. canis, T. mentagrophytes and M. gypseum were 200, 180 and 170 μg.mL-1, respectively. Whereas these strains showed MIC of 25, 100 and 50 μg.mL-1 for GR. Conclusions Our finding indicated that the AgNPs was less active than GR but it had anti-dermatophytic effect. PMID:28959308

Antifungal-protein production in maize (Zea mays) suspension cultures.

PubMed

Perri, Fabio; Della Penna, Serena; Rufini, Francesca; Patamia, Maria; Bonito, Mariantonietta; Angiolella, Letizia; Vitali, Alberto

2009-04-01

The growing emergency due to the phenomenon of drug resistance to micro-organisms has pushed forward the search for new potential drug alternatives to those already in use. Plants represent a suitable source of new antifungal molecules, as they produce a series of defensive proteins. Among them are the PRPs (pathogenesis-related proteins), shown to be effective in vitro against human pathogens. An optimized and established cell-suspension culture of maize (Zea mays) was shown to constitutively secrete in the medium a series of PRPs comprising the antifungal protein zeamatin (P33679) with a final yield of approx. 3 mg/litre. The in-vitro-produced zeamatin possessed antifungal activity towards a clinical strain of the human pathogenic yeast Candida albicans, an activity comparable with the one reported for the same protein extracted from maize seeds. Along with zeamatin, other PRPs were expressed: a 9 kDa lipid-transfer protein, a 26 kDa xylanase inhibitor and a new antifungal protein, PR-5. A fast, two-step chromatographic procedure was set up allowing the complete purification of the proteins considered, making this cell line a valuable system for the production of potential antifungal agents in a reliable and easy way.

Effectiveness of Natural Antifungal Compounds in Controlling Infection by Grapevine Trunk Disease Pathogens through Pruning Wounds

PubMed Central

Cobos, Rebeca; Mateos, Rosa María; Álvarez-Pérez, José Manuel; Olego, Miguel Angel; Sevillano, Silvia; González-García, Sandra; Garzón-Jimeno, Enrique

2015-01-01

Grapevine trunk fungal pathogens, such as Diplodia seriata and Phaeomoniella chlamydospora, can infect plants through pruning wounds. They cause grapevine trunk diseases and are involved in grapevine decline. Accordingly, the protection of pruning wounds is crucial for the management of grapevine trunk diseases. The efficacy of different natural antifungals in inhibiting the growth of several fungi causing grapevine trunk diseases was evaluated in vitro. The fungi showing greater in vitro efficacy were tested on autoclaved grape wood assays against D. seriata and P. chlamydospora. Based on results from these assays, chitosan oligosaccharide, vanillin, and garlic extract were selected for further evaluation on pruning wounds inoculated with D. seriata and P. chlamydospora in field trials. A significant decrease in plant mortality was observed after 2 years of growth in the plants treated with the different natural antifungals compared to the mortality rate observed in infected plants that were not treated with antifungals. Also, the infection rate for the inoculated pathogens was significantly reduced in plants treated with the selected natural antifungals. Therefore, natural antifungals represent a promising alternative for disease control and could provide significant economic benefits for the grape-growing industry. PMID:26162882

In vitro antifungal susceptibility profiles of Cryptococcus species isolated from HIV-associated cryptococcal meningitis patients in Zimbabwe.

PubMed

Nyazika, Tinashe K; Herkert, Patricia F; Hagen, Ferry; Mateveke, Kudzanai; Robertson, Valerie J; Meis, Jacques F

2016-11-01

Cryptococcus neoformans is the leading cause of cryptococcosis in HIV-infected subjects worldwide. Treatment of cryptococcosis is based on amphotericin B, flucytosine, and fluconazole. In Zimbabwe, little is known about antifungal susceptibility of Cryptococcus. Sixty-eight genotyped Cryptococcus isolates were tested for antifungal profiles. Amphotericin B, isavuconazole, and voriconazole showed higher activity than other triazoles. Fluconazole and flucytosine were less effective, with geometric mean MICs of 2.24 and 2.67mg/L for C. neoformans AFLP1/VNI, 1.38 and 1.53mg/L for C. neoformans AFLP1A/VNB/VNII and AFLP1B/VNII, and 1.85 and 0.68mg/L for Cryptococcus tetragattii, respectively. A significant difference between flucytosine geometric mean MICs of C. neoformans and C. tetragattii was observed (P=0.0002). The majority of isolates (n=66/68; 97.1%) had a wild-type MIC phenotype of all antifungal agents. This study demonstrates a favorable situation with respect to the tested antifungals agents. Continued surveillance of antifungal susceptibility profiles is important due to the high burden of cryptococcosis in Africa. Copyright © 2016 Elsevier Inc. All rights reserved.

Keratomycosis due to Tintelnotia destructans refractory to common therapy treated successfully with systemic and local terbinafine in combination with polyhexamethylene biguanide.

PubMed

Behrens-Baumann, Wolfgang J; Hofmüller, Wolfram; Tammer, Ina; Tintelnot, Kathrin

2018-04-28

To report on a wearer of rigid gas-permeable contact lenses with a keratomycosis due to Tintelnotia-a new genus of Phaeosphaeriaceae-treated with terbinafine and polyhexamethylene biguanide. Chart review of a patient with fungal keratitis treated additionally with systemic and topical terbinafine 0.25% after symptoms increased under conventional antimycotic therapy with voriconazole. Antifungal susceptibility had been tested in vitro. After starting an additional treatment with systemic and topical terbinafine, the severe corneal infection was sufficiently resolved. The drug was well tolerated without any neurological, dermatological or gastroenterological problems. Terbinafine revealed a marked in vitro antifungal activity of 0.12 µg/ml. The fungus was identified as Tintelnotia destructans. Terbinafine might be considered as a therapeutic option in severe cases of fungal keratitis refractory to common antifungal therapy.

Mycotoxins and antifungal drug interactions: implications in the treatment of illnesses due to indoor chronic toxigenic mold exposures.

PubMed

Anyanwu, Ebere C; Campbell, Andrew W; Ehiri, John E

2004-03-12

Chronic exposure to toxigenic molds in water-damaged buildings is an indoor environmental health problem to which escalating health and property insurance costs are raising a statewide concern in recent times. This paper reviews the structural and functional properties of mycotoxins produced by toxigenic molds and their interactive health implications with antifungal drugs. Fundamental bases of pathophysiological, neurodevelopmental, and cellular mechanisms of mycotoxic effects are evaluated. It is most likely that the interactions of mycotoxins with antifungal drugs may, at least in part, contribute to the observable persistent illnesses, antifungal drug resistance, and allergic reactions in patients exposed to chronic toxigenic molds. Safe dose level of mycotoxin in humans is not clear. Hence, the safety regulations in place at the moment remain inconclusive, precautionary, and arbitrary. Since some of the antifungal drugs are derived from molds, and since they have structural and functional groups similar to those of mycotoxins, the knowledge of their interactions are important in enhancing preventive measures.

Optimization of antifungal production by an alkaliphilic and halotolerant actinomycete, Streptomyces sp. SY-BS5, using response surface methodology.

PubMed

Souagui, Y; Tritsch, D; Grosdemange-Billiard, C; Kecha, M

2015-06-01

Optimization of medium components and physicochemical parameters for antifungal production by an alkaliphilic and salt-tolerant actinomycete designated Streptomyces sp. SY-BS5; isolated from an arid region in south of Algeria. The strain showed broad-spectrum activity against pathogenic and toxinogenic fungi. Identification of the actinomycete strain was realized on the basis of 16S rRNA gene sequencing. Antifungal production was optimized following one-factor-at-a-time (OFAT) and response surface methodology (RSM) approaches. The most suitable medium for growth and antifungal production was found using one-factor-at-a-time methodology. The individual and interaction effects of three nutritional variables, carbon source (glucose), nitrogen source (yeast extract) and sodium chloride (NaCl) were optimized by Box-Behnken design. Finally, culture conditions for the antifungal production, pH and temperature were studied and determined. Analysis of the 16S rRNA gene sequence (1454 nucleotides) assigned this strain to Streptomyces genus with 99% similarity with Streptomyces cyaneofuscatus JCM4364(T), the most closely related. The results of the optimization study show that concentrations 3.476g/L of glucose, 3.876g/L of yeast extract and 41.140g/L of NaCl are responsible for the enhancement of antifungal production by Streptomyces sp. SY-BS5. The preferable culture conditions for antifungal production were pH 10, temperature 30°C for 09 days. This study proved that RSM is usual and powerful tool for the optimization of antifungal production from actinomycetes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014.

PubMed

Morrissey, C O; Gilroy, N M; Macesic, N; Walker, P; Ananda-Rajah, M; May, M; Heath, C H; Grigg, A; Bardy, P G; Kwan, J; Kirsa, S W; Slavin, M; Gottlieb, T; Chen, S

2014-12-01

Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

PubMed Central

Pierce, Christopher G.; Lopez-Ribot, Jose L.

2014-01-01

Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

Characterization of Scedosporium apiospermum Glucosylceramides and Their Involvement in Fungal Development and Macrophage Functions

PubMed Central

Rollin-Pinheiro, Rodrigo; Liporagi-Lopes, Livia Cristina; de Meirelles, Jardel Vieira; de Souza, Lauro M.; Barreto-Bergter, Eliana

2014-01-01

Scedosporium apiospermum is an emerging fungal pathogen that causes both localized and disseminated infections in immunocompromised patients. Glucosylceramides (CMH, GlcCer) are the main neutral glycosphingolipids expressed in fungal cells. In this study, glucosylceramides (GlcCer) were extracted and purified in several chromatographic steps. Using high-performance thin layer chromatography (HPTLC) and electrospray ionization mass spectrometry (ESI-MS), N-2′-hydroxyhexadecanoyl-1-β-D-glucopyranosyl-9-methyl-4,8-sphingadienine was identified as the main GlcCer in S. apiospermum. A monoclonal antibody (Mab) against this molecule was used for indirect immunofluorescence experiments, which revealed that this CMH is present on the surface of the mycelial and conidial forms of S. apiospermum. Treatment of S. apiospermum conidia with the Mab significantly reduced fungal growth. In addition, the Mab also enhanced the phagocytosis and killing of S. apiospermum by murine cells. In vitro assays were performed to evaluate the CMHs for their cytotoxic activities against the mammalian cell lines L.929 and RAW, and an inhibitory effect on cell proliferation was observed. Synergistic in vitro interactions were observed between the Mab against GlcCer and both amphotericin B (AmB) and itraconazole. Because Scedosporium species develop drug resistance, the number of available antifungal drugs is limited; our data indicate that combining immunotherapy with the available drugs might be a viable treatment option. These results suggest that in S. apiospermum, GlcCer are most likely cell wall components that are targeted by antifungal antibodies, which directly inhibit fungal development and enhance macrophage function; furthermore, these results suggest the combined use of monoclonal antibodies against GlcCer and antifungal drugs for antifungal immunotherapy. PMID:24878570

Characterization of Scedosporium apiospermum glucosylceramides and their involvement in fungal development and macrophage functions.

PubMed

Rollin-Pinheiro, Rodrigo; Liporagi-Lopes, Livia Cristina; de Meirelles, Jardel Vieira; Souza, Lauro M de; Barreto-Bergter, Eliana

2014-01-01

Scedosporium apiospermum is an emerging fungal pathogen that causes both localized and disseminated infections in immunocompromised patients. Glucosylceramides (CMH, GlcCer) are the main neutral glycosphingolipids expressed in fungal cells. In this study, glucosylceramides (GlcCer) were extracted and purified in several chromatographic steps. Using high-performance thin layer chromatography (HPTLC) and electrospray ionization mass spectrometry (ESI-MS), N-2'-hydroxyhexadecanoyl-1-β-D-glucopyranosyl-9-methyl-4,8-sphingadienine was identified as the main GlcCer in S. apiospermum. A monoclonal antibody (Mab) against this molecule was used for indirect immunofluorescence experiments, which revealed that this CMH is present on the surface of the mycelial and conidial forms of S. apiospermum. Treatment of S. apiospermum conidia with the Mab significantly reduced fungal growth. In addition, the Mab also enhanced the phagocytosis and killing of S. apiospermum by murine cells. In vitro assays were performed to evaluate the CMHs for their cytotoxic activities against the mammalian cell lines L.929 and RAW, and an inhibitory effect on cell proliferation was observed. Synergistic in vitro interactions were observed between the Mab against GlcCer and both amphotericin B (AmB) and itraconazole. Because Scedosporium species develop drug resistance, the number of available antifungal drugs is limited; our data indicate that combining immunotherapy with the available drugs might be a viable treatment option. These results suggest that in S. apiospermum, GlcCer are most likely cell wall components that are targeted by antifungal antibodies, which directly inhibit fungal development and enhance macrophage function; furthermore, these results suggest the combined use of monoclonal antibodies against GlcCer and antifungal drugs for antifungal immunotherapy.

Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008-2011.

PubMed

Cleveland, Angela Ahlquist; Farley, Monica M; Harrison, Lee H; Stein, Betsy; Hollick, Rosemary; Lockhart, Shawn R; Magill, Shelley S; Derado, Gordana; Park, Benjamin J; Chiller, Tom M

2012-11-15

Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008-2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992-1993; Baltimore, 1998-2000). We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged <1 year; Atlanta, 34.3; Baltimore, 46.2). In both locations compared with prior surveillance, adjusted incidence significantly declined for infants of both black and white race (Atlanta: black risk ratio [RR], 0.26 [95% confidence interval {CI}, .17-.38]; white RR: 0.19 [95% CI, .12-.29]; Baltimore: black RR, 0.38 [95% CI, .22-.64]; white RR: 0.51 [95% CI: .29-.90]). Prevalence of fluconazole resistance (7%) was unchanged compared with prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were multidrug resistant to both fluconazole and an echinocandin. We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed.

Changes in Incidence and Antifungal Drug Resistance in Candidemia: Results From Population-Based Laboratory Surveillance in Atlanta and Baltimore, 2008–2011

PubMed Central

Cleveland, Angela Ahlquist; Farley, Monica M.; Harrison, Lee H.; Stein, Betsy; Hollick, Rosemary; Lockhart, Shawn R.; Magill, Shelley S.; Derado, Gordana; Park, Benjamin J.; Chiller, Tom M.

2015-01-01

Background Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. Methods We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008–2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992–1993; Baltimore, 1998–2000). Results We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged <1 year; Atlanta, 34.3; Baltimore, 46.2). In both locations compared with prior surveillance, adjusted incidence significantly declined for infants of both black and white race (Atlanta: black risk ratio [RR], 0.26 [95% confidence interval {CI}, .17–.38]; white RR: 0.19 [95% CI, .12–.29]; Baltimore: black RR, 0.38 [95% CI, .22–.64]; white RR: 0.51 [95% CI: .29–.90]). Prevalence of fluconazole resistance (7%) was unchanged compared with prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were multidrug resistant to both fluconazole and an echinocandin. Conclusions We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed. PMID:22893576

P&T Committee review of fluconazole: an effective alternative to antifungal therapy.

PubMed

Neu, H C; Bennett, J E; Bodey, G P; Rubin, R H; Schentag, J J; Sugar, A M

1990-03-01

Fluconazole is a new antifungal agent available in both oral and parenteral formulations. According to the experts in this roundtable discussion, fluconazole represents a major clinical advance in the treatment of candidiasis and cryptococcosis in cancer patients, patients with AIDS, organ transplant recipients, and other patients at risk for opportunistic mycoses. The pharmacokinetic profile for fluconazole permits infrequent dosing and also makes it ideal for tissue site infections. Fluconazole's low toxicity gives it an advantage over currently available antifungal therapy and will permit prompt presumptive treatment of selected infections.

Time-Kill Kinetics and In Vitro Antifungal Susceptibility of Non-fumigatus Aspergillus Species Isolated from Patients with Ocular Mycoses.

PubMed

Öz, Yasemin; Özdemir, Havva Gül; Gökbolat, Egemen; Kiraz, Nuri; Ilkit, Macit; Seyedmousavi, Seyedmojtaba

2016-04-01

Aspergillus species can cause ocular morbidity and blindness, and thus, appropriate antifungal therapy is needed. We investigated the in vitro activity of itraconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and amphotericin B against 14 Aspergillus isolates obtained from patients with ocular mycoses, using the CLSI reference broth microdilution methodology. In addition, time-kill assays were performed, exposing each isolate separately to 1-, 4-, and 16-fold concentrations above the minimum inhibitory concentration (MIC) of each antifungal agent. A sigmoid maximum-effect (E max) model was used to fit the time-kill curve data. The drug effect was further evaluated by measuring an increase/decrease in the killing rate of the tested isolates. The MICs of amphotericin B, itraconazole, voriconazole, and posaconazole were 0.5-1.0, 1.0, 0.5-1.0, and 0.25 µg/ml for A. brasiliensis, A. niger, and A. tubingensis isolates, respectively, and 2.0-4.0, 0.5, 1.0 for A. flavus, and 0.12-0.25 µg/ml for A. nomius isolates, respectively. A. calidoustus had the highest MIC range for the azoles (4.0-16.0 µg/ml) among all isolates tested. The minimum effective concentrations of caspofungin and anidulafungin were ≤0.03-0.5 µg/ml and ≤0.03 µg/ml for all isolates, respectively. Posaconazole demonstrated maximal killing rates (E(max) = 0.63 h(-1), r(2) = 0.71) against 14 ocular Aspergillus isolates, followed by amphotericin B (E(max) = 0.39 h(-1), r(2) = 0.87), voriconazole (E(max) = 0.35 h(-1), r(2) = 0.098), and itraconazole (E(max) = 0.01 h(-1), r(2) = 0.98). Overall, the antifungal susceptibility of the non-fumigatus Aspergillus isolates tested was species and antifungal agent dependent. Analysis of the kinetic growth assays, along with consideration of the killing rates, revealed that posaconazole was the most effective antifungal against all of the isolates.

Thermo-stability, dose effects and shelf-life of antifungal compounds produced by the symbiotic bacterium Xenorhabdus szentirmaii

USDA-ARS?s Scientific Manuscript database

Xenorhabdus spp bacteria are associated with Steinernematid nematodes and produce antifungal metabolites that protect nematode-infected cadavers from fungal colonization. Previous work demonstrated concentrated or cell-free metabolites of X. szentirmaii were toxic to fungal phytopathogens. We prepar...

Antifungal activity of geldanamycin alone or in combination with fluconazole against Candida species.

PubMed

Zhang, Jinqing; Liu, Wei; Tan, Jingwen; Sun, Yi; Wan, Zhe; Li, Ruoyu

2013-04-01

A standardized broth microdilution method was used to test the antifungal activity of geldanamycin (GA), an inhibitor of heat shock protein 90 (Hsp90), alone or in combination with the antifungal agent fluconazole (FLC) against 32 clinical isolates of Candida spp. In addition, a disk diffusion test was also used to evaluate the antifungal effect of these two drugs against Candida spp. by measuring the inhibition zone diameters. We found that the range of minimal inhibitory concentrations (MICs) for GA alone against Candida spp. was 3.2-12.8 mg/L and the geometric mean of MICs was 6.54 mg/L. In addition, the combination of GA with FLC showed synergistic effects in vitro against 2 FLC-susceptible and 6 FLC-resistant isolates of C. albicans. As for the other isolates, indifference but no antagonism was observed. In the disk diffusion assay, the diameter of inhibition zones for FLC combined with GA against FLC-resistant C. albicans isolates was 30 mm, while no inhibition was observed with FLC alone. These results demonstrate that GA possesses antifungal activity against Candida spp., and the combination of GA with FLC shows in vitro synergistic activity against some C. albicans isolates, especially those resistant to FLC.

Trypanocide, cytotoxic, and antifungal activities of Momordica charantia.

PubMed

Santos, Karla K A; Matias, Edinardo F F; Sobral-Souza, Celestina E; Tintino, Saulo R; Morais-Braga, Maria F B; Guedes, Glaucia M M; Santos, Francisco A V; Sousa, Ana Carla A; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique D M

2012-02-01

Chagas disease, caused by Trypanosoma cruzi, is a public health problem. Currently, chemotherapy is the only available treatment for this disease, and the drugs used, nifurtimox and benzonidazol, present high toxicity levels. An alternative for replacing these drugs are natural extracts from Momordica charantia L. (Cucurbitaceae) used in traditional medicine because of their antimicrobial and biological activities. In this study, we evaluated the extract of M. charantia for its antiepimastigote, antifungal, and cytotoxic activities. An ethanol extract of leaves from M. charantia was prepared. To research in vitro antiepimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1 × 10(5) cells/mL in 200 µl tryptose-liver infusion. For the cytotoxicity assay, J774 macrophages were used. The antifungal activity was evaluated by microdilution using strains of Candida albicans, Candida tropicalis, and Candida krusei. The effective concentration capable of killing 50% of parasites (IC(50)) was 46.06 µg/mL. The minimum inhibitory concentration (MIC) was ≤ 1024 µg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with an extract of M. charantia. Our results indicate that M. charantia could be a source of plant-derived natural products with antiepimastigote and antifungal-modifying activity with moderate toxicity.

Antioxidant properties of the essential oil of Eugenia caryophyllata and its antifungal activity against a large number of clinical Candida species.

PubMed

Chaieb, Kamel; Zmantar, Tarek; Ksouri, Riadh; Hajlaoui, Hafedh; Mahdouani, Kacem; Abdelly, Chedly; Bakhrouf, Amina

2007-09-01

Many essential oils are known to possess an antioxidant activity and antifungal properties and therefore they potentially act as antimycotic agents. Essential oil of clove (Eugenia caryophyllata) was isolated by hydrodistillation. The chemical composition of the essential oil was analysed by gas chromatography and gas chromatography/mass spectroscopy. The antioxidant effect of the tested oil was evaluated by measuring its 2,2-diphenyl-l-1-picrylhydrazil radical scavenging ability and the antiradical dose required to cause a 50% inhibition (IC50) was recorded. The antifungal activity of essential oils was evaluated against 53 human pathogenic yeasts using a disc paper diffusion method. Our results show that the major components present in the clove bund oil were eugenol (88.6%), eugenyl acetate (5.6%), beta-caryophyllene (1.4%) and 2-heptanone (0.9%). The tested essential oil exhibited a very strong radical scavenging activity (IC50 = 0.2 microg ml-1) when compared with the synthetic antioxidant (tert-butylated hydroxytoluene, IC50 = 11.5 microg ml-1). On the other hand, this species displayed an important antifungal effect against the tested strains. It is clear that clove oil shows powerful antifungal activity; and it can be used as an easily accessible source of natural antioxidants and in pharmaceutical applications.

The antifungal pipeline: a reality check

PubMed Central

Perfect, John R.

2017-01-01

Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies — polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) — in the management of these infections has plateaued. Although these drugs are clinically useful, they have several limitations, such as off-target toxicity, and drug-resistant fungi are now emerging. New antifungals are therefore needed. In this Review, I discuss the robust and dynamic antifungal pipeline, including results from preclinical academic efforts through to pharmaceutical industry products, and describe the targets, strategies, compounds and potential outcomes. PMID:28496146

Antagonistic Action of Bacillus subtilis Strain SG6 on Fusarium graminearum

PubMed Central

Zhao, Yueju; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhou, Lu; Wang, Yan; Song, Huimin; Tan, Xinxin; Sun, Lichao; Sangare, Lancine; Folly, Yawa Minnie Elodie; Liu, Yang

2014-01-01

Fusarium graminearum causes Fusarium head blight (FHB), a devastating disease that leads to extensive yield and quality loss of wheat and barley. Bacteria isolated from wheat kernels and plant anthers were screened for antagonistic activity against F. graminearum. Based on its in vitro effectiveness, strain SG6 was selected for characterization and identified as Bacillus subtilis. B. subtilis SG6 exhibited a high antifungal effect on the mycelium growth, sporulation and DON production of F. graminearum with the inhibition rate of 87.9%, 95.6% and 100%, respectively. In order to gain insight into biological control effect in situ, we applied B. subtilis SG6 at anthesis through the soft dough stage of kernel development in field test. It was revealed that B. subtilis SG6 significantly reduced disease incidence (DI), FHB index and DON (P≤0.05). Further, ultrastructural examination shows that B. subtilis SG6 strain induced stripping of F. graminearum hyphal surface by destroying the cellular structure. When hypha cell wall was damaged, the organelles and cytoplasm inside cell would exude, leading to cell death. The antifungal activity of SG6 could be associated with the coproduction of chitinase, fengycins and surfactins. PMID:24651513

Antagonistic action of Bacillus subtilis strain SG6 on Fusarium graminearum.

PubMed

Zhao, Yueju; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhou, Lu; Wang, Yan; Song, Huimin; Tan, Xinxin; Sun, Lichao; Sangare, Lancine; Folly, Yawa Minnie Elodie; Liu, Yang

2014-01-01

Fusarium graminearum causes Fusarium head blight (FHB), a devastating disease that leads to extensive yield and quality loss of wheat and barley. Bacteria isolated from wheat kernels and plant anthers were screened for antagonistic activity against F. graminearum. Based on its in vitro effectiveness, strain SG6 was selected for characterization and identified as Bacillus subtilis. B. subtilis SG6 exhibited a high antifungal effect on the mycelium growth, sporulation and DON production of F. graminearum with the inhibition rate of 87.9%, 95.6% and 100%, respectively. In order to gain insight into biological control effect in situ, we applied B. subtilis SG6 at anthesis through the soft dough stage of kernel development in field test. It was revealed that B. subtilis SG6 significantly reduced disease incidence (DI), FHB index and DON (P ≤ 0.05). Further, ultrastructural examination shows that B. subtilis SG6 strain induced stripping of F. graminearum hyphal surface by destroying the cellular structure. When hypha cell wall was damaged, the organelles and cytoplasm inside cell would exude, leading to cell death. The antifungal activity of SG6 could be associated with the coproduction of chitinase, fengycins and surfactins.

Hybrid genome assembly and annotation of Paenibacillus pasadenensis strain R16 reveals insights on endophytic life style and antifungal activity

PubMed Central

Passera, Alessandro; Marcolungo, Luca; Brasca, Milena; Quaglino, Fabio; Cantaloni, Chiara; Delledonne, Massimo

2018-01-01

Bacteria of the Paenibacillus genus are becoming important in many fields of science, including agriculture, for their positive effects on the health of plants. However, there are little information available on this genus compared to other bacteria (such as Bacillus or Pseudomonas), especially when considering genomic information. Sequencing the genomes of plant-beneficial bacteria is a crucial step to identify the genetic elements underlying the adaptation to life inside a plant host and, in particular, which of these features determine the differences between a helpful microorganism and a pathogenic one. In this study, we have characterized the genome of Paenibacillus pasadenensis, strain R16, recently investigated for its antifungal activities and plant-associated features. An hybrid assembly approach was used integrating the very precise reads obtained by Illumina technology and long fragments acquired with Oxford Nanopore Technology (ONT) sequencing. De novo genome assembly based solely on Illumina reads generated a relatively fragmented assembly of 5.72 Mbp in 99 ungapped sequences with an N50 length of 544 Kbp; hybrid assembly, integrating Illumina and ONT reads, improved the assembly quality, generating a genome of 5.75 Mbp, organized in 6 contigs with an N50 length of 3.4 Mbp. Annotation of the latter genome identified 4987 coding sequences, of which 1610 are hypothetical proteins. Enrichment analysis identified pathways of particular interest for the endophyte biology, including the chitin-utilization pathway and the incomplete siderophore pathway which hints at siderophore parasitism. In addition the analysis led to the identification of genes for the production of terpenes, as for example farnesol, that was hypothesized as the main antifungal molecule produced by the strain. The functional analysis on the genome confirmed several plant-associated, plant-growth promotion, and biocontrol traits of strain R16, thus adding insights in the genetic bases of these complex features, and of the Paenibacillus genus in general. PMID:29351296

Antifungal activity, mode of action and anti-biofilm effects of Laurus nobilis Linnaeus essential oil against Candida spp.

PubMed

Peixoto, Larissa Rangel; Rosalen, Pedro Luiz; Ferreira, Gabriela Lacet Silva; Freires, Irlan Almeida; de Carvalho, Fabíola Galbiatti; Castellano, Lúcio Roberto; de Castro, Ricardo Dias

2017-01-01

The present study demonstrated the antifungal potential of the chemically characterized essential oil (EO) of Laurus nobilis L. (bay laurel) against Candida spp. biofilm adhesion and formation, and further established its mode of action on C. albicans. L. nobilis EO was obtained and tested for its minimum inhibitory and fungicidal concentrations (MIC/MFC) against Candida spp., as well as for interaction with cell wall biosynthesis and membrane ionic permeability. Then we evaluated its effects on the adhesion, formation, and reduction of 48hC. albicans biofilms. The EO phytochemical profile was determined by gas chromatography coupled to mass spectrometry (GC/MS). The MIC and MFC values of the EO ranged from (250 to 500) μg/mL. The MIC values increased in the presence of sorbitol (osmotic protector) and ergosterol, which indicates that the EO may affect cell wall biosynthesis and membrane ionic permeability, respectively. At 2 MIC the EO disrupted initial adhesion of C. albicans biofilms (p<0.05) and affected biofilm formation with no difference compared to nystatin (p>0.05). When applied for 1min, every 8h, for 24h and 48h, the EO reduced the amount of C. albicans mature biofilm with no difference in relation to nystatin (p>0.05). The phytochemical analysis identified isoeugenol as the major compound (53.49%) in the sample. L. nobilis EO has antifungal activity probably due to monoterpenes and sesquiterpenes in its composition. This EO may affect cell wall biosynthesis and membrane permeability, and showed deleterious effects against C. albicans biofilms. Copyright © 2016. Published by Elsevier Ltd.

Antifungal activities of selected essential oils against Fusarium oxysporum f. sp. lycopersici 1322, with emphasis on Syzygium aromaticum essential oil.

PubMed

Sharma, Abhishek; Rajendran, Sasireka; Srivastava, Ankit; Sharma, Satyawati; Kundu, Bishwajit

2017-03-01

The antifungal effects of four essential oils viz., clove (Syzygium aromaticum), lemongrass (Cymbopogon citratus), mint (Mentha × piperita) and eucalyptus (Eucalyptus globulus) were evaluated against wilt causing fungus, Fusarium oxysporum f. sp. lycopersici 1322. The inhibitory effect of oils showed dose-dependent activity on the tested fungus. Most active being the clove oil, exhibiting complete inhibition of mycelial growth and spore germination at 125 ppm with IC 50 value of 18.2 and 0.3 ppm, respectively. Essential oils of lemongrass, mint and eucalyptus were inhibitory at relatively higher concentrations. The Minimum inhibitory concentration (MIC) of clove oil was 31.25 ppm by broth microdilution method. Thirty one different compounds of clove oil, constituting approximately ≥99% of the oil, were identified by gas chromatography-mass spectroscopy analysis. The major components were eugenol (75.41%), E-caryophyllene (15.11%), α-humulene (3.78%) and caryophyllene oxide (1.13%). Effect of clove oil on surface morphology of F. oxysporum f. sp. lycopersici 1322 was studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM). SEM observation revealed shrivelled hyphae while AFM observation showed shrunken and disrupted spores in clove oil treated samples. In pots, 5% aqueous emulsion of clove oil controlled F. oxysporum f. sp. lycopersici 1322 infection on tomato plants. This study demonstrated clove oil as potent antifungal agent that could be used as biofungicide for the control of F. oxysporum f. sp. lycopersici in both preventive and therapeutic manner. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sodium chloride inhibits the growth and infective capacity of the amphibian chytrid fungus and increases host survival rates.

PubMed

Stockwell, Michelle Pirrie; Clulow, John; Mahony, Michael Joseph

2012-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0-5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1-4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation.

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

PubMed Central

Stockwell, Michelle Pirrie; Clulow, John; Mahony, Michael Joseph

2012-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation. PMID:22590639

Protective antifungal activity of essential oils extracted from Buddleja perfoliata and Pelargonium graveolens against fungi isolated from stored grains.

PubMed

Juárez, Z N; Bach, H; Sánchez-Arreola, E; Bach, H; Hernández, L R

2016-05-01

The chemical composition and antifungal activity of essential oils extracted from Buddleja perfoliata and Pelargonium graveolens were analysed to assess their efficacy as a potential alternative to synthetic chemical fungicides to protect stored grain. Essential oils were obtained by hydrodistillation, while GC-MS were used to characterize the components of theses oils. The main components identified from the essential oil of B. perfoliata were cubenol, eudesmol, germacrene D-4-ol and cis-verbenol; whereas (-)-aristolene, β-citronellol and geraniol, were identified in P. graveolens. These essential oils were tested against a panel of fungal strains isolated from stored grains. Toxicity of the essential oils was assessed using two models represented by human-derived macrophages and the brine shrimp assay. Moreover, inflammatory response of the oils was assessed by measuring secretion of the pro-inflammatory cytokines IL-6 and TNF-α using a human-derived macrophage cell line. Results show potent antifungal activity against a collection of fungi, with minimal inhibitory concentrations ranging from 0·3 to 50 μg ml(-1) for both plants. A moderated cytotoxicity was observed, but no inflammatory responses. These oils can be used as an alternative for synthetic chemical fungicides used to protect stored grains. Synthetic chemical fungicides are used to protect stored grains, but their broad use raises concerns about effects on the environment and human health. The impact of the present report is that the use of essential oils is an eco-friendly alternative for fungal control in postharvest grains with a low impact to the environment. © 2016 The Society for Applied Microbiology.

An in vitro study of the antifungal activity of Trichoderma virens 7b and a profile of its non-polar antifungal components released against Ganoderma boninense.

PubMed

Angel, Lee Pei Lee; Yusof, Mohd Termizi; Ismail, Intan Safinar; Ping, Bonnie Tay Yen; Mohamed Azni, Intan Nur Ainni; Kamarudin, Norman Hj; Sundram, Shamala

2016-11-01

Ganoderma boninense is the causal agent of a devastating disease affecting oil palm in Southeast Asian countries. Basal stem rot (BSR) disease slowly rots the base of palms, which radically reduces productive lifespan of this lucrative crop. Previous reports have indicated the successful use of Trichoderma as biological control agent (BCA) against G. boninense and isolate T. virens 7b was selected based on its initial screening. This study attempts to decipher the mechanisms responsible for the inhibition of G. boninense by identifying and characterizing the chemical compounds as well as the physical mechanisms by T. virens 7b. Hexane extract of the isolate gave 62.60% ± 6.41 inhibition against G. boninense and observation under scanning electron microscope (SEM) detected severe mycelial deformation of the pathogen at the region of inhibition. Similar mycelia deformation of G. boninense was observed with a fungicide treatment, Benlate ® indicating comparable fungicidal effect by T. virens 7b. Fraction 4 and 5 of hexane active fractions through preparative thin layer chromatography (P-TLC) was identified giving the best inhibition of the pathogen. These fractions comprised of ketones, alcohols, aldehydes, lactones, sesquiterpenes, monoterpenes, sulphides, and free fatty acids profiled through gas chromatography mass spectrometry detector (GC/MSD). A novel antifungal compound discovery of phenylethyl alcohol (PEA) by T. virens 7b is reported through this study. T. virens 7b also proved to be an active siderophore producer through chrome azurol S (CAS) agar assay. The study demonstrated the possible mechanisms involved and responsible in the successful inhibition of G. boninense.

The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the United States: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

PubMed

Andes, David R; Safdar, Nasia; Baddley, John W; Alexander, Barbara; Brumble, Lisa; Freifeld, Allison; Hadley, Susan; Herwaldt, Loreen; Kauffman, Carol; Lyon, G Marshall; Morrison, Vicki; Patterson, Thomas; Perl, Trish; Walker, Randall; Hess, Tim; Chiller, Tom; Pappas, Peter G

2016-12-01

Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited. The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17 000 OTRs. Analyses were undertaken to determine predictors of infection and mortality. A total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra-abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All-cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non-white race and female gender were more commonly associated with non-albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species. These data highlight the common and distinct features of IC in OTRs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antifungal effect of essential oils on southern yellow pine

Treesearch

Vina W. Yang; Carol A. Clausen

2007-01-01

Moisture management remains the most critical factor for controlling mold growth on wood and wood products during storage, construction, and while in service. When moisture management practices fail to adequately control moisture, plant extracts demonstrating antifungal properties may provide protection for these applications. The objective of this study was to...

Thermo-stability, dose effects and shelf-life of antifungal metabolite-containing supernatants produced by Xenorhabdus szentirmai

USDA-ARS?s Scientific Manuscript database

Xenorhabdus spp. produce secondary metabolites that are antifungal to protect nematode-infected cadavers from fungal colonization. In previous work, the concentrated, or cell-free metabolites of X. szentirmaii exhibited high toxicity against various fungal plant pathogens and showed great potential ...

Antifungal activity of Malaysian honey and propolis extracts against pathogens implicated in denture stomatitis

NASA Astrophysics Data System (ADS)

Yusoff, Nik Yusliyana Nik; Mohamad, Suharni; Abdullah, Haswati@Nurhayati; Rahman, Nurhayu Ab

2016-12-01

Malaysian honey and propolis extracts were investigated for their antifungal properties against pathogens implicated in denture stomatitis. Each of the honey and aqueous extracts propolis at net preparation, 1:1 and 1:2 dilutions was evaluated by using agar well diffusion assay and further investigated by minimum inhibitory concentration (MIC) within the range of 500 mg/mL to 62.5 mg/mL against oral fungi. The findings indicated that there was no effect of propolis on Candida spp for both types of propolis based on no inhibition zones was recorded. Meanwhile, for antifungal activity of honey, only honey from Trigona spp has shown activity at net preparation against C. albicans (10.47 ± 0.23 mm), C. tropicalis (12.29 ± 0.23 mm) and C. glabrata (8.69 ± 0.53 mm). For minimum inhibitory concentration, the data indicates that both propolis have shown inhibitory effect at 500 mg/mL. As for honey, Trigona spp was the effective honey that give MIC value at 250 mg/mL against Candida spp. Apis dorsata honey has shown MIC value at 500 mg/mL while Apis mellifera honey had inhibited C.albicans and C.glabrata at 500 mg/mL except for C.tropicalis at 250 mg/mL. It can be concluded that both propolis has shown weaker antifungal activity against oral fungi while only honey produced from Trigona spp had strong antifungal activity compare to other honey against oral fungi implicated in denture stomatitis.

Melanin Protects Paracoccidioides brasiliensis from the Effects of Antimicrobial Photodynamic Inhibition and Antifungal Drugs

PubMed Central

Baltazar, Ludmila Matos; Werneck, Silvia Maria Cordeiro; Soares, Betânia Maria; Ferreira, Marcus Vinicius L.; Souza, Danielle G.; Pinotti, Marcos; Santos, Daniel Assis

2015-01-01

Paracoccidioidomycosis (PCM) is a public health concern in Latin America and South America that when not correctly treated can lead to patient death. In this study, the influence of melanin produced by Paracoccidioides spp. on the effects of treatment with antimicrobial photodynamic inhibition (aPI) and antifungal drugs was evaluated. aPI was performed using toluidine blue (TBO) as a photosensitizer and a 630-nm light-emitting diode (LED) light. The antifungals tested were itraconazole and amphotericin B. We evaluated the effects of each approach, aPI or antifungals, against nonmelanized and melanized yeast cells by performing susceptibility tests and by quantifying oxidative and nitrosative bursts during the experiments. aPI reduced nonmelanized cells by 3.0 log units and melanized cells by 1.3 log units. The results showed that melanization protects the fungal cell, probably by acting as a scavenger of nitric oxide and reactive oxygen species, but not of peroxynitrite. Melanin also increased the MICs of itraconazole and amphotericin B, and the drugs were fungicidal for nonmelanized and fungistatic for melanized yeast cells. Our study shows that melanin production by Paracoccidioides yeast cells serves a protective function during aPI and treatment with itraconazole and amphotericin B. The results suggest that melanin binds to the drugs, changing their antifungal activities, and also acts as a scavenger of reactive oxygen species and nitric oxide, but not of peroxynitrite, indicating that peroxynitrite is the main radical that is responsible for fungal death after aPI. PMID:25896704

Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

PubMed

de Melo, Nadja Rodrigues; Abdrahman, Ahmed; Greig, Carolyn; Mukherjee, Krishnendu; Thornton, Catherine; Ratcliffe, Norman A; Vilcinskas, Andreas; Butt, Tariq M

2013-01-01

Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR) inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella) larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC) and amphotericin B (AMPH). Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

In vitro antifungal activity of terpinen-4-ol, eugenol, carvone, 1,8-cineole (eucalyptol) and thymol against mycotoxigenic plant pathogens.

PubMed

Morcia, C; Malnati, M; Terzi, V

2012-01-01

The aim of this study was to examine the effect of five naturally occurring compounds from essential oils on 10 different species of mycotoxigenic fungi involved in several plant diseases. The antifungal activities of terpinen-4-ol, eugenol, carvone, 1,8-cineole (eucalyptol) and thymol were observed in vitro on Fusarium subglutinans, Fusarium cerealis, Fusarium verticillioides, Fusarium proliferatum, Fusarium oxysporum, Fusarium sporotrichioides, Aspergillus tubingensis, Aspergillus carbonarius, Alternaria alternata and Penicillium sp. The naturally occurring compounds tested showed toxic effects on in vitro mycelium growth of all fungal species but with different level of potency. The results are encouraging for further investigations of in planta antifungal activities of these essential oils components.

Synthesis and antifungal evaluation of PCA amide analogues.

PubMed

Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

2018-04-18

To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

Fengycin produced by Bacillus subtilis 9407 plays a major role in the biocontrol of apple ring rot disease.

PubMed

Fan, Haiyan; Ru, Jinjiang; Zhang, Yuanyuan; Wang, Qi; Li, Yan

2017-06-01

Apple ring rot, caused by Botryosphaeria dothidea, is a serious apple disease in China. Bacillus subtilis 9407 was isolated from healthy apples and showed strong antifungal activity against B. dothidea. To identify the primary antifungal compound of B. subtilis 9407 and determine its role in controlling apple ring rot, a transposon mutant library was constructed using TnYLB-1, and a mutant completely defective in antifungal activity was obtained. The gene inactivated in the antifungal activity mutant had 98.5% similarity to ppsB in B. subtilis subsp. subtilis str. 168, which encodes one of the five synthetases responsible for synthesizing fengycin. A markerless ppsB deletion mutant was constructed. Compared with the wild-type strain, lipopeptide crude extracts from ΔppsB showed almost no inhibition of B. dothidea mycelial growth. Furthermore, fengycin-like lipopeptides (retention factor 0.1-0.2) that exhibited antifungal activity against B. dothidea were observed in the wild-type strain by thin-layer chromatography (TLC)-bioautography analysis, but not in ΔppsB. Semipreparative reverse-phase high performance liquid chromatography (RP-HPLC) detection revealed that ΔppsB lost the ability to synthesize fengycin. These results suggest that ppsB is responsible for synthesizing fengycin and that fengycin is the major antifungal compound produced by B. subtilis 9407 against B. dothidea. Moreover, a biocontrol assay showed that the control efficacy of ΔppsB was reduced by half compared with the wild-type strain, indicating that fengycin plays a major role in controlling apple ring rot disease. This is the first report on the use of a B. subtilis strain as a potential biological control agent to control apple ring rot disease by the production of fengycin. Copyright © 2017 Elsevier GmbH. All rights reserved.

Antifungal potential of Avicennia schaueriana Stapf & Leech. (Acanthaceae) against Cladosporium and Colletotrichum species.

PubMed

Fardin, K M; Young, M C M

2015-07-01

There is significant interest in research to develop plant extracts with fungicidal activities that are less harmful to the environment and human health than synthetic fungicides. This study aimed to evaluate the antifungal activity of the extracts of Avicennia schaueriana against Colletotrichum and Cladosporium species and to identify the compounds responsible for the activity. Leaves and stems of A. schaueriana were extracted with ethanol and partitioned with petroleum ether, chloroform and ethyl acetate. The antifungal activity of such extracts was tested by bioautography against Cladosporium sphaerospermum, Cladosporium cladosporioides and Colletotrichum lagenarium. Ethanolic extracts, petroleum ether and chloroform fractions of stems had the highest antifungal activity with several active bands (Rf = 0·72 and Rf = 0·55). In the agar dilution assay, ethanolic extract, petroleum ether and chloroform fractions of stems were the most efficacious, presenting 85, 62 and 63% growth inhibition of Colletotrichum gloeopsporioides and minimum inhibitory concentration values between 1 and 1·5 mg ml(-1) , respectively. Analysis carried out using gas chromatography coupled to a mass spectrometry of petroleum ether and chloroform fractions allowed the identification of fatty acids methyl esters, lupeol and naphthoquinones such as lapachol, α-lapachone, naphtho[2,3-b]furan-4,9-dione, 2-isopropyl- and avicenol-C. We may infer that the antifungal activity of A. schaueriana is due to the abundance of these compounds. This study shows that Avicennia schaueriana extracts have a high potential for the growth inhibition of Colletotrichum and Cladosporium ssp. and will provide a starting point for discovering new natural products with antifungal activity. Their development is of particular interest to organic production systems where synthetic fungicides cannot be used. © 2015 The Society for Applied Microbiology.

Antifungal effects of citronella oil against Aspergillus niger ATCC 16404.

PubMed

Li, Wen-Ru; Shi, Qing-Shan; Ouyang, You-Sheng; Chen, Yi-Ben; Duan, Shun-Shan

2013-08-01

Essential oils are aromatic oily liquids obtained from some aromatic plant materials. Certain essential oils such as citronella oil contain antifungal activity, but the antifungal effect is still unknown. In this study, we explored the antifungal effect of citronella oil with Aspergillus niger ATCC 16404. The antifungal activity of citronella oil on conidia of A. niger was determined by poisoned food technique, broth dilution method, and disc volatility method. Experimental results indicated that the citronella oil has strong antifungal activity: 0.125 (v/v) and 0.25 % (v/v) citronella oil inhibited the growth of 5 × 10⁵ spore/ml conidia separately for 7 and 28 days while 0.5 % (v/v) citronella oil could completely kill the conidia of 5 × 10⁵ spore/ml. Moreover, the fungicidal kinetic curves revealed that more than 90 % conidia (initial concentration is 5 × 10⁵ spore/ml) were killed in all the treatments with 0.125 to 2 % citronella oil after 24 h. Furthermore, with increase of citronella oil concentration and treatment time, the antifungal activity was increased correspondingly. The 0.5 % (v/v) concentration of citronella oil was a threshold to kill the conidia thoroughly. The surviving conidia treated with 0.5 to 2 % citronella oil decreased by an order of magnitude every day, and no fungus survived after 10 days. With light microscope, scanning electron microscope, and transmission electron microscope, we found that citronella oil could lead to irreversible alteration of the hyphae and conidia. Based on our observation, we hypothesized that the citronella oil destroyed the cell wall of the A. niger hyphae, passed through the cell membrane, penetrated into the cytoplasm, and acted on the main organelles. Subsequently, the hyphae was collapsed and squashed due to large cytoplasm loss, and the organelles were severely destroyed. Similarly, citronella oil could lead to the rupture of hard cell wall and then act on the sporoplasm to kill the conidia. Nevertheless, the citronella oil provides a potential of being a safe and environmentally friendly fungicide in the future.

A nitric oxide-releasing solution as a potential treatment for fungi associated with tinea pedis.

PubMed

Regev-Shoshani, G; Crowe, A; Miller, C C

2013-02-01

To test a nitric oxide-releasing solution (NORS) as a potential antifungal footbath therapy against Trichophyton mentagrophytes and Trichophyton rubrum during the mycelial and conidial phases. NORS (sodium nitrite citric acid) produces nitric oxide verified by gas chromatography and mass spectrometry (GC-MS). Antifungal activity of this solution was tested against mycelia and conidia of T. mentagrophytes and T. rubrum, using 1-20 mmol l(-1) nitrites and 10-30 min exposure times. The direct effect of the gas released from the solution on the viability of those fungi was tested. NORS demonstrated strong antifungal activity and was found to be dose and time dependent. NO and nitrogen dioxide (NO(2) ) were the only gases detected from this reaction and are likely responsible for the antifungal effect. This in vitro research suggests that a single 20-min exposure to NORS could potentially be used as an effective single-dose treatment against fungi that are associated with tinea pedis in both mycelia and spore phase. This study provides the background for developing a user-friendly footbath treatment for Athlete's Foot that will kill both vegetative fungi and its spores. © 2012 The Society for Applied Microbiology.

Therapeutic potential of TDT 067 (terbinafine in Transfersome): a carrier-based dosage form of terbinafine for onychomycosis.

PubMed

Sigurgeirsson, Bárdur; Ghannoum, Mahmoud

2012-10-01

Current topical treatments for onychomycosis are unsatisfactory. New topical agents that offer efficacy without the potential adverse effects of oral antifungal therapy would benefit patients with this condition and encourage a greater treatment rate. Currently available topical therapies are reviewed, and new approaches for enhancing delivery of the established antifungal terbinafine through the nail are summarized. We focus on the use of ultra-deformable lipid vesicles to facilitate delivery of terbinafine to the nail and surrounding tissue. TDT 067 (terbinafine in Transfersome) is the only such therapy in development for onychomycosis, and we review published preclinical and clinical studies on this formulation. TDT 067 offers the use of new technology to deliver an established antifungal, terbinafine. Preclinical data suggest that the Transfersome accelerates entry of terbinafine released from TDT 067 into fungi and potentiates its antifungal effects, resulting in enhanced activity, compared with conventional terbinafine. This translated into high rates of mycological cure and evidence of clinical effect in a study of TDT 067 administered twice daily for 12 weeks in patients with onychomycosis. An ongoing Phase-III trial involving more than 700 patients treated for 48 weeks is investigating the efficacy and safety of TDT 067.

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae.

PubMed

Reis de Sá, Leandro Figueira; Toledo, Fabiano Travanca; de Sousa, Bruno Artur; Gonçalves, Augusto César; Tessis, Ana Claudia; Wendler, Edison P; Comasseto, João V; Dos Santos, Alcindo A; Ferreira-Pereira, Antonio

2014-07-26

Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. The Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. The present study investigated the effects of 13 synthetic compounds on Pdr5p. Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 μM and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 μM. When tested at 100 μM, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans. We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae

PubMed Central

2014-01-01

Background Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. The Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. The present study investigated the effects of 13 synthetic compounds on Pdr5p. Results Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 μM and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 μM. When tested at 100 μM, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans. Conclusions We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals. PMID:25062749

In vitro antifungal susceptibility testing of Scopulariopsis brevicaulis strains using agar diffusion method.

PubMed

Skóra, Magdalena; Macura, Anna B

2011-01-01

The genus Scopulariopsis is a common soil saprotroph and has been isolated from air, organic waste and also from plant, animal and human tissues. Scopulariopsis has mainly been associated in humans with superficial mycoses, but it has also been described as the cause of subcutaneous and invasive infections. The most common aetiological agent of infections in humans is Scopulariopsis brevicaulis. This species has been reported to be resistant in vitro to broad-spectrum antifungal agents available today. The aim of the study was to establish in vitro antifungal susceptibility of 35 S. brevicaulis strains against amphotericin B (AMB), flucytosine (FC), caspofungin (CAS), terbinafine (TER), ciclopirox (CIC), voriconazole (VOR), clotrimazole (CTR), miconazole (MCZ), econazole (ECO), ketoconazole (KET), itraconazole (ITR), and fluconazole (FLU). Antifungal susceptibility tests were evaluated by an agar diffusion method (Neo-Sensitabs, Rosco, Denmark). AMB, FC, CAS, ITR and FLU showed no antifungal activity against S. brevicaulis. TER, CIC, CTR, KET, VOR, ECO, and MCZ revealed inhibitory activity for S. brevicaulis, but it varied for each of the drugs. The best antifungal effect was observed for TER and CIC. All isolates had large inhibition zones for TER and CIC. CTR was also inhibitory for all tested S. brevicaulis isolates, but the diameters of inhibition zones were smaller than for TER and CIC. Nearly 89% isolates showed inhibition zones for KET and the mean diameter of the inhibition zone was comparable to CTR. The least antifungal activity exhibited VQR, ECO and MCZ. Because of the multiresistance of S. brevicaulis, infections due to this species may not respond to particular antifungal treatment and other therapeutic approaches should be considered, e.g., combined therapy and/or surgery.

[Does the sampling locality influence on the antifungal activity of the flavonoids of Marrubium vulgare against Aspergillus niger and Candida albicans?].

PubMed

Bouterfas, K; Mehdadi, Z; Aouad, L; Elaoufi, M M; Khaled, M B; Latreche, A; Benchiha, W

2016-09-01

The study was undertaken to determine the effect of the sampling locality on the antifungal activity of the flavonoids extracted from the leaves of Marrubium vulgare L. against two fungal strains; Aspergillus niger ATCC 16404 and Candida albicans ATCC 10231. The leaves were collected from three different sampling localities belonging northwest Algeria: Tessala mount, M'sila forest and Ain Skhouna. The flavonoid extraction was carried out by using organic solvents with increasing polarity. A phytochemical screening was performed by staining test tubes. The inhibition diameters were measured by solid medium diffusion method. The minimum inhibitory concentrations were determined by dilution method on solid medium. The antifungal activity varied significantly (P<0.001) according to the sampling locality of the leaves, the flavonoid extract and its concentration, and the strain fungal type. The inhibition diameters varied between 8.16 and recorded 37.5mm even recording a total inhibition of fungal growth and often exceed those induced marketed antifungals (Amphotericin, Fluconazole, Terbinafine and econazole nitrate). The minimum inhibitory concentrations (MICs) obtained range between 6.25 and 100μg/mL; experiencing strong antifungal inhibition. The phytochemical screening revealed the existence of certain flavonoids classes such as flavans and flavanols which may be responsible of this remarkable antifungal power. The sampling locality of Marrubium vulgare leaves influenced on the antifungal activity of flavonoids. These have proven very good fungistatic and worth valuing in pharmacology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antifungal effect of phenolic extract of fermented rice bran with Rhizopus oryzae and its potential use in loaf bread shelf life extension.

PubMed

Denardi-Souza, Taiana; Luz, Carlos; Mañes, Jordi; Badiale-Furlong, Eliana; Meca, Giuseppe

2018-03-30

In this study the antifungal potential of a phenolic extract obtained from rice bran fermented with Rhizopus oryzae CECT 7560 and its application in the elaboration of bread was assessed. Eighteen compounds with antifungal potential were identified by LC-ESI-qTOF-MS in the extract: organic acids, gallates and gallotannins, flavonoids, ellagic acid and benzophenone derivatives. The extract was active against strains of Fusarium, Aspergillus and Penicillium, with minimum inhibitory concentration ranging from 390 to 3100 µg mL -1 and minimum fungicidal concentration variable from 780 to 6300 µg mL -1 . The strains that were most sensitive to the phenolic extract were F. graminearum, F. culmorum, F. poae, P. roqueforti, P. expansum and A. niger. The phenolic extract added at 5 and 1 g kg -1 concentrations in the preparation of bread loaves contaminated with P. expansum produced a reduction of 0.6 and 0.7 log CFU g -1 . The bread loaves treated with calcium propionate and 10 g kg -1 of the phenolic extract evidenced an improvement in their shelf lives of 3 days. The phenolic extract assessed in this study could be considered as an alternative for inhibiting toxigenic fungi and as a substitute for synthetic compounds in food preservation. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Lactobacillus plantarum with broad antifungal activity: A promising approach to increase safety and shelf-life of cereal-based products.

PubMed

Russo, Pasquale; Arena, Mattia Pia; Fiocco, Daniela; Capozzi, Vittorio; Drider, Djamel; Spano, Giuseppe

2017-04-17

Cereal-based fermented products are worldwide diffused staple food resources and cereal-based beverages represent a promising innovative field in the food market. Contamination and development of spoilage filamentous fungi can result in loss of cereal-based food products and it is a critical safety concern due to their potential ability to produce mycotoxins. Lactic Acid Bacteria (LAB) have been proposed as green strategy for the control of the moulds in the food industry due to their ability to produce antifungal metabolites. In this work, eighty-eight Lactobacillus plantarum strains were screened for their antifungal activity against Aspergillus niger, Aspergillus flavus, Fusarium culmorum, Penicillium roqueforti, Penicillium expansum, Penicillium chrysogenum, and Cladosporium spp. The overlayed method was used for a preliminary discrimination of the strains as no, mild and strong inhibitors. L. plantarum isolates that displayed broad antifungal spectrum activity were further screened based on the antifungal properties of their cell-free supernatant (CFS). CFSs from L. plantarum UFG 108 and L. plantarum UFG 121, in reason of their antifungal potential, were characterized and analyzed by HPLC. Results indicated that lactic acid was produced at high concentration during the growth phase, suggesting that this metabolic aptitude, associated with the low pH, contributed to explain the highlighted antifungal phenotype. Production of phenyllactic acid was also observed. Finally, a new oat-based beverage was obtained by fermentation with the strongest antifungal strain L. plantarum UFG 121. This product was submitted or not to a thermal stabilization and artificially contaminated with F. culmorum. Samples containing L. plantarum UFG 121 showed the best biopreservative effects, since that no differences were observed in terms of some qualitative features between not or contaminated samples with F. culmorum. Here we demonstrate, for the first time, the suitability of LAB strains for the fermentation and antifungal biopreservation of oat-based products. Copyright © 2016 Elsevier B.V. All rights reserved.

Benefits of antifungal therapy in asthma patients with airway mycosis: A retrospective cohort analysis.

PubMed

Li, Evan; Tsai, Chu-Lin; Maskatia, Zahida K; Kakkar, Ekta; Porter, Paul; Rossen, Roger D; Perusich, Sarah; Knight, John M; Kheradmand, Farrah; Corry, David B

2018-06-01

Fungal airway infection (airway mycosis) is increasingly recognized as a cause of asthma and related disorders. However, prior controlled studies of patients treated with antifungal antibiotics have produced conflicting results. Our objective is to measure the effect of antifungal therapy in moderate to severe adult asthmatics with positive fungal sputum cultures in a single center referral-based academic practice. We retrospectively evaluated 41 patients with asthma and culture-proven airway mycosis treated with either terbinafine, fluconazole, itraconazole, voriconazole, or posaconazole for 4 to >12 weeks together with standard bronchodilator and anti-inflammatory agents. Asthma control (1 = very poorly controlled; 2 = not well controlled; and 3 = well controlled), peak expiratory flow rates (PEFR), serum total IgE, and absolute blood eosinophil counts before and after antifungal therapy were assessed. In comparison, we also studied nine patients with airway mycosis and moderate to severe asthma who received standard therapy but no antifungals. Treatment with azole-based and allylamine antifungals was associated with improved asthma control (mean change in asthma control 1.72-2.25; p = 0.004), increased PEFR (69.4% predicted to 79.3% predicted, p = 0.0011) and markedly reduced serum IgE levels (1,075 kU/L to 463 kU/L, p = 0.0005) and blood eosinophil counts (Mean absolute count 530-275, p = 0.0095). Reduction in symptoms, medication use, and relapse rates decreased as duration of therapy increased. Asthmatics on standard therapy who did not receive antifungals showed no improvement in asthma symptoms or PEFR. Antifungals were usually well tolerated, but discontinuation (12.2%) and relapse (50%) rates were relatively high. Antifungals help control symptoms in a subset of asthmatics with culture-proven airway mycosis. Additional randomized clinical trials are warranted to extend and validate these findings. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Antifungal activity of the pygidial gland secretion of Laemostenus punctatus (Coleoptera: Carabidae) against cave-dwelling micromycetes

NASA Astrophysics Data System (ADS)

Nenadić, Marija; Ljaljević-Grbić, Milica; Stupar, Miloš; Vukojević, Jelena; Ćirić, Ana; Tešević, Vele; Vujisić, Ljubodrag; Todosijević, Marina; Vesović, Nikola; Živković, Nemanja; Ćurčić, Srećko

2017-06-01

The antifungal potential of the pygidial gland secretion of the troglophilic ground beetle Laemostenus punctatus from a cave in Southeastern Serbia against cave-dwelling micromycetes, isolated from the same habitat, has been investigated. Eleven collected samples were analyzed and 32 isolates of cave-dwelling fungi were documented. A total of 14 fungal species were identified as members of the genera Aspergillus, Penicillium, Alternaria, Cladosporium, Rhizopus, Trichoderma, Arthrinium, Aureobasidium, Epicoccum, Talaromyces, and Fusarium. Five isolates were selected for testing the antifungal activity of the pygidial gland secretion: Talaromyces duclauxi, Aspergillus brunneouniseriatus, Penicillium sp., Rhizopus stolonifer, and Trichoderma viride. The microdilution method has been applied to detect minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs). The most sensitive isolate was Penicillium sp., while the other isolates demonstrated a high level of resistance to the tested agent. L. punctatus has developed a special mechanism of producing specific compounds that act synergistically within the secretion mixture, which are responsible for the antifungal action against pathogens from the cave. The results open opportunities for further research in the field of ground beetle defense against pathogens, which could have an important application in human medicine, in addition to the environmental impact, primarily.

Antagonistic Activities of Novel Peptides from Bacillus amyloliquefaciens PT14 against Fusarium solani and Fusarium oxysporum.

PubMed

Kim, Young Gwon; Kang, Hee Kyoung; Kwon, Kee-Deok; Seo, Chang Ho; Lee, Hyang Burm; Park, Yoonkyung

2015-12-09

Bacillus species have recently drawn attention due to their potential use in the biological control of fungal diseases. This paper reports on the antifungal activity of novel peptides isolated from Bacillus amyloliquefaciens PT14. Reverse-phase high-performance liquid chromatography revealed that B. amyloliquefaciens PT14 produces five peptides (PT14-1, -2, -3, -4a, and -4b) that exhibit antifungal activity but are inactive against bacterial strains. In particular, PT14-3 and PT14-4a showed broad-spectrum antifungal activity against Fusarium solani and Fusarium oxysporum. The PT14-4a N-terminal amino acid sequence was identified through Edman degradation, and a BLAST homology analysis showed it not to be identical to any other protein or peptide. PT14-4a displayed strong fungicidal activity with minimal inhibitory concentrations of 3.12 mg/L (F. solani) and 6.25 mg/L (F. oxysporum), inducing severe morphological deformation in the conidia and hyphae. On the other hand, PT14-4a had no detectable hemolytic activity. This suggests PT14-4a has the potential to serve as an antifungal agent in clinical therapeutic and crop-protection applications.

Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity.

PubMed

Ahluwalia, Vivek; Kumar, Jitendra; Rana, Virendra S; Sati, Om P; Walia, S

2015-01-01

This investigation was undertaken to identify the major secondary metabolite, produced by two Trichoderma harzianum strains (T-4 and T-5) with their antifungal activity against phytopathogenic fungi using poison food technique. The ethyl acetate extract was subjected to column chromatography using n-hexane, ethyl acetate and methanol gradually. Chromatographic separation of ethyl acetate extract of T. harzianum (T-4) resulted in the isolation and identification of palmitic acid (1), 1,8-dihydroxy-3-methylanthraquinone (2), 6-pentyl-2H-pyran-2-one (3), 2(5H)-furanone (4), stigmasterol (5) and β-sitosterol (6), while T. harzianum (T-5) gave palmitic acid (1), 1-hydroxy-3-methylanthraquinone (7), δ-decanolactone (8), 6-pentyl-2H-pyran-2-one (3), ergosterol (9), harzianopyridone (10) and 6-methyl-1,3,8-trihydroxyanthraquinone (11) as major metabolites. Among compounds screened for antifungal activity, compound 10 was found to be most active (EC50 35.9-50.2 μg mL(-1)). In conclusion, the present investigation provided significant information about antifungal activity and compounds isolated from two different strains of T. harzianum obtained from two different Himalayan locations.

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

PubMed Central

Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

2014-01-01

Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

Comparison of antifungal activities of Vietnamese citrus essential oils.

PubMed

Van Hung, Pham; Chi, Pham Thi Lan; Phi, Nguyen Thi Lan

2013-03-01

Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries.

Phytochemical and antimicrobial study of an antidiabetic plant: Scoparia dulcis L.

PubMed

Latha, M; Ramkumar, K M; Pari, L; Damodaran, P N; Rajeshkannan, V; Suresh, T

2006-01-01

The antimicrobial and antifungal effects of different concentrations of chloroform/methanol fractions of Scoparia dulcis were investigated. The isolated fractions were tested against different bacteria like Salmonella typhii, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris and fungal strains such as Alternaria macrospora, Candida albicans, Aspergillus niger, and Fusarium oxysporum. The isolated fractions exhibited significant antimicrobial and antifungal activity against all the tested organisms compared with respective reference drugs. The isolated fractions of S. dulcis showed properties like antimicrobial and antifungal activities that will enable researchers in turn to look for application-oriented principles.

Essential oil composition and antifungal activity of Foeniculum vulgare Mill obtained by different distillation conditions.

PubMed

Mimica-Dukić, N; Kujundzić, S; Soković, M; Couladis, M

2003-04-01

The influence of different hydrodistillation conditions was evaluated from the standpoint of essential oil yield, chemical composition and antifungal activity from seeds of Foeniculum vulgare Mill. Three hydrodistillation conditions were considered. The main constituents of the oils were: (E)-anethole (72.27%-74.18%), fenchone (11.32%-16.35%) and methyl chavicol (3.78%-5.29%). The method of distillation significantly effected the essential oil yield and quantitative composition, although the antifungal activity of the oils against some fungi was only slightly altered. Copyright 2003 John Wiley & Sons, Ltd.

Improved efficacy in onychomycosis therapy.

PubMed

Gupta, Aditya K; Paquet, Maryse

2013-01-01

The success rate of onychomycosis treatment is limited by several factors, including the access of the therapeutic agent to the fungal mass, the presence of conidia, and the susceptibility of the different infectious agents to the antifungals. Different strategies used to improve efficacy of the currently available antifungal treatments, their rationale, and the published evidence of their beneficial effects are reviewed. An improved efficacy was demonstrated for some of these strategies, such as combined oral and topical antifungal therapies, whereas most of them lack clear and direct evidence of an increase in therapeutic success. © 2013 Elsevier Inc. All rights reserved.

Atmospheric pressure cold plasma as an antifungal therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Peng; Wu Haiyan; Sun Yi

2011-01-10

A microhollow cathode based, direct-current, atmospheric pressure, He/O{sub 2} (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

Antimicrobial Susceptibility of Tinea Capitis in Children from Egypt.

PubMed

Doss, Reham William; El-Rifaie, Abdel-Aziz; Radi, Nagla; El-Sherif, Aya Yehia

2018-01-01

Dermatophytic fungi of genera Trichophyton and Microsporum are the most important fungal species causing tinea capitis. Choice of treatment for tinea capitis is determined by the species of fungus. The aim of the study was to investigate the most prevalent fungal species causing tinea capitis in children from Egypt and the most useful antifungal agent for treatment. A total of 100 patients diagnosed clinically with tinea capitis were included in the study. Samples were collected and sent to the microbiology and immunology laboratory for sample processing and fungal identification by routine laboratory techniques. A study of antifungal susceptibility to chosen antifungal medications (fluconazole, ketoconazole, clotrimazole, miconazole, amphotericin, caspofungin, itraconazole, terbinafine, and griseofulvin) was done by minimum inhibitory concentration technique. Our analysis revealed that Microsporum canis is the most commonly isolated strain. Amphotericin was the most effective antifungal agent followed by terbinafine. The most sensitive strain to fluconazole and griseofulvin is Microsporum gypseum , while Microsporum audouinii was mostly responsive to terbinafine. Identification and evaluation of the antifungal susceptibility of the pathogenic species in a certain geographic region is important to achieve a good clinical response.

Antifungal activity of peppermint and sweet basil essential oils and their major aroma constituents on some plant pathogenic fungi from the vapor phase.

PubMed

Edris, Amr E; Farrag, Eman S

2003-04-01

The vapors of peppermint oil and two of its major constituents (menthol and menthone), and sweet basil oil and two of its major constituents (linalool and eugenol), were tested against Sclerotinia sclerotiorum (Lib.), Rhizopus stolonifer (Ehrenb. exFr.) Vuill and Mucor sp. (Fisher) in a closed system. These fungi cause deterioration and heavy decay of peach fruit during marketing, shipping and storage. The essential oils, their major individual aroma constituents and blends of the major individual constituents at different ratios inhibited the growth of the fungi in a dose-dependent manner. Menthol was found to be the individual aroma constituent responsible for the antifungal properties of peppermint essential oil, while menthone alone did not show any effect at all doses. In the case of basil oil, linalool alone showed a moderate antifungal activity while eugenol showed no activity at all. Mixing the two components in a ratio similar to their concentrations in the original oil was found to enhance the antifungal properties of basil oil indicating a synergistic effect.

Antifungal Effects of Saponin Extract from Rhizomes of Dioscorea panthaica Prain et Burk against Candida albicans

PubMed Central

Zhuang, Xinming; Feng, Xuechao

2018-01-01

Candida albicans is the most common fungal pathogen causing serious diseases, while there are only a paucity of antifungal drugs. Therefore, the present study was performed to investigate the antifungal effects of saponin extract from rhizomes of Dioscorea panthaica Prain et Burk (Huangshanyao Saponin extract, HSE) against C. albicans. HSE inhibits the planktonic growth and biofilm formation and development of C. albicans. 16–64 μg/mL of HSE could inhibit adhesion to polystyrene surfaces, transition from yeast to filamentous growth, and production of secreted phospholipase and could also induce endogenous reactive oxygen species (ROS) production and disrupt cell membrane in planktonic cells. Inhibitory activities against extracellular exopolysaccharide (EPS) production and ROS production in preformed biofilms could be inhibited by 64–256 μg/mL of HSE. Cytotoxicity against human Chang's liver cells is low, with a half maximal inhibitory concentration (IC50) of about 256 μg/mL. In sum, our study suggested that HSE might be used as a potential antifungal therapeutic against C. albicans. PMID:29853962

Bioactivities of Ketones Terpenes: Antifungal Effect on F. verticillioides and Repellents to Control Insect Fungal Vector, S. zeamais.

PubMed

Pizzolitto, Romina P; Herrera, Jimena M; Zaio, Yesica P; Dambolena, Jose S; Zunino, Maria P; Gallucci, Mauro N; Zygadlo, Julio A

2015-11-12

Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure-activity relationship (Q-SAR) studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87) affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05). The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (-77.8 ± 8.5, p < 0.001) against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize.

Antifungal activity of biogenic tellurium nanoparticles against Candida albicans and its effects on squalene monooxygenase gene expression.

PubMed

Zare, Bijan; Sepehrizadeh, Zargham; Faramarzi, Mohammad Ali; Soltany-Rezaee-Rad, Mohammad; Rezaie, Sassan; Shahverdi, Ahmad Reza

2014-01-01

In this study, we evaluated the antifungal activity of biogenic tellurium nanoparticles (Te NPs) against Candida albicans (ATCC14053). In addition, the effect of these biogenic NPs on squalene monooxygenase activity and the squalene monooxygenase gene (ERG1) expression level was evaluated. Squalene monooxygenase is an important enzyme involved in the synthesis of ergosterol, cholesterol, and phytosterols. Because of the importance of the noted compound, the squalene monooxygenase gene could be considered a good antifungal target. Results showed that biogenic Te NPs had antifungal effect against C. albicans. The minimal fungicidal concentration-minimal inhibitory concentration ratios of the biogenic Te NPs revealed that these NPs exhibited fungicidal effects against the test strain. The results of an enzyme assay using quantitative high-performance liquid chromatography showed squalene accumulation in C. albicans cells because of enzyme inhibition. Real-time PCR analysis showed an increase in the expression of the ERG1 gene in C. albicans cells, which were treated with Te NPs (0.2 mg/mL). It is conclution that Te NPs can inhibit the squalene monooxygenase enzyme, and, as a result, this inhibition phenomenon can cause an increase in the expression level of the ERG1 gene. This is the first report of the anti-Candida effect of biogenic Te NPs and its possible mechanisms. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Effects of a foot bath containing green tea polyphenols on interdigital tinea pedis.

PubMed

Ikeda, Sugako; Kanoya, Yuka; Nagata, Shigeki

2013-01-01

It has been shown that green tea polyphenols (GTP) can directly kill Trichophyton in vitro; however, there are no published clinical studies that show anti-fungal activity of GTP. To identify the effects of GTP on interdigital tinea pedis in elderly patients. Ninety-four patients with interdigital tinea pedis were enrolled and were either given a lukewarm water foot bath containing GTP or placebo treatment. Effects of GTP were assessed based on changes in the size of the affected area, the rate of recurrence, microscopy findings, and overall assessment of skin changes. After 12 weeks of treatment with either GTP or placebo, a significant reduction in the size of the affected area was observed (p<0.001). There were no significant differences between the GTP or placebo groups in the size of the affected area (p=0.638), the recurrence rate (p=0.172), or the microscopy findings (p=1.000). However, the overall assessment demonstrated significant improvements (p=0.010) in the GTP group. These results show that GTP was effective in improving the symptoms of tinea pedis in comparison to only lukewarm water. Our results suggest that GTP could have anti-fungal activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Topical antifungals for seborrhoeic dermatitis

PubMed Central

Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

2015-01-01

Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. Ketoconazole Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%. Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence). Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. Ciclopirox Ciclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungals Clotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies. Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms. Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar. Authors' conclusions Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis. Plain Language Summary Antifungal treatments applied to the skin to treat seborrhoeic dermatitis Background Seborrhoeic dermatitis is a chronic inflammatory skin condition found throughout the world, with rashes with varying degrees of redness, scaling and itching. It affects people of both sexes but is more common among men. The disease usually starts after puberty and can lead to personal discomfort and cosmetic concerns when rashes occur at prominent skin sites. Drugs that act against moulds, also called antifungal agents, have been commonly used on their own or in combination. Review question Do antifungal treatments applied to the skin clear up the rashes and itching of seborrhoeic dermatitis? Study characteristics We included 51 studies with 9052 participants. Trials typically were four weeks long, and very few trials were longer. In all, 24 studies had some involvement of pharmaceutical companies such as funding or employment of the researchers. Key results Particpants taking ketoconazole were 31% less likely than those given placebo to have symptoms that persisted at four weeks of follow-up. This was seen in eight studies with 2520 participants, but wide variation was noted between studies. Ketoconazole was as effective as steroids but had 44% fewer side effects. Without causing more side effects, ciclopirox was 21% more effective than placebo in achieving clinical clearance of rashes. Treatment effect on redness, itching or scaling symptoms of the skin was less clear. Evidence was insufficient to conclude that that one antifungal was superior to other antifungals, but this observation was based on few studies. Ketoconazole and ciclopirox are the most heavily investigated antifungals and are more effective than placebo. Other antifungals might have similar effects, but data are insufficient to underpin this. Common side effects were increased skin redness or itching, burning sensation and hair loss. No studies measured quality of life. Only one study reported on percentage of compliance in different treatment groups. Other studies used surrogates such as acceptability to represent compliance. We therefore could not assess the effect of compliance on treatment outcomes. One study on patients with HIV reported no clear effects of treatments. Quality of the evidence Evidence for the effects of ketoconazole compared with placebo or a steroid was assessed to be of low quality. Evidence derived from comparison of ciclopirox versus placebo was assessed to be of moderate quality. Better quality studies with longer follow-up and better reporting are needed to enlarge the evidence base for antifungals. PMID:25933684

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

PubMed

Lachenmayr, Sarah J; Berking, Sophie; Horns, Heidi; Strobach, Dorothea; Ostermann, Helmut; Berger, Karin

2018-03-25

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified. © 2018 Blackwell Verlag GmbH.

Marine-derived Penicillium in Korea: diversity, enzyme activity, and antifungal properties.

PubMed

Park, Myung Soo; Fong, Jonathan J; Oh, Seung-Yoon; Kwon, Kae Kyoung; Sohn, Jae Hak; Lim, Young Woon

2014-08-01

The diversity of marine-derived Penicillium from Korea was investigated using morphological and multigene phylogenetic approaches, analyzing sequences of the internal transcribed spacer region, β-tubulin gene, and RNA polymerase subunit II gene. In addition, the biological activity of all isolated strains was evaluated. We tested for the extracellular enzyme activity of alginase, endoglucanase, and β-glucosidase, and antifungal activity against two plant pathogens (Colletotrichum acutatum and Fusarium oxysporum). A total of 184 strains of 36 Penicillium species were isolated, with 27 species being identified. The most common species were Penicillium polonicum (19.6 %), P. rubens (11.4 %), P. chrysogenum (11.4 %), and P. crustosum (10.9 %). The diversity of Penicillium strains isolated from soil (foreshore soil and sand) and marine macroorganisms was higher than the diversity of strains isolated from seawater. While many of the isolated strains showed alginase and β-glucosidase activity, no endoglucanase activity was found. More than half the strains (50.5 %) showed antifungal activity against at least one of the plant pathogens tested. Compared with other strains in this study, P. citrinum (strain SFC20140101-M662) showed high antifungal activity against both plant pathogens. The results reported here expand our knowledge of marine-derived Penicillium diversity. The relatively high proportion of strains that showed antifungal and enzyme activity demonstrates that marine-derived Penicillium have great potential to be used in the production of natural bioactive products for pharmaceutical and/or industrial use.

Distribution and Drug Susceptibility of Candida spp. Associated With Female Genital Tract Infection, Chongqing, China

PubMed Central

Luo, Xiaodong; Dong, Xiaojing; Pen, Zhi

2015-01-01

Background Vulvovaginal candidiasis is defined as vulvovaginitis associated with vaginal carriage of Candida spp. and is a common problem with a high rate of morbidity. Objectives To investigate the distribution of Candida spp. and evaluate the corresponding antifungal susceptibility in women with genital tract infection in Chongqing, southwestern China. Patients and Methods Samples (n = 2.129) were obtained from female patients with symptoms of genital tract infection. Candida spp. were isolated from the specimens and were identified using a coloration medium and the VITEK 2 Compact automatic microbial identification system. Antifungal susceptibility testing was performed using the ATB FUNGUS drug susceptibility testing system. Results From 2,129 samples, 478 (22.45%) isolates of Candida were isolated, of which 395 (82.64%) were Candida albicans, 39 (8.16%) were C. glabrata, 21 (4.39%) were C. tropicalis, 9 (1.88%) were C. parapsilosis, and 14 (2.93%) were other Candida spp. The resistance of C. albicans, C. glabrata, and C. tropicalis to 5 antifungal drugs (amphotericin B, voriconazole, fluconazole, 5-fluorocytosine, and itraconazole) ranged from 0.5% to 6.4%, 0% to 7.7%, and 0% to 9.6%, respectively. Conclusions Candida albicans was the major pathogen associated with candidiasis of the female genital tract in patients in Chongqing. The results of the antifungal sensitivity of the isolates suggest that it is important for clinicians to administer appropriate antifungals for the treatment of Candida spp. infections. PMID:28138369

Chemical Composition, Antifungal and Antioxidant Activities of Hedyosmum brasiliense Mart. ex Miq. (Chloranthaceae) Essential Oils

PubMed Central

Murakami, Cynthia; Cordeiro, Inês; Young, Maria Cláudia M.

2017-01-01

Background: Hedyosmum brasiliense Mart. ex Miq. (Chloranthaceae) is a dioecious shrub popularly used in Brazil to treat foot fungi and rheumatism. This work investigated the chemical composition, antifungal, and antioxidant activities of flowers and leaves of H. brasiliense essential oils; Methods: H. brasiliense male and female flowers and leaves were collected at Ilha do Cardoso (São Paulo) and the essential oils were extracted by hydrodistillation and analyzed by GC/MS and their similarity compared by Principal Component Analysis. Antifungal activity was performed by bioautography and antioxidant potential by 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) free radical scavenging and β-carotene/linoleic acid system; Results: The major compounds for all oils were sabinene, curzerene, and carotol, but some differences in their chemical composition were discriminated by Principal Component Analysis (PCA) analysis. Bioautography showed two antifungal bands at Rf’s 0.67 and 0.12 in all samples, the first one was identified as curzerene. The oils presented stronger antioxidant potential in β-carotene/linoleic acid bioassay, with IC50’s from 80 to 180 μg/mL, than in DPPH assay, with IC50’s from 2516.18 to 3783.49 μg/mL; Conclusions: These results suggested that curzerene might be responsible for the antifungal activity of H. brasiliense essential oils. Besides, these essential oils exhibited potential to prevent lipoperoxidation, but they have a weak radical scavenger activity. PMID:28930269

Comparative study on antifungal activities of chitosan nanoparticles and chitosan silver nano composites against Fusarium oxysporum species complex.

PubMed

Dananjaya, S H S; Erandani, W K C U; Kim, Cheol-Hee; Nikapitiya, Chamilani; Lee, Jehee; De Zoysa, Mahanama

2017-12-01

Though the metal nanoparticles (NPs) have been shown favorable results against fungal diseases, erratic environmental toxicity of NPs have raised serious concerns against their applications. Hence, it is vital to modify antifungal compounds into safe substitutes over synthetic chemicals. In this study, antifungal effects of chitosan nanoparticles (CNPs) and chitosan silver nanocomposites (CAgNCs) were compared against Fusarium oxysporum species complex. CNPs and CAgNCs were synthesized, characterized and compared based on the transmission electron microscope, X-ray diffraction, UV-vis absorbance spectra, particle size distribution, zeta potential and thermal stability analysis. Ultra-structural analysis on mycelium membrane of treated F. oxysporum showed that CNPs and CAgNCs could induce a pronounced membrane damage and disruption of the mycelium surface, increase the membrane permeability, and even cell disintegration. CAgNCs showed a significantly higher radial growth inhibition than CNPs in all the tested concentrations. Both CNPs and CAgNCs were not only effective in reducing the fungal growth, but also caused morphological and ultrastructural changes in the pathogen, thereby suggesting its usage as an antifungal dispersion system to control F. oxysporum. Additionally, CNPs and CAgNCs therapy reduced the F. oxysporum infection in zebrafish. Data demonstrates biologically active CNPs and CAgNCs are promising antifungal agents against F. oxysporum. Copyright © 2017 Elsevier B.V. All rights reserved.

Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

PubMed

Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien

2013-09-01

To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

Essential oil of Algerian Eucalyptus citriodora: Chemical composition, antifungal activity.

PubMed

Tolba, H; Moghrani, H; Benelmouffok, A; Kellou, D; Maachi, R

2015-12-01

Essential oil of Eucalyptus citriodora is a natural product which has been attributed for various medicinal uses. In the present investigation, E. citriodora essential oil was used to evaluate its antifungal effect against medically important dermatophytes. Essential oil from the Algerian E. citriodora leaves was analyzed by GC and GC/MS. The antifungal effect of E. citriodora essential oil was evaluated against four dermatophytes: Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum using disc diffusion method, disc volatilization method, and agar dilution method. The chemical composition of the oil revealed the presence of 22 compounds accounting for 95.27% of the oil. The dominant compounds were citronellal (69.77%), citronellol (10.63%) and isopulegol (4.66%). The disc diffusion method, MIC and MFC determination, indicated that E. citriodora essential oil had a higher antifungal potential against the tested strains with inhibition zone diameter which varied from (12 to 90mm) and MIC and MFC values ranged from (0.6 to 5μL/mL and 1.25 to 5μL/mL) respectively. The M. gypseum was the most resistant to the oil. The results of the present study indicated that E. citriodora essential oil may be used as a new antifungal agent recommended by the pharmaceutical industries. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Treatment Outcomes for Malassezia Folliculitis in theDermatology Department of a University Hospital in Japan.

PubMed

Suzuki, Chikako; Hase, Midori; Shimoyama, Harunari; Sei, Yoshihiro

2016-01-01

Topical or systemic antifungal therapy was administered to patients diagnosed with Malassezia folliculitis during the 5-year period between March 2007 and October 2013. The diagnosis of Malassezia folliculitis was established on the basis of characteristic clinical features and direct microscopic findings (10 or more yeast-like fungi per follicle). Treatment consisted of topical application of 2% ketoconazole cream or 100 mg oral itraconazole based on symptom severity and patients' preferences. Treatment was given until papules flattened, and flat papules were examined to determine whether the patient's clinical condition had "improved" and the treatment had been "effective". The subjects were 44 patients (35 men, 9 women), with a mean disease period of 25±15 days. In regard to the lesion site, the frontal portion of the chest was the most common, accounting for 60% of all patients. The mean period required for improvement was 27±16 days in 37 patients receiving the topical antifungal agent and 14±4 days in the 7 patients receiving the systemic antifungal agent. The results were "improved" and the treatment was "effective" in all patients. Neither treatment resulted in any adverse reactions. Although administration of oral agents has been recommended for the treatment of Malassezia folliculitis, this study revealed that beneficial results are safely obtained with topical antifungal therapy alone, similar to those of systemic antifungal agents.

Application of antifungal CFB to increase the durability of cement mortar.

PubMed

Park, Jong-Myong; Park, Sung-Jin; Kim, Wha-Jung; Ghim, Sa-Youl

2012-07-01

Antifungal cement mortar or microbiological calcium carbonate precipitation on cement surface has been investigated as functional concrete research. However, these research concepts have never been fused with each other. In this study, we introduced the antifungal calciteforming bacteria (CFB) Bacillus aryabhattai KNUC205, isolated from an urban tunnel (Daegu, South Korea). The major fungal deteriogens in urban tunnel, Cladosporium sphaerospermum KNUC253, was used as a sensitive fungal strain. B. aryabhattai KNUC205 showed CaCO3 precipitation on B4 medium. Cracked cement mortar pastes were made and neutralized by modified methods. Subsequently, the mixture of B. aryabhattai KNUC205, conidiospore of C. sphaerospermum KNUC253, and B4 agar was applied to cement cracks and incubated at 18 degrees C for 16 days. B. aryabhattai KNUC205 showed fungal growth inhibition against C. sphaerospermum. Furthermore, B. aryabhattai KNUC205 showed crack remediation ability and water permeability reduction of cement mortar pastes. Taken together, these results suggest that the CaCO3 precipitation and antifungal properties of B. aryabhattai KNUC205 could be used as an effective sealing or coating material that can also prevent deteriorative fungal growth. This study is the first application and evaluation research that incorporates calcite formation with antifungal capabilities of microorganisms for an environment-friendly and more effective protection of cement materials. In this research, the conception of microbial construction materials was expanded.

Proanthocyanidins polymeric tannin from Stryphnodendron adstringens are active against Candida albicans biofilms.

PubMed

Luiz, Raul Leal Faria; Vila, Taissa Vieira Machado; de Mello, João Carlos Palazzo; Nakamura, Celso Vataru; Rozental, Sonia; Ishida, Kelly

2015-03-19

Biofilm formation is important in Candida albicans pathogenesis and constitutes a mechanism of antifungal resistance. Thus, we evaluated the effect of proanthocyanidins polymer-rich fractions from Stryphnodendron adstringens (fraction F2 and subfraction F2.4) against C. albicans biofilms. Firstly, the antifungal activity of F2 and F2.4 against planktonic cells of Candida albicans (ATCC 10231) was determined using broth microdilution method. Anti-biofilm effect of F2 and F2.4 was evaluated during biofilm formation or on mature biofilm of C. albicans and compared with standard antifungals amphotericin B and fluconazole. Metabolic activity of sessile and dispersion cells from biofilms after antifungal treatments were measured using a tetrazolium reduction assay and the biofilm total biomass was quantified by crystal violet-based assay. Morphological alterations after treatments were observed using scanning electron microscopy. The anti-biofilm effect of F2 and F2.4 were comparable to standard antifungals (amphotericin B and fluconazole). F2 and F2.4 treatments reduced biofilm metabolic activity (in sessile and in dispersion cells) during biofilm formation, and in mature biofilms, unlike fluconazole, which only prevents the biofilm formation. Treatments with F2, F2.4 or fluconazole reduced biofilm biomass during biofilm formation, but not in mature biofilm. Amphotericin B presented higher inhibitory effect on biofilm formation and on mature biofilm of C. albicans. F2 and F2.4 treatments led to the appearance of dumbbell-shaped blastoconidia and of blastoconidia clusters in biofilms. Proanthocyanidins polymer-rich fractions from S. adstringens successfully inhibited C. albicans planktonic growth and biofilm development, and they represent a potential new agent for the treatment of biofilm-associated candidiasis.

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

PubMed

Santos, Rafael Silva; Loureiro, Kahynna; Rezende, Polyana; Nalone, Luciana; Barbosa, Raquel de Melo; Santini, Antonello; Santos, Ana Cláudia; da Silva, Classius F; Souto, Eliana Barbosa; de Souza, Damião Pergentino; Amaral, Ricardo Guimarães; Severino, Patrícia

2018-06-01

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans.

PubMed

Li, Xiuyun; Yu, Cuixiang; Huang, Xin; Sun, Shujuan

2016-01-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.

In vitro antifungal activity of hydroxychavicol isolated from Piper betle L.

PubMed

Ali, Intzar; Khan, Farrah G; Suri, Krishan A; Gupta, Bishan D; Satti, Naresh K; Dutt, Prabhu; Afrin, Farhat; Qazi, Ghulam N; Khan, Inshad A

2010-02-03

Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of hydroxychavicol were determined by using broth microdilution method following CLSI guidelines. Time kill curve studies, post-antifungal effects and mutation prevention concentrations were determined against Candida species and Aspergillus species "respectively". Hydroxychavicol was also tested for its potential to inhibit and reduce the formation of Candida albicans biofilms. The membrane permeability was measured by the uptake of propidium iodide. Hydroxychavicol exhibited inhibitory effect on fungal species of clinical significance, with the MICs ranging from 15.62 to 500 microg/ml for yeasts, 125 to 500 microg/ml for Aspergillus species, and 7.81 to 62.5 microg/ml for dermatophytes where as the MFCs were found to be similar or two fold greater than the MICs. There was concentration-dependent killing of Candida albicans and Candida glabrata up to 8 x MIC. Hydroxychavicol also exhibited an extended post antifungal effect of 6.25 to 8.70 h at 4 x MIC for Candida species and suppressed the emergence of mutants of the fungal species tested at 2 x to 8 x MIC concentration. Furthermore, it also inhibited the growth of biofilm generated by C. albicans and reduced the preformed biofilms. There was increased uptake of propidium iodide by C. albicans cells when exposed to hydroxychavicol thus indicating that the membrane disruption could be the probable mode of action of hydroxychavicol. The antifungal activity exhibited by this compound warrants its use as an antifungal agent particularly for treating topical infections, as well as gargle mouthwash against oral Candida infections.

In vitro antifungal activity of hydroxychavicol isolated from Piper betle L

PubMed Central

2010-01-01

Background Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies. Methods The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of hydroxychavicol were determined by using broth microdilution method following CLSI guidelines. Time kill curve studies, post-antifungal effects and mutation prevention concentrations were determined against Candida species and Aspergillus species "respectively". Hydroxychavicol was also tested for its potential to inhibit and reduce the formation of Candida albicans biofilms. The membrane permeability was measured by the uptake of propidium iodide. Results Hydroxychavicol exhibited inhibitory effect on fungal species of clinical significance, with the MICs ranging from 15.62 to 500 μg/ml for yeasts, 125 to 500 μg/ml for Aspergillus species, and 7.81 to 62.5 μg/ml for dermatophytes where as the MFCs were found to be similar or two fold greater than the MICs. There was concentration-dependent killing of Candida albicans and Candida glabrata up to 8 × MIC. Hydroxychavicol also exhibited an extended post antifungal effect of 6.25 to 8.70 h at 4 × MIC for Candida species and suppressed the emergence of mutants of the fungal species tested at 2 × to 8 × MIC concentration. Furthermore, it also inhibited the growth of biofilm generated by C. albicans and reduced the preformed biofilms. There was increased uptake of propidium iodide by C. albicans cells when exposed to hydroxychavicol thus indicating that the membrane disruption could be the probable mode of action of hydroxychavicol. Conclusions The antifungal activity exhibited by this compound warrants its use as an antifungal agent particularly for treating topical infections, as well as gargle mouthwash against oral Candida infections. PMID:20128889

Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals.

PubMed

Ku, Tsun Sheng N; Palanisamy, Suresh K A; Lee, Samuel A

2010-11-01

Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans. Based on our finding that high-dose doxycycline exhibited antifungal activity against mature C. albicans biofilms, we evaluated additional antibacterial agents with Gram-positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After screening these antibiotics, it was found that TIG had substantial antifungal activity against mature C. albicans biofilms. Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS). TIG at 2048 μg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128 μg/mL. Against mature biofilms, 2048 μg/mL TIG reduced metabolic activity by 84.2%. Furthermore, addition of 512 μg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms. However, this was not superior to 512 μg/mL TIG alone. TIG at 512 μg/mL increased the antifungal effect of lower concentrations of AmB (0.03125-0.25 μg/mL), but at 0.03125 μg/mL and 0.0625 μg/mL this effect was not superior to 512 μg/mL TIG alone. TIG inhibited the antifungal effect of higher concentrations of AmB (≥ 2 μg/mL). TIG at 512 μg/mL inhibited the antifungal activity of CAS at lower concentrations (0.25-8 μg/mL). These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans. Published by Elsevier B.V.

Antibacterial and antifungal activities of thymol: A brief review of the literature.

PubMed

Marchese, Anna; Orhan, Ilkay Erdogan; Daglia, Maria; Barbieri, Ramona; Di Lorenzo, Arianna; Nabavi, Seyed Fazel; Gortzi, Olga; Izadi, Morteza; Nabavi, Seyed Mohammad

2016-11-01

Thymol (2-isopropyl-5-methylphenol) is the main monoterpene phenol occurring in essential oils isolated from plants belonging to the Lamiaceae family (Thymus, Ocimum, Origanum, and Monarda genera), and other plants such as those belonging to the Verbenaceae, Scrophulariaceae, Ranunculaceae, and Apiaceae families. These essential oils are used in the food industry for their flavouring and preservative properties, in commercial mosquito repellent formulations for their natural repellent effect, in aromatherapy, and in traditional medicine for the treatment of headaches, coughs, and diarrhea. Many different activities of thymol such as antioxidant, anti-inflammatory, local anaesthetic, antinociceptive, cicatrizing, antiseptic, and especially antibacterial and antifungal properties have been shown. This review aims to critically evaluate the available literature regarding the antibacterial and antifungal effects of thymol. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antifungal activity directed toward the Cell wall by 2-cyclohexylidenhydrazo-4-phenyl-thiazole against Candida albicans.

PubMed

de Sa, Nivea Pereira; Possa, Ana Paula; Perez, Pilar; Ferreira, Jaqueline Maria Siqueira; Fonseca, Nayara Cristina; Lino, Cleudiomar Inacio; Cruz, Lana Barreto; de Oliveira, Renata Barbosa; Rosa, Carlos Augusto; Borelli, Beatriz Martins; Mylonakis, Eleftherios; Fuchs, Beth Burgwyn; Johann, Susana

2018-05-30

Background The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. Objectives Investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2-cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. Methods The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. Results CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated the cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. Conclusions In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Combinatorial effect of mutagenesis and medium component optimization on Bacillus amyloliquefaciens antifungal activity and efficacy in eradicating Botrytis cinerea.

PubMed

Masmoudi, Fatma; Ben Khedher, Saoussen; Kamoun, Amel; Zouari, Nabil; Tounsi, Slim; Trigui, Mohamed

2017-04-01

This work is directed towards Bacillus amyloliquefaciens strain BLB371 metabolite production for biocontrol of fungal phytopathogens. In order to maximise antifungal metabolite production by this strain, two approaches were combined: random mutagenesis and medium component optimization. After three rounds of mutagenesis, a hyper active mutant, named M3-7, was obtained. It produces 7 fold more antifungal metabolites (1800AU/mL) than the wild strain in MC medium. A hybrid design was applied to optimise a new medium to enhance antifungal metabolite production by M3-7. The new optimized medium (35g/L of peptone, 32.5g/L of sucrose, 10.5g/L of yeast extract, 2.4g/L of KH 2 PO 4 , 1.3g/L of MgSO 4 and 23mg/L of MnSO 4 ) achieved 1.62 fold enhancement in antifungal compound production (3000AU/mL) by this mutant, compared to that achieved in MC medium. Therefore, combinatory effect of these two approaches (mutagenesis and medium component optimization) allowed 12 fold improvement in antifungal activity (from 250UA/mL to 3000UA/mL). This improvement was confirmed against several phytopathogenic fungi with an increase of MIC and MFC over than 50%. More interestingly, a total eradication of gray mold was obtained on tomato fruits infected by Botrytis cinerea and treated by M3-7, compared to those treated by BLB371. From the practical point of view, combining random mutagenesis and medium optimization could be considered as an excellent tool for obtaining promising biological products useful against phytopathogenic fungi. Copyright © 2017 Elsevier GmbH. All rights reserved.

Copper(II) complexes with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid: Syntheses, crystal structures and antifungal activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Pingping; Li, Jie; Bu, Huaiyu, E-mail: 7213792@qq.com

2014-07-01

Reaction of Cu(II) with an asymmetric semi-rigid organic ligand 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid (HL), yielded five compounds, [Cu{sub 0.5}L]{sub n} (1), [Cu(HL){sub 2}Cl{sub 2}]{sub n} (2), [Cu(HL){sub 2}Cl{sub 2}(H{sub 2}O)] (3), [Cu(L){sub 2}(H{sub 2}O)]{sub n} (4) and [Cu(L)(phen)(HCO{sub 2})]{sub n} (5), which have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. As for compounds 1, 2 and 5, Cu(II) is bridged through HL, Cl{sup -}, and formic acid, respectively, featuring 1D chain-structure. In compound 3, Cu(II) with hexahedral coordination sphere is assembled through hydrogen-bonding into 3D supramolecular framework. In compound 4, 1D chain units –Cu–O–Cu–O–more » are ligand-bridged into a 3D network. All compounds were tested on fungi (Fusarium graminearum, Altemaria solani, Macrophoma kawatsukai, Alternaria alternata and Colletotrichum gloeosporioides). Compound 1 exhibits a better antifungal effect compared to other compounds. An effect of structure on the antifungal activity has also been correlated. - Graphical abstract: Copper(II) compounds with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid, were prepared, structurally characterized and investigated for antifungal activity. - Highlights: • The title compounds formed by thermodynamics and thermokinetics. • The five compounds show higher inhibition percentage than reactants. • The structure effect on the antifungal activity.« less

Antifungal Effect of Malaysian Aloe vera Leaf Extract on Selected Fungal Species of Pathogenic Otomycosis Species in In Vitro Culture Medium.

PubMed

Saniasiaya, Jeyasakthy; Salim, Rosdan; Mohamad, Irfan; Harun, Azian

2017-01-01

Aloe barbadensis miller or Aloe vera has been used for therapeutic purposes since ancient times with antifungal activity known to be amongst its medicinal properties. We conducted a pilot study to determine the antifungal properties of Malaysian Aloe vera leaf extract on otomycosis species including Aspergillus niger and Candida albicans. This laboratory-controlled prospective study was conducted at the Universiti Sains Malaysia. Extracts of Malaysian Aloe vera leaf was prepared in ethanol and solutions via the Soxhlet extraction method. Sabouraud dextrose agar cultured with the two fungal isolates were inoculated with the five different concentrations of each extract (50 g/mL, 25 g/mL, 12.5 g/mL, 6.25 g/mL, and 3.125 g/mL) using the well-diffusion method. Zone of inhibition was measured followed by minimum inhibitory concentration (MIC). For A. niger, a zone of inhibition for alcohol and aqueous extract was seen for all concentrations except 3.125 g/mL. There was no zone of inhibition for both alcohol and aqueous extracts of Aloe vera leaf for C. albicans . The MIC values of aqueous and alcohol extracts were 5.1 g/mL and 4.4 g/mL for A. niger and since no zone of inhibition was obtained for C. albicans the MIC was not determined. The antifungal effect of alcohol extracts of Malaysian Aloe vera leaf is better than the aqueous extract for A. niger ( p < 0.001). Malaysian Aloe vera has a significant antifungal effect towards A. niger.

Molecular Identification, Antifungal Susceptibility Profile, and Biofilm Formation of Clinical and Environmental Rhodotorula Species Isolates

PubMed Central

Nunes, Jorge Meneses; Bizerra, Fernando César; Ferreira, Renata Carmona e

2013-01-01

Rhodotorula species are emergent fungal pathogens capable of causing invasive infections, primarily fungemia. They are particularly problematic in immunosuppressed patients when using a central venous catheter. In this study, we evaluated the species distribution of 51 clinical and 8 environmental Rhodotorula species isolates using the ID32C system and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing and biofilm formation capability using a crystal violet staining assay were performed. Using ITS sequencing as the gold standard, the clinical isolates were identified as follows: 44 R. mucilaginosa isolates, 2 R. glutinis isolates, 2 R. minuta isolates, 2 R. dairenensis isolates, and 1 Rhodosporidium fluviale isolate. The environmental isolates included 7 R. mucilaginosa isolates and 1 R. slooffiae isolate. Using the ID32C system, along with a nitrate assimilation test, only 90.3% of the isolates tested were correctly identified. In the biofilm formation assay, R. mucilaginosa and R. minuta exhibited greater biofilm formation ability compared to the other Rhodotorula species; the clinical isolates of R. mucilaginosa showed greater biofilm formation compared to the environmental isolates (P = 0.04). Amphotericin B showed good in vitro activity (MIC ≤ 1 μg/ml) against planktonic cells, whereas voriconazole and posaconazole showed poor activity (MIC50/MIC90, 2/4 μg/ml). Caspofungin and fluconazole MICs were consistently high for all isolates tested (≥64 μg/ml and ≥ 4 μg/ml, respectively). In this study, we emphasized the importance of molecular methods to correctly identify Rhodotorula species isolates and non-R. mucilaginosa species in particular. The antifungal susceptibility profile reinforces amphotericin B as the antifungal drug of choice for the treatment of Rhodotorula infections. To our knowledge, this is the first study evaluating putative differences in the ability of biofilm formation among different Rhodotorula species. PMID:23114761

Molecular identification, antifungal susceptibility profile, and biofilm formation of clinical and environmental Rhodotorula species isolates.

PubMed

Nunes, Jorge Meneses; Bizerra, Fernando César; Ferreira, Renata Carmona E; Colombo, Arnaldo Lopes

2013-01-01

Rhodotorula species are emergent fungal pathogens capable of causing invasive infections, primarily fungemia. They are particularly problematic in immunosuppressed patients when using a central venous catheter. In this study, we evaluated the species distribution of 51 clinical and 8 environmental Rhodotorula species isolates using the ID32C system and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing and biofilm formation capability using a crystal violet staining assay were performed. Using ITS sequencing as the gold standard, the clinical isolates were identified as follows: 44 R. mucilaginosa isolates, 2 R. glutinis isolates, 2 R. minuta isolates, 2 R. dairenensis isolates, and 1 Rhodosporidium fluviale isolate. The environmental isolates included 7 R. mucilaginosa isolates and 1 R. slooffiae isolate. Using the ID32C system, along with a nitrate assimilation test, only 90.3% of the isolates tested were correctly identified. In the biofilm formation assay, R. mucilaginosa and R. minuta exhibited greater biofilm formation ability compared to the other Rhodotorula species; the clinical isolates of R. mucilaginosa showed greater biofilm formation compared to the environmental isolates (P = 0.04). Amphotericin B showed good in vitro activity (MIC ≤ 1 μg/ml) against planktonic cells, whereas voriconazole and posaconazole showed poor activity (MIC(50)/MIC(90), 2/4 μg/ml). Caspofungin and fluconazole MICs were consistently high for all isolates tested (≥64 μg/ml and ≥ 4 μg/ml, respectively). In this study, we emphasized the importance of molecular methods to correctly identify Rhodotorula species isolates and non-R. mucilaginosa species in particular. The antifungal susceptibility profile reinforces amphotericin B as the antifungal drug of choice for the treatment of Rhodotorula infections. To our knowledge, this is the first study evaluating putative differences in the ability of biofilm formation among different Rhodotorula species.

Genetic and Genomic Architecture of the Evolution of Resistance to Antifungal Drug Combinations

PubMed Central

Hill, Jessica A.; Ammar, Ron; Torti, Dax; Nislow, Corey; Cowen, Leah E.

2013-01-01

The evolution of drug resistance in fungal pathogens compromises the efficacy of the limited number of antifungal drugs. Drug combinations have emerged as a powerful strategy to enhance antifungal efficacy and abrogate drug resistance, but the impact on the evolution of drug resistance remains largely unexplored. Targeting the molecular chaperone Hsp90 or its downstream effector, the protein phosphatase calcineurin, abrogates resistance to the most widely deployed antifungals, the azoles, which inhibit ergosterol biosynthesis. Here, we evolved experimental populations of the model yeast Saccharomyces cerevisiae and the leading human fungal pathogen Candida albicans with azole and an inhibitor of Hsp90, geldanamycin, or calcineurin, FK506. To recapitulate a clinical context where Hsp90 or calcineurin inhibitors could be utilized in combination with azoles to render resistant pathogens responsive to treatment, the evolution experiment was initiated with strains that are resistant to azoles in a manner that depends on Hsp90 and calcineurin. Of the 290 lineages initiated, most went extinct, yet 14 evolved resistance to the drug combination. Drug target mutations that conferred resistance to geldanamycin or FK506 were identified and validated in five evolved lineages. Whole-genome sequencing identified mutations in a gene encoding a transcriptional activator of drug efflux pumps, PDR1, and a gene encoding a transcriptional repressor of ergosterol biosynthesis genes, MOT3, that transformed azole resistance of two lineages from dependent on calcineurin to independent of this regulator. Resistance also arose by mutation that truncated the catalytic subunit of calcineurin, and by mutation in LCB1, encoding a sphingolipid biosynthetic enzyme. Genome analysis revealed extensive aneuploidy in four of the C. albicans lineages. Thus, we identify molecular determinants of the transition of azole resistance from calcineurin dependence to independence and establish multiple mechanisms by which resistance to drug combinations evolves, providing a foundation for predicting and preventing the evolution of drug resistance. PMID:23593013

The Epidemiology and Diagnosis of Invasive Candidiasis Among Premature Infants

PubMed Central

Kelly, Matthew S.; Benjamin, Daniel K.; Smith, P. Brian

2015-01-01

Invasive candidiasis is a leading infectious cause of morbidity and mortality in premature infants. Improved recognition of modifiable risk factors and antifungal prophylaxis have contributed to the recent decline in the incidence of this infection among infants. Invasive candidiasis typically occurs in the first six weeks of life and presents with non-specific signs of sepsis. Definitive diagnosis relies on growth of Candida in blood culture or cultures from other normally sterile sites, but this may identify fewer than half of cases. Improved diagnostics are needed to guide initiation of antifungal therapy in premature infants. PMID:25677999

Eurotium (Aspergillus) repens metabolites and their biological activity.

PubMed

Podojil, M; Sedmera, P; Vokoun, J; Betina, V; Baráthová, H; Duracková, Z; Horáková, K; Nemec, P

1978-01-01

Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mor7 tality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.

Antifungal activity of Leuconostoc citreum and Weissella confusa in rice cakes.

PubMed

Baek, Eunjong; Kim, Hyojin; Choi, Hyejung; Yoon, Sun; Kim, Jeongho

2012-10-01

The antifungal activity of organic acids greatly improves the shelf life of bread and bakery products. However, little is known about the effect of lactic acid fermentation on fungal contamination in rice cakes. Here, we show that lactic acid fermentation in rice dough can greatly retard the growth of three fungal species when present in rice cakes, namely Cladosporium sp. YS1, Neurospora sp. YS3, and Penicillium crustosum YS2. The antifungal activity of the lactic acid bacteria against these fungi was much better than that of 0.3% calcium propionate. We found that organic acids including lactic and acetic acid, which are byproducts of lactic fermentation or can be artificially added, were the main antifungal substances. We also found that some Leuconostoc citreum and Weissella confusa strains could be good starter species for rice dough fermentation. These results imply that these lactic acid bacteria can be applicable to improve the preservation of rice cakes.

In vitro susceptibility of Scedosporium isolates to N-acetyl-L-cysteine alone and in combination with conventional antifungal agents.

PubMed

Homa, Mónika; Galgóczy, László; Tóth, Eszter; Virágh, Máté; Chandrasekaran, Muthusamy; Vágvölgyi, Csaba; Papp, Tamás

2016-10-01

In recent years, Scedosporium species have been more commonly recognized from severe, difficult-to-treat human infections, such as upper respiratory tract and pulmonary infections. To select an appropriate therapeutic approach for these infections is challenging, because of the commonly observed resistance of the causative agents to several antifungal drugs. Therefore, to find a novel strategy for the treatment of pulmonary Scedosporium infections the in vitro antifungal effect of a mucolytic agent, N-acetyl-L-cysteine and its in vitro combinations with conventional antifungals were investigated. Synergistic and indifferent interactions were registered in 23 and 13 cases, respectively. Antagonism was not revealed between the compounds. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antimicrobial and antifungal activities of the extracts and essential oils of Bidens tripartita.

PubMed

Tomczykowa, Monika; Tomczyk, Michał; Jakoniuk, Piotr; Tryniszewska, Elzbieta

2008-01-01

The aim of this study was to determine the antibacterial and antifungal properties of the extracts, subextracts and essential oils of Bidens tripartita flowers and herbs. In the study, twelve extracts and two essential oils were investigated for activity against different Gram-positive Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Gram-negative bacteria Escherichia coli, E. coli (beta-laktamase+), Klebsiella pneumoniae (ESBL+), Pseudomonas aeruginosa and some fungal organisms Candida albicans, C. parapsilosis, Aspergillus fumigatus, A. terreus using a broth microdilution and disc diffusion methods. The results obtained indicate antimicrobial activity of the tested extracts (except butanolic extracts), which however did not inhibit the growth of fungi used in this study. Bacteriostatic effect of both essential oils is insignificant, but they have strong antifungal activity. These results support the use of B. tripartita to treat a microbial infections and it is indicated as an antimicrobial and antifungal agent, which may act as pharmaceuticals and preservatives.

Analysis Of Volatile Fingerprints: A Rapid Screening Method For Antifungal Agents For Efficacy Against Dermatophytes

NASA Astrophysics Data System (ADS)

Naraghi, Kamran; Sahgal, Natasha; Adriaans, Beverley; Barr, Hugh; Magan, Naresh

2009-05-01

The potential of using an electronic nose (E. nose) for rapid screening dermatophytes to antifungal agents was studied. In vitro, the 50 and 90% effective concentration (EC) values of five antifungal agents for T. rubrum and T. mentagrophytes were obtained by mycelial growth assays. Then, the qualitative volatile production patterns of the growth responses of these fungi to these values were incorporated into solid medium were analysed after 96-120 hrs incubation at 25° C using headspace analyses. Overall, results, using PCA and CA demonstrated that it is possible to differentiate between various treatments within 96-120 hrs. This study showed that potential exists for using qualitative volatile patterns as a rapid screening method for antifungal agents for microorganism. This approach could also facilitate the monitoring of antimicrobial drug activities and infection control programmes and perhaps drug resistance build up in microbial species.

Antifungal Effects of Silver Nanoparticles (AgNPs) against Various Plant Pathogenic Fungi.

PubMed

Kim, Sang Woo; Jung, Jin Hee; Lamsal, Kabir; Kim, Yun Seok; Min, Ji Seon; Lee, Youn Su

2012-03-01

This research is concerned with the fungicidal properties of nano-size silver colloidal solution used as an agent for antifungal treatment of various plant pathogens. We used WA-CV-WA13B, WA-AT-WB13R, and WA-PR-WB13R silver nanoparticles (AgNPs) at concentrations of 10, 25, 50, and 100 ppm. Eighteen different plant pathogenic fungi were treated with these AgNPs on potato dextrose agar (PDA), malt extract agar, and corn meal agar plates. We calculated fungal inhibition in order to evaluate the antifungal efficacy of silver nanoparticles against pathogens. The results indicated that AgNPs possess antifungal properties against these plant pathogens at various levels. Treatment with WA-CV-WB13R AgNPs resulted in maximum inhibition of most fungi. Results also showed that the most significant inhibition of plant pathogenic fungi was observed on PDA and 100 ppm of AgNPs.

Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

PubMed Central

Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

2015-01-01

There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

Synthesis and characterization of dithiocarbamate chitosan derivatives with enhanced antifungal activity.

PubMed

Qin, Yukun; Liu, Song; Xing, Ronge; Yu, Huahua; Li, Kecheng; Meng, Xiangtao; Li, Rongfeng; Li, Pengcheng

2012-06-20

In this study, ammonium dithiocarbamate chitosan (ADTCCS) and triethylene diamine dithiocarbamate chitosan (TEDADTCCS) derivatives were obtained respectively by mixing chitosan with carbon disulfide and ammonia (triethylenediamine). Their structures were confirmed by FT-IR, 1H NMR, XRD, DSC, SEM, and elemental analysis. Antifungal properties of them against the plant pathogenic fungi Fusarium oxysporum and Alternaria porri were investigated at concentrations ranged from 31.25 to 500 mg/L. The dithiocarbamate chitosan derivatives had enhanced antifungal activity compared with chitosan. Particularly, they showed obvious inhibitory effect on Fusarium oxysporum. At 500 mg/L, TEDADTCCS inhibited growth of F. oxysporum at 60.4%, stronger than polyoxin and triadimefon whose antifungal indexes were found to be 25.3% and 37.7%. The chitosan derivatives described here deserve further study for use in crop protection. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis

PubMed Central

Saldanha, Camila Arruda; Garcia, Mônica Pereira; Iocca, Diego Cesar; Rebelo, Luciana Guilherme; Souza, Ana Camila Oliveira; Bocca, Anamélia Lorenzetti; Almeida Santos, Maria de Fátima Menezes; Morais, Paulo Cesar; Azevedo, Ricardo Bentes

2016-01-01

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications. PMID:27303789

Phytochemical Composition, Antifungal and Antioxidant Activity of Duguetia furfuracea A. St.-Hill

PubMed Central

Pinho, Francisca Valéria Soares de Araújo; da Cruz, Litiele Cezar; Rodrigues, Nathane Rosa; Waczuk, Emily Pansera; Souza, Celestina Elba Sobral; da Costa, José Galberto Martins; Athayde, Margareth Linde; de Menezes, Irwin Rose Alencar

2016-01-01

Background. Duguetia furfuracea is popular plant used in popular medicine. Hypothesis/Purpose. This claim evaluated the phytochemical composition of the hydroethanolic extract (HEDF), fractions of Duguetia furfuracea, and antioxidant and antifungal activity. Methods. The chemical profile was carried out by HPLC-DAD. The total phenolic contents and flavonoid components were determined by Folin-Ciocalteu and aluminium chloride reaction. The antioxidant activity was measured by scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and ferric reducing ability of plasma (FRAP) methods. The antifungal activity was determined by microdilution assay. Results. HPLC analysis revealed caffeic acid and rutin as major compounds (HEDF), caffeic acid and quercitrin (Mt-OH fraction), and quercitrin and isoquercitrin (Ac-OEt fraction). The highest levels of phenols and total flavonoids were found for Ac-OEt fraction, and the crude extract showed higher in vitro antioxidant potential. The antifungal activity showed synergic effect with fluconazole and EHDF against C. krusei, fluconazole and Mt-OH against C. krusei and C. tropicalis, and Ac-OE and fluconazole against C. albicans. Conclusion. The highest levels of phenols and total flavonoids were marked with antioxidant effect. This is the first report of bioactivity of the synergic effect of HEDF and fractions. More studies would be required to better clarify its mechanism of synergic action. PMID:27127550

Antifungal mechanism of essential oil from Anethum graveolens seeds against Candida albicans.

PubMed

Chen, Yuxin; Zeng, Hong; Tian, Jun; Ban, Xiaoquan; Ma, Bingxin; Wang, Youwei

2013-08-01

This work studied the antifungal mechanism of dill seed essential oil (DSEO) against Candida albicans. Flow cytometric analysis and inhibition of ergosterol synthesis were performed to clarify the mechanism of action of DSEO on C. albicans. Upon treatment of cells with DSEO, propidium iodide penetrated C. albicans through a lesion in its plasma membrane. DSEO also significantly reduced the amount of ergosterol. These findings indicate that the plasma membrane of C. albicans was damaged by DSEO. The effect of DSEO on the functions of the mitochondria in C. albicans was also studied. We assayed the mitochondrial membrane potential (mtΔψ) using rhodamine 123 and determined the production of mitochondrial dysfunction-induced reactive oxygen species (ROS) via flow cytometry. The effects of the antioxidant l-cysteine (Cys) on DSEO-induced ROS production and the antifungal effect of DSEO on C. albicans were investigated. Exposure to DSEO increased mtΔψ. Dysfunctions in the mitochondria caused ROS accumulation in C. albicans. This increase in the level of ROS production and DSEO-induced decrease in cell viability were prevented by the addition of Cys, indicating that ROS are an important mediator of the antifungal action of DSEO. These findings indicate that the cytoplasmic membrane and mitochondria are the main anti-Candida targets of DSEO.

Antifungal activity against Candida albicans of starch Pickering emulsion with thymol or amphotericin B in suspension and calcium alginate films.

PubMed

Cossu, Andrea; Wang, Min S; Chaudhari, Amol; Nitin, Nitin

2015-09-30

Conventional antifungal treatments against Candida albicans in the oral cavity often result in increased cytotoxicity. The goal of this study was to determine the potential of starch Pickering emulsion as a delivery vehicle for an antifungal natural phenolic compound such as thymol in simulated saliva fluid (SSF) compared to amphotericin B. An oil-in-water (o/w) emulsion was stabilized using starch particles. Physical stability of the emulsion and disruption induced by α-amylase activity in SSF was evaluated. Encapsulated thymol in o/w emulsion was compared to encapsulated amphotericin B for antifungal activity against C. albicans in suspension using emulsions or zone inhibition assay on agar plates using emulsions dispersed in alginate films. Results showed that the emulsions were stable for at least three weeks. Digestion of the emulsion by α-amylase led to coalescence of emulsion droplets. The antifungal activity of thymol and amphotericin B in emulsion formulation was enhanced upon incubation with α-amylase. Results from the zone inhibition assay demonstrated efficacy of the emulsions dispersed in alginate films. Interestingly, addition of α-amylase to the alginate films resulted in a decreased inhibitory effect. Overall, this study showed that starch Pickering emulsions have a potential to deliver hydrophobic antifungal compounds to treat oral candidiasis. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis by UPLC-MS-QTOF and antifungal activity of guava (Psidium guajava L.).

PubMed

Bezerra, Camila Fonseca; Rocha, Janaína Esmeraldo; Nascimento Silva, Maria Karollyna do; de Freitas, Thiago Sampaio; de Sousa, Amanda Karine; Dos Santos, Antônia Thassya Lucas; da Cruz, Rafael Pereira; Ferreira, Maciel Horácio; da Silva, Josefa Carolaine Pereira; Machado, Antonio Judson Targino; Carneiro, Joara Nályda Pereira; Sales, Débora Lima; Coutinho, Henrique Douglas Melo; Ribeiro, Paulo Riceli Vasconcelos; de Brito, Edy Sousa; Morais-Braga, Maria Flaviana Bezerra

2018-05-08

Psidium guajava L. is a plant widely used for food and in folk medicine all over the world. Studies have shown that guava leaves have antifungal properties. In this study, Flavonoid and Tannic fractions were tested to investigate their chemical composition and antifungal potential in vitro.21 compounds in the two fractions, presenting a higher content of phenolic compounds. The antifungal assays were performed against Candida albicans, Candida tropicalis and Candida krusei by microdilution to determine the IC 50 and the cell viability curve. Minimal Fungicidal Concentration(MFC) and the inhibitory effects of the association of the fractions with Fluconazole, as well as the assays used to verify any morphological changes were performed in microculture chambers based on the concentrations from the microdilution. The IC 50 of the isolated fractions and the fractions associated with each other were calculated, varying from 69.29 to 3444.62 μg/mL and the fractions associated with fluconazole varied from 925.56 to 1.57 μg/mL, it was clear that the association of the natural product with the antifungal presented a synergism. The fractions affected pleomorphism capacity and have a potential antifungal activity as they caused fungal inhibition in isolated use, potentiated the action of Fluconazole, reducing its concentration and impeding morphological transition, one of the virulence factors of the genus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of sugar and amino acid supplementation on Aureobasidium pullulans NRRL 58536 antifungal activity against four Aspergillus species.

PubMed

Prasongsuk, Sehanat; Ployngam, Saowaluck; Wacharasindhu, Sumrit; Lotrakul, Pongtharin; Punnapayak, Hunsa

2013-09-01

Cultured cell extracts from ten tropical strains of Aureobasidium pullulans were screened for antifungal activity against four pathogenic Aspergillus species (Aspergillus flavus, Aspergillus niger, Aspergillus fumigatus, and Aspergillus terreus) using the well diffusion and conidial germination inhibition assays. The crude cell extract from A. pullulans NRRL 58536 resulted in the greatest fungicidal activity against all four Aspergillus species and so was selected for further investigation into enhancing the production of antifungal activity through optimization of the culture medium, carbon source (sucrose and glucose) and amino acid (phenylalanine, proline, and leucine) supplementation. Sucrose did not support the production of any detectable antifungal activity, while glucose did with the greatest antifungal activity against all four Aspergillus species being produced in cells grown in medium containing 2.5 % (w/v) glucose. With respect to the amino acid supplements, variable trends between the different Aspergillus species and amino acid combinations were observed, with the greatest antifungal activities being obtained when grown with phenylalanine plus leucine supplementation for activity against A. flavus, proline plus leucine for A. terreus, and phenylalanine plus proline and leucine for A. niger and A. fumigatus. Thin layer chromatography, spectrophotometry, high-performance liquid chromatography, (1)H-nuclear magnetic resonance, and MALDI-TOF mass spectrometry analyses were all consistent with the main component of the A. pullulans NRRL 58536 extracts being aureobasidins.

Antifungal mechanism of an antimicrobial peptide, HP (2--20), derived from N-terminus of Helicobacter pylori ribosomal protein L1 against Candida albicans.

PubMed

Lee, Dong Gun; Park, Yoonkyung; Kim, Hee Nam; Kim, Hyung Keun; Kim, Pyoung Il; Choi, Bo Hwa; Hahm, Kyung-Soo

2002-03-08

The antifungal activity and mechanism of HP (2-20), a peptide derived from the N-terminus sequence of Helicobacter pylori Ribosomal Protein L1 were investigated. HP (2--20) displayed a strong antifungal activity against various fungi, and the antifungal activity was inhibited by Ca(2+) and Mg(2+) ions. In order to investigate the antifungal mechanism(s) of HP (2-20), fluorescence activated flow cytometry was performed. As determined by propidium iodide staining, Candida albicans treated with HP (2-20) showed a higher fluorescence intensity than untreated cells and was similar to melittin-treated cells. The effect on fungal cell membranes was examined by investigating the change in membrane dynamics of C. albicans using 1,6-diphenyl-1,3,5-hexatriene as a membrane probe and by testing the membrane disrupting activity using liposome (PC/PS; 3:1, w/w) and by treating protoplasts of C. albicans with the peptide. The action of peptide against fungal cell membrane was further examined by the potassium-release test, and HP (2-20) was able to increase the amount of K(+) released from the cells. The result suggests that HP (2-20) may exert its antifungal activity by disrupting the structure of cell membrane via pore formation or directly interacts with the lipid bilayers in a salt-dependent manner.

Fungal disease and the developing story of bat white-nose syndrome

USGS Publications Warehouse

Blehert, David S.

2012-01-01

Two recently emerged cutaneous fungal diseases of wildlife, bat white-nose syndrome (WNS) and amphibian chytridiomycosis, have devastated affected populations. Fungal diseases are gaining recognition as significant causes of morbidity and mortality to plants, animals, and humans, yet fewer than 10% of fungal species are known. Furthermore, limited antifungal therapeutic drugs are available, antifungal therapeutics often have associated toxicity, and there are no approved antifungal vaccines. The unexpected emergence of WNS, the rapidity with which it has spread, and its unprecedented severity demonstrate both the impacts of novel fungal disease upon naïve host populations and challenges to effective management of such diseases.

Discovery of benzotriazole-azo-phenol/aniline derivatives as antifungal agents.

PubMed

Lv, Min; Ma, Jingchun; Li, Qin; Xu, Hui

2018-01-15

A series of benzotriazole-azo-phenol/aniline derivatives were prepared and evaluated for their antifungal activities against six phytopathogenic fungi such as Fusarium graminearum, Fusarium solani, Alternaria alternate, Valsa mali, Botrytis cinerea, and Curvularia lunata. Among them, compounds IIf, IIn, and IIr showed a broad-spectrum of potent antifungal activities. Especially some compounds displayed 3.5-10.8 folds more potent activities than carbendazim against A. alternata and C. lunata. Notably, compounds IIc, IIm, and IIr exhibited good protective and therapeutic effects against B. cinerea at 200 μg/mL. Their structure-activity relationships were also discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antifungal activity of diketopiperazines and stilbenes against plant pathogenic fungi in vitro.

PubMed

Kumar, S Nishanth; Nambisan, Bala

2014-01-01

The present study aimed to investigate antifungal activity of a stilbene and diketopiperazine compounds against plant pathogenic fungi, including Phytophthora capsici, P. colocasiae, Botrytis cinerea and Colletotrichum gloeosporioides. Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) of stilbenes and diketopiperazines for each fungus were determined using microplate method. Best activity was recorded by stilbenes against P. capsici and P. colocasiae. All four test compounds were effective in inhibiting different stages of the life cycle of test fungi. Stilbenes were more effective than diketopiperazines in inhibiting mycelial growth and inhibiting different stages of the life cycle of P. capsici and P. colocasiae. Rupture of released zoospores induced by stilbenes was reduced by addition of 100 mM glucose. The effects of stilbenes on mycelial growth and zoospore release, but not zoospore rupture, were reduced largely when pH value was above 7. In addition, stilbenes were investigated for its antifungal stability against Phytophthora sp. The results showed that stilbenes maintained strong fungistatic activity over a wide pH range (pH 4–9) and temperature range (70–120 °C). The compound stilbenes exhibited strong and stable broad-spectrum antifungal activity, and had a significant fungicidal effect on fungal cells. Results from prebiocontrol evaluations performed to date are probably useful in the search for alternative approaches to controlling serious plant pathogens.

Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis.

PubMed

Johann, Susana; Sá, Nívea P; Lima, Luciana A R S; Cisalpino, Patricia S; Cota, Betania B; Alves, Tânia M A; Siqueira, Ezequias P; Zani, Carlos L

2010-10-12

The aim of this study was to isolate and identify the antifungal compounds from the extracts of Schinus terebinthifolius (Anacardiaceae) against clinical isolates of the pathogenic fungus Paracoccidioides brasiliensis. The hexane and dichlomethane fractions from leaves and stems of S. terebinthifolius were fractionated using several chromatography techniques to afford four compounds. The compounds isolated from S. terebinthifolius were identified as schinol (1), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (2), quercetin (3), and kaempferol (4). Compounds 1 and 2 were active against different strains of P. brasiliensis, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound 1 with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. terebinthifolius were not able to inhibit cell wall synthesis or assembly using the sorbitol assay. This work reveals for the first time the occurrence of compound 2 and discloses activity of compounds 1 and 2 against several clinical isolates of P. brasiliensis. These results justify further studies to clarify the mechanisms of action of these compounds.

Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans

PubMed Central

Vediyappan, Govindsamy; Dumontet, Vincent; Pelissier, Franck; d’Enfert, Christophe

2013-01-01

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. PMID:24040201

The Effect of Phenazine-1-Carboxylic Acid on Mycelial Growth of Botrytis cinerea Produced by Pseudomonas aeruginosa LV Strain.

PubMed

Simionato, Ane S; Navarro, Miguel O P; de Jesus, Maria L A; Barazetti, André R; da Silva, Caroline S; Simões, Glenda C; Balbi-Peña, Maria I; de Mello, João C P; Panagio, Luciano A; de Almeida, Ricardo S C; Andrade, Galdino; de Oliveira, Admilton G

2017-01-01

One of the most important postharvest plant pathogens that affect strawberries, grapes and tomatoes is Botrytis cinerea , known as gray mold. The fungus remains in latent form until spore germination conditions are good, making infection control difficult, causing great losses in the whole production chain. This study aimed to purify and identify phenazine-1-carboxylic acid (PCA) produced by the Pseudomonas aeruginosa LV strain and to determine its antifungal activity against B. cinerea . The compounds produced were extracted with dichloromethane and passed through a chromatographic process. The purity level of PCA was determined by reversed-phase high-performance liquid chromatography semi-preparative. The structure of PCA was confirmed by nuclear magnetic resonance and electrospray ionization mass spectrometry. Antifungal activity was determined by the dry paper disk and minimum inhibitory concentration (MIC) methods and identified by scanning electron microscopy and confocal microscopy. The results showed that PCA inhibited mycelial growth, where MIC was 25 μg mL -1 . Microscopic analysis revealed a reduction in exopolysaccharide (EPS) formation, showing distorted and damaged hyphae of B. cinerea . The results suggested that PCA has a high potential in the control of B. cinerea and inhibition of EPS (important virulence factor). This natural compound is a potential alternative to postharvest control of gray mold disease.

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

PubMed Central

Houël, Emeline; Gonzalez, German; Bessière, Jean-Marie; Odonne, Guillaume; Eparvier, Véronique; Deharo, Eric; Stien, Didier

2015-01-01

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis. PMID:25742270

Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Khaydarov, R. R.; Khaydarov, R. A.; Estrin, Y.; Evgrafova, S.; Scheper, T.; Endres, C.; Cho, S. Y.

The bactericidal effect of silver nanoparticles obtained by a novel electrochemical method on Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium phoeniceum cultures has been studied. The tests conducted have demonstrated that synthesized silver nanoparticles — when added to water paints or cotton fabrics — show a pronounced antibacterial/antifungal effect. It was shown that smaller silver nanoparticles have a greater antibacterial/antifungal efficacy. The paper also provides a review of scientific literature with regard to recent developments in the field of toxicity of silver nanoparticles and its effect on environment and human health.

Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004-2008.

PubMed

Pfaller, Michael A; Andes, David R; Diekema, Daniel J; Horn, David L; Reboli, Annette C; Rotstein, Coleman; Franks, Billy; Azie, Nkechi E

2014-01-01

This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance) registry from 2004 to 2008. A total of 2,496 patients with non-albicans species of Candida isolates were identified. The identified species were C. glabrata (46.4%), C. parapsilosis (24.7%), C. tropicalis (13.9%), C. krusei (5.5%), C. lusitaniae (1.6%), C. dubliniensis (1.5%) and C. guilliermondii (0.4%); 111 infections involved two or more species of Candida (4.4%). Non-albicans species accounted for more than 50% of all cases of invasive candidiasis in 15 of the 24 sites (62.5%) that contributed more than one case to the survey. Among solid organ transplant recipients, patients with non-transplant surgery, and patients with solid tumors, the most prevalent non-albicans species was C. glabrata at 63.7%, 48.0%, and 53.8%, respectively. In 1,883 patients receiving antifungal therapy on day 3, fluconazole (30.5%) and echinocandins (47.5%) were the most frequently administered monotherapies. Among the 15 reported species, 90-day survival was highest for patients infected with either C. parapsilosis (70.7%) or C. lusitaniae (74.5%) and lowest for patients infected with an unknown species (46.7%) or two or more species (53.2%). In conclusion, this study expands the current knowledge of the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in North America. The variability in species distribution in these centers underscores the importance of local epidemiology in guiding the selection of antifungal therapy.

The Antifungal Plant Defensin HsAFP1 Is a Phosphatidic Acid-Interacting Peptide Inducing Membrane Permeabilization

PubMed Central

Cools, Tanne L.; Vriens, Kim; Struyfs, Caroline; Verbandt, Sara; Ramada, Marcelo H. S.; Brand, Guilherme D.; Bloch, Carlos; Koch, Barbara; Traven, Ana; Drijfhout, Jan W.; Demuyser, Liesbeth; Kucharíková, Soňa; Van Dijck, Patrick; Spasic, Dragana; Lammertyn, Jeroen; Cammue, Bruno P. A.; Thevissen, Karin

2017-01-01

HsAFP1, a plant defensin isolated from coral bells (Heuchera sanguinea), is characterized by broad-spectrum antifungal activity. Previous studies indicated that HsAFP1 binds to specific fungal membrane components, which had hitherto not been identified, and induces mitochondrial dysfunction and cell membrane permeabilization. In this study, we show that HsAFP1 reversibly interacts with the membrane phospholipid phosphatidic acid (PA), which is a precursor for the biosynthesis of other phospholipids, and to a lesser extent with various phosphatidyl inositol phosphates (PtdInsP’s). Moreover, via reverse ELISA assays we identified two basic amino acids in HsAFP1, namely histidine at position 32 and arginine at position 52, as well as the phosphate group in PA as important features enabling this interaction. Using a HsAFP1 variant, lacking both amino acids (HsAFP1[H32A][R52A]), we showed that, as compared to the native peptide, the ability of this variant to bind to PA and PtdInsP’s is reduced (≥74%) and the antifungal activity of the variant is reduced (≥2-fold), highlighting the link between PA/PtdInsP binding and antifungal activity. Using fluorescently labelled HsAFP1 in confocal microscopy and flow cytometry assays, we showed that HsAFP1 accumulates at the cell surface of yeast cells with intact membranes, most notably at the buds and septa. The resulting HsAFP1-induced membrane permeabilization is likely to occur after HsAFP1’s internalization. These data provide novel mechanistic insights in the mode of action of the HsAFP1 plant defensin. PMID:29209301

Xanthones from roots, hairy roots and cell suspension cultures of selected Hypericum species and their antifungal activity against Candida albicans.

PubMed

Zubrická, Daniela; Mišianiková, Anna; Henzelyová, Jana; Valletta, Alessio; De Angelis, Giulia; D'Auria, Felicia Diodata; Simonetti, Giovanna; Pasqua, Gabriella; Čellárová, Eva

2015-11-01

Highest xanthone contents were found in Hypericum pulchrum and H. annulatum untransformed roots. The best anti- Candida activity was obtained for hairy roots extracts of H. tetrapterum clone 2 ATCC 15834. Extracts of root cultures, hairy roots and cell suspensions of selected Hypericum spp. were screened for the presence of xanthones and tested for their antifungal activity against Candida albicans strain ATCC 10231. At least one of the following xanthones, 5-methoxy-2-deprenylrheediaxanthone; 1,3,6,7-tetrahydroxyxanthone; 1,3,5,6-tetrahydroxyxanthone; paxanthone; kielcorin or mangiferin was identified in methanolic extracts of the untransformed root cultures. The highest total xanthone content, with five xanthones, was found in untransformed H. pulchrum and H. annulatum root cultures. Hairy roots and the controls of H. tetrapterum contained 1,7-dihydroxyxanthone, while hairy root cultures and the corresponding controls of H. tomentosum contained toxyloxanthone B, 1,3,6,7- and 1,3,5,6-tetrahydroxyxanthone. Two xanthones, cadensin G and paxanthone, were identified in cell suspension cultures of H. perforatum. Their content increased about two-fold following elicitation with salicylic acid. The anti-Candida activity of the obtained extracts ranged from MIC 64 to >256 µg ml(-1). Among the extracts of Hypericum untransformed roots, the best antifungal activity was obtained for extracts of H. annulatum grown under CD conditions. Extracts of hairy roots clones A4 and 7 ATCC15834 of H. tomentosum and clone 2 ATCC15834 of H. tetrapterum displayed inhibition of 90% of Candida growth with 256 μg ml(-1). Extracts from chitosan-elicitated cells did not show antifungal activity.

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention

PubMed Central

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-01-01

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings. PMID:27429269

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention.

PubMed

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-04-08

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings.

Bioactivities of Ketones Terpenes: Antifungal Effect on F. verticillioides and Repellents to Control Insect Fungal Vector, S. zeamais

PubMed Central

Pizzolitto, Romina P.; Herrera, Jimena M.; Zaio, Yesica P.; Dambolena, Jose S.; Zunino, Maria P.; Gallucci, Mauro N.; Zygadlo, Julio A.

2015-01-01

Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure–activity relationship (Q-SAR) studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87) affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05). The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (−77.8 ± 8.5, p < 0.001) against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize. PMID:27682121

Identification and characterization of a dual-acting antinematodal agent against the pinewood nematode, Bursaphelenchus xylophilus.

PubMed

Oh, Wan-Suk; Jeong, Pan-Young; Joo, Hyoe-Jin; Lee, Jeong-Eui; Moon, Yil-Seong; Cheon, Hyang-Mi; Kim, Jung-Ho; Lee, Yong-Uk; Shim, Yhong-Hee; Paik, Young-Ki

2009-11-11

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca(2+) channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound.

Chemical analysis and toxicity of seaweed extracts with inhibitory activity against tropical fruit anthracnose fungi.

PubMed

Machado, Levi Pompermayer; Matsumoto, Silvia Tamie; Jamal, Claudia Masrouah; da Silva, Marcelo Barreto; Centeno, Danilo da Cruz; Colepicolo Neto, Pio; de Carvalho, Luciana Retz; Yokoya, Nair S

2014-07-01

Banana and papaya are among the most important crops in the tropics, with a value amounting to millions of dollars per year. However, these fruits suffer significant losses due to anthracnose, a fungal disease. It is well known that certain seaweed extracts possess antifungal activity, but no published data appear to exist on the practical application of this property. In the present study, five organic Brazilian seaweed extracts were screened for their activity against banana and papaya anthracnose fungi. Furthermore, cytotoxic and mutagenic effects of the extracts were evaluated by the brine shrimp lethality assay and the Allium cepa root-tip mutagenicity test respectively, while their major components were identified by gas chromatography/mass spectrometry. Strong fungus-inhibitory effects of Ochtodes secundiramea and Laurencia dendroidea extracts were observed on both papaya (100 and 98% respectively) and banana (89 and 78% respectively). This impressive activity could be associated with halogenated terpenes, the major components of both extracts. Only Hypnea musciformis extract showed cytotoxic and mutagenic effects. The results of this study suggest the potential use of seaweed extracts as a source of antifungal agents with low toxicity to control anthracnose in papaya and banana during storage. © 2013 Society of Chemical Industry.

Antagonistic Potential of Native Trichoderma viride Strain against Potent Tea Fungal Pathogens in North East India.

PubMed

Naglot, A; Goswami, S; Rahman, I; Shrimali, D D; Yadav, Kamlesh K; Gupta, Vikas K; Rabha, Aprana Jyoti; Gogoi, H K; Veer, Vijay

2015-09-01

Indigenous strains of Trichoderma species isolated from rhizosphere soils of Tea gardens of Assam, north eastern state of India were assessed for in vitro antagonism against two important tea fungal pathogens namely Pestalotia theae and Fusarium solani. A potent antagonist against both tea pathogenic fungi, designated as SDRLIN1, was selected and identified as Trichoderma viride. The strain also showed substantial antifungal activity against five standard phytopathogenic fungi. Culture filtrate collected from stationary growth phase of the antagonist demonstrated a significantly higher degree of inhibitory activity against all the test fungi, demonstrating the presence of an optimal blend of extracellular antifungal metabolites. Moreover, quantitative enzyme assay of exponential and stationary culture filtrates revealed that the activity of cellulase, β-1,3-glucanase, pectinase, and amylase was highest in the exponential phase, whereas the activity of proteases and chitinase was noted highest in the stationary phase. Morphological changes such as hyphal swelling and distortion were also observed in the fungal pathogen grown on potato dextrose agar containing stationary phase culture filtrate. Moreover, the antifungal activity of the filtrate was significantly reduced but not entirely after heat or proteinase K treatment, demonstrating substantial role of certain unknown thermostable antifungal compound(s) in the inhibitory activity.

An overview of antifungal peptides derived from insect.

PubMed

Faruck, Mohammad Omer; Yusof, Faridah; Chowdhury, Silvia

2016-06-01

Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vitro Antifungal Activity of Burkholderia gladioli pv. agaricicola against Some Phytopathogenic Fungi

PubMed Central

Elshafie, Hazem S.; Camele, Ippolito; Racioppi, Rocco; Scrano, Laura; Iacobellis, Nicola S.; Bufo, Sabino A.

2012-01-01

The trend to search novel microbial natural biocides has recently been increasing in order to avoid the environmental pollution from use of synthetic pesticides. Among these novel natural biocides are the bioactive secondary metabolites of Burkholderia gladioli pv. agaricicola (Bga). The aim of this study is to determine antifungal activity of Bga strains against some phytopathogenic fungi. The fungicidal tests were carried out using cultures and cell-free culture filtrates against Botrytis cinerea, Aspergillus flavus, Aspergillus niger, Penicillium digitatum, Penicillium expansum, Sclerotinia sclerotiorum and Phytophthora cactorum. Results demonstrated that all tested strains exert antifungal activity against all studied fungi by producing diffusible metabolites which are correlated with their ability to produce extracellular hydrolytic enzymes. All strains significantly reduced the growth of studied fungi and the bacterial cells were more bioactive than bacterial filtrates. All tested Bulkholderia strains produced volatile organic compounds (VOCs), which inhibited the fungal growth and reduced the growth rate of Fusarium oxysporum and Rhizoctonia solani. GC/MS analysis of VOCs emitted by strain Bga 11096 indicated the presence of a compound that was identified as 1-methyl-4-(1-methylethenyl)-cyclohexene, a liquid hydrocarbon classified as cyclic terpene. This compound could be responsible for the antifungal activity, which is also in agreement with the work of other authors. PMID:23208371

Antagonistic Potential of Native Trichoderma viride Strain against Potent Tea Fungal Pathogens in North East India

PubMed Central

Naglot, A.; Goswami, S.; Rahman, I.; Shrimali, D. D.; Yadav, Kamlesh K.; Gupta, Vikas K.; Rabha, Aprana Jyoti; Gogoi, H. K.; Veer, Vijay

2015-01-01

Indigenous strains of Trichoderma species isolated from rhizosphere soils of Tea gardens of Assam, north eastern state of India were assessed for in vitro antagonism against two important tea fungal pathogens namely Pestalotia theae and Fusarium solani. A potent antagonist against both tea pathogenic fungi, designated as SDRLIN1, was selected and identified as Trichoderma viride. The strain also showed substantial antifungal activity against five standard phytopathogenic fungi. Culture filtrate collected from stationary growth phase of the antagonist demonstrated a significantly higher degree of inhibitory activity against all the test fungi, demonstrating the presence of an optimal blend of extracellular antifungal metabolites. Moreover, quantitative enzyme assay of exponential and stationary culture filtrates revealed that the activity of cellulase, β-1,3-glucanase, pectinase, and amylase was highest in the exponential phase, whereas the activity of proteases and chitinase was noted highest in the stationary phase. Morphological changes such as hyphal swelling and distortion were also observed in the fungal pathogen grown on potato dextrose agar containing stationary phase culture filtrate. Moreover, the antifungal activity of the filtrate was significantly reduced but not entirely after heat or proteinase K treatment, demonstrating substantial role of certain unknown thermostable antifungal compound(s) in the inhibitory activity. PMID:26361476

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2.

PubMed

Joshua, Ifeoluwapo Matthew; Höfken, Thomas

2017-04-05

Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae . These proteins also control adaptations to anaerobic growth, sterol biosynthesis as well as filamentation and mating. Orthologs of these zinc cluster proteins have been identified in several species of Candida . Upc2 plays a critical role in antifungal resistance in these important human fungal pathogens. Upc2 is therefore an interesting potential target for novel antifungals. In this review we discuss the functions, mode of actions and regulation of Ecm22, Upc2, Sut1 and Sut2 in budding yeast and Candida .

Essential Oils of Myrtaceae Species Growing Wild in Tunisia: Chemical Variability and Antifungal Activity Against Biscogniauxia mediterranea, the Causative Agent of Charcoal Canker.

PubMed

Yangui, Islem; Zouaoui Boutiti, Meriem; Boussaid, Mohamed; Messaoud, Chokri

2017-07-01

The chemical composition of five Eucalyptus species and five Myrtus communis L. populations was investigated using GC/MS and GC-FID. For Eucalyptus essential oils, 32 compounds, representing 88.56 - 96.83% of the total oil according to species, were identified. The main compounds were 1,8-cineole, α-pinene, p-cymene, γ-gurjunene, α-aromadendrene, and β-phellandrene. For Myrtle essential oils, 26 compounds, representing 93.13 - 98.91% of the total oil were identified. α-Pinene, 1,8-cineole, linalool, and myrtenyl acetate were found to be the major compounds. Principal component analysis (PCA) showed chemical differentiation between Eucalyptus species and between Myrtle populations. Biscogniauxia mediterranea, the causative agent of charcoal canker, was identified according to its morphological and molecular characteristics. Essential oils of the investigated Eucalyptus species and Myrtle populations were tested for their antifungal capacity against this fungus. The antifungal activity varied according to the essential oil composition. Biscogniauxia mediterranea exhibited powerful resistance to some essential oils including them of Eucalyptus lehmannii and Eucalyptus sideroxylon but it was very sensitive to Eucalyptus camaldulensis oil (IC 50  = 3.83 mg/ml) and M. communis oil from Zaghouan (IC 50  = 1 mg/ml). This sensitivity was found to be correlated to some essential oil compounds such as p-cymene, carvacrol, cuminaldehyde, and linalool. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation

PubMed Central

Alvarez, Celeste; Andes, David R.; Kang, Jeong Yeon; Krug, Carmen; Kwon, Glen S.

2017-01-01

Purpose Amphotericin B (AmB) and 5-fluorocytosine (5-FC) exhibit additive to synergistic activity against systemic mycoses. Incompatibility of prescribed formulations precludes concomitant IV administration, a route with distinct advantages. Previously, we used PEG-DSPE micelles to produce a reformulation of Fungizone (AmB-SD), AmB solubilized by sodium deoxycholate, called mAmB-90. Herein, we describe a second reformulation that facilitates co-delivery of mAmB-90 and 5-FC, and evaluate the effect of PEG-DSPE micelles on the combination’s activity against Candida albicans. Methods We assessed the effect of 5-FC addition on the stability, in vitro toxicity, and antifungal efficacy of mAmB-90. The aggregation state and particle size of mAmB-90 combined with 5-FC (FmAmB-90) was evaluated over 48 hours. Hemolytic activity was measured in vitro. Antifungal activity was determined in vitro against C. albicans. The efficacy of monotherapy and combination treatment was evaluated in a neutropenic mouse model of disseminated candidiasis. Results The aggregation state, particle size, and hemolytic activity of mAmB-90 were unaffected by 5-FC. While antifungal activity was similar in vitro, mAmB-90 alone and combined with 5-FC was more potent than AmB-SD in vivo. Conclusions Short-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy. PMID:28205003

Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation.

PubMed

Alvarez, Celeste; Andes, David R; Kang, Jeong Yeon; Krug, Carmen; Kwon, Glen S

2017-05-01

Amphotericin B (AmB) and 5-fluorocytosine (5-FC) exhibit additive to synergistic activity against systemic mycoses. Incompatibility of prescribed formulations precludes concomitant IV administration, a route with distinct advantages. Previously, we used PEG-DSPE micelles to produce a reformulation of Fungizone (AmB-SD), AmB solubilized by sodium deoxycholate, called mAmB-90. Herein, we describe a second reformulation that facilitates co-delivery of mAmB-90 and 5-FC, and evaluate the effect of PEG-DSPE micelles on the combination's activity against Candida albicans. We assessed the effect of 5-FC addition on the stability, in vitro toxicity, and antifungal efficacy of mAmB-90. The aggregation state and particle size of mAmB-90 combined with 5-FC (FmAmB-90) was evaluated over 48 h. Hemolytic activity was measured in vitro. Antifungal activity was determined in vitro against C. albicans. The efficacy of monotherapy and combination treatment was evaluated in a neutropenic mouse model of disseminated candidiasis. The aggregation state, particle size, and hemolytic activity of mAmB-90 were unaffected by 5-FC. While antifungal activity was similar in vitro, mAmB-90 alone and combined with 5-FC was more potent than AmB-SD in vivo. Short-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy.

Silver nanoparticles from Pilimelia columellifera subsp. pallida SL19 strain demonstrated antifungal activity against fungi causing superficial mycoses.

PubMed

Wypij, Magdalena; Czarnecka, Joanna; Dahm, Hanna; Rai, Mahendra; Golinska, Patrycja

2017-09-01

In this study, we present the in vitro antifungal activity of silver nanoparticles (AgNPs) synthesized from acidophilic actinobacterium Pilimelia columellifera subsp. pallida SL19 strain, alone and in combination with antibiotics viz., amphotericin B, fluconazole, and ketoconazole against pathogenic fungi, namely Candida albicans, Malassezia furfur, and Trichophyton erinacei. The minimum inhibitory concentration (MIC) and minimum biocidal concentration (MBC) of AgNPs against test fungi were evaluated. The fractional inhibitory concentration (FIC) index was determined to estimate antifungal activity of AgNPs combined with antibiotics. Antifungal activity of AgNPs varied among the tested fungal strains. M. furfur was found to be most sensitive to biogenic silver nanoparticles, followed by C. albicans and T. erinacei. The lowest MIC of AgNPs was noticed against M. furfur (16 μg ml -1 ). Synergistic effect was observed on C. albicans when AgNP were combined with amphotericin B and ketoconazole and on M. furfur with fluconazole and ketoconazole (FIC index of 0.5). Cytotoxic effect of AgNPs on HeLa and 3T3 cell lines was evaluated. The IC 50 values were found to be 55 and 25 μg ml -1 , respectively. The present study indicates that silver nanoparticles from P. columellifera subsp. pallida SL19 strain have antifungal activity, both alone and in combination with antibiotics, and offer a valuable contribution to nanomedicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synergistic and antagonistic effects of immunomodulatory drugs on the action of antifungals against Candida glabrata and Saccharomyces cerevisiae.

PubMed

Tome, Miha; Zupan, Jure; Tomičić, Zorica; Matos, Tadeja; Raspor, Peter

2018-01-01

Candidemia and other forms of invasive fungal infections caused by Candida glabrata and to a lesser extent Saccharomyces cerevisiae are a serious health problem, especially if their steadily rising resistance to the limited range of antifungal drugs is taken into consideration. Various drug combinations are an attractive solution to the resistance problem, and some drug combinations are already common in the clinical environment due to the nature of diseases or therapies. We tested a few of the common antifungal-immunomodulatory drug combinations and evaluated their effect on selected strains of C. glabrata and S. cerevisiae . The combinations were performed using the checkerboard microdilution assay and interpreted using the Loewe additivity model and a model based on the Bliss independence criterion. A synergistic interaction was confirmed between calcineurin inhibitors (Fk506 and cyclosporine A) and antifungals (fluconazole, itraconazole, and amphotericin B). A new antagonistic interaction between mycophenolic acid (MPA) and azole antifungals was discovered in non-resistant strains. A possible mechanism that explains this is induction of the Cdr1 efflux pump by MPA in C. glabrata ATCC 2001. The Pdr1 regulatory cascade plays a role in overall resistance to fluconazole, but it is not essential for the antagonistic interaction. This was confirmed by the Cg pdr1 Δ mutant still displaying the antagonistic interaction between the drugs, although at lower concentrations of fluconazole. This antagonism calls into question the use of simultaneous therapy with MPA and azoles in the clinical environment.

Synthesis, characterization, and antifungal evaluation of novel 1,2,3-triazolium-functionalized starch derivative.

PubMed

Tan, Wenqiang; Zhang, Jingjing; Luan, Fang; Wei, Lijie; Li, Qing; Dong, Fang; Guo, Zhanyong

2017-08-01

1,2,3-Triazolium-functionalized starch derivative was obtained by straightforward quaternization of the synthesized starch derivative bearing 1,2,3-triazole with benzyl bromide by combining the robust attributes of cuprous-catalyzed azide-alkyne cycloaddition. These novel starch derivatives were characterized by FTIR, UV-vis, 1 H NMR, 13 C NMR, and elemental analysis. Their antifungal activities against Colletotrichum lagenarium, Watermelon fusarium, and Phomopsis asparagi were investigated by hypha measurement in vitro. The fungicidal assessment revealed that compared with starch and starch derivative bearing 1,2,3-triazole with inhibitory indices of below 15% at 1.0mg/mL, 1,2,3-triazolium-functionalized starch derivative had superior antifungal activity with inhibitory rates of over 60%. Especially, the best inhibitory index of 1,2,3-triazolium-functionalized starch derivative against Colletotrichum lagenarium attained 90% above at 1.0mg/mL. The results obviously showed that quaternization of 1,2,3-triazole with benzyl bromide could effectively enhance antifungal activity of the synthesized starch derivatives. The synthetic strategy described here could be utilized for the development of starch as novel antifungal biomaterial. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of antifungal activity in essential oil of the Syzygium aromaticum (L.) by extraction, purification and analysis of its main component eugenol

PubMed Central

Rana, Inder Singh; Rana, Aarti Singh; Rajak, Ram Charan

2011-01-01

Antifungal properties of some essential oils have been well documented. Clove oil is reported to have strong antifungal activity against many fungal species. In this study we have evaluated antifungal potential of essential oil of Syzygium aromaticum (L.) against some common fungal pathogens of plants and animals namely, Fusarium moniliforme NCIM 1100, Fusarium oxysporum MTCC 284, Aspergillus sp., Mucor sp., Trichophyton rubrum and Microsporum gypseum. All fungal species were found to be inhibited by the oil when tested through agar well diffusion method. Minimum inhibitory concentration (MIC) was determined for all the species. Column chromatography was performed to separate the eugenol rich fraction from clove oil. Out of seven fractions maximum activity was obtained in column fraction II. TLC and HPLC data confirmed presence of considerable Eugenol in fraction II and clove oil. Microscopic study on effect of clove oil and column fraction II on spores of Mucor sp. and M. gypseum showed distortion and shrinkage while it was absent in other column fractions. So it can be concluded that the antifungal action of clove oil is due to its high eugenol content. PMID:24031751

Antimicrobial Susceptibility of Tinea Capitis in Children from Egypt

PubMed Central

Doss, Reham William; El-Rifaie, Abdel-Aziz; Radi, Nagla; El-Sherif, Aya Yehia

2018-01-01

Background: Dermatophytic fungi of genera Trichophyton and Microsporum are the most important fungal species causing tinea capitis. Choice of treatment for tinea capitis is determined by the species of fungus. Aim: The aim of the study was to investigate the most prevalent fungal species causing tinea capitis in children from Egypt and the most useful antifungal agent for treatment. Patients and Methods: A total of 100 patients diagnosed clinically with tinea capitis were included in the study. Samples were collected and sent to the microbiology and immunology laboratory for sample processing and fungal identification by routine laboratory techniques. A study of antifungal susceptibility to chosen antifungal medications (fluconazole, ketoconazole, clotrimazole, miconazole, amphotericin, caspofungin, itraconazole, terbinafine, and griseofulvin) was done by minimum inhibitory concentration technique. Results: Our analysis revealed that Microsporum canis is the most commonly isolated strain. Amphotericin was the most effective antifungal agent followed by terbinafine. The most sensitive strain to fluconazole and griseofulvin is Microsporum gypseum, while Microsporum audouinii was mostly responsive to terbinafine. Conclusion: Identification and evaluation of the antifungal susceptibility of the pathogenic species in a certain geographic region is important to achieve a good clinical response. PMID:29692458

Evaluation of antifungal activity in essential oil of the Syzygium aromaticum (L.) by extraction, purification and analysis of its main component eugenol.

PubMed

Rana, Inder Singh; Rana, Aarti Singh; Rajak, Ram Charan

2011-10-01

Antifungal properties of some essential oils have been well documented. Clove oil is reported to have strong antifungal activity against many fungal species. In this study we have evaluated antifungal potential of essential oil of Syzygium aromaticum (L.) against some common fungal pathogens of plants and animals namely, Fusarium moniliforme NCIM 1100, Fusarium oxysporum MTCC 284, Aspergillus sp., Mucor sp., Trichophyton rubrum and Microsporum gypseum. All fungal species were found to be inhibited by the oil when tested through agar well diffusion method. Minimum inhibitory concentration (MIC) was determined for all the species. Column chromatography was performed to separate the eugenol rich fraction from clove oil. Out of seven fractions maximum activity was obtained in column fraction II. TLC and HPLC data confirmed presence of considerable Eugenol in fraction II and clove oil. Microscopic study on effect of clove oil and column fraction II on spores of Mucor sp. and M. gypseum showed distortion and shrinkage while it was absent in other column fractions. So it can be concluded that the antifungal action of clove oil is due to its high eugenol content.

Deciphering the mode of action of a mutant Allium sativum Leaf Agglutinin (mASAL), a potent antifungal protein on Rhizoctonia solani.

PubMed

Ghosh, Prithwi; Roy, Amit; Hess, Daniel; Ghosh, Anupama; Das, Sampa

2015-10-26

Mutant Allium sativum leaf agglutinin (mASAL) is a potent, biosafe, antifungal protein that exhibits fungicidal activity against different phytopathogenic fungi, including Rhizoctonia solani. The effect of mASAL on the morphology of R.solani was monitored primarily by scanning electron and light microscopic techniques. Besides different fluorescent probes were used for monitoring various intracellular changes associated with mASAL treatment like change in mitochondrial membrane potential (MMP), intracellular accumulation of reactive oxygen species (ROS) and induction of programmed cell death (PCD). In addition ligand blot followed by LC-MS/MS analyses were performed to detect the putative interactors of mASAL. Knowledge on the mode of function for any new protein is a prerequisite for its biotechnological application. Detailed morphological analysis of mASAL treated R. solani hyphae using different microscopic techniques revealed a detrimental effect of mASAL on both the cell wall and the plasma membrane. Moreover, exposure to mASAL caused the loss of mitochondrial membrane potential (MMP) and the subsequent intracellular accumulation of reactive oxygen species (ROS) in the target organism. In conjunction with this observation, evidence of the induction of programmed cell death (PCD) was also noted in the mASAL treated R. solani hyphae. Furthermore, we investigated its interacting partners from R. solani. Using ligand blots followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses, we identified different binding partners including Actin, HSP70, ATPase and 14-3-3 protein. Taken together, the present study provides insight into the probable mode of action of the antifungal protein, mASAL on R. solani which could be exploited in future biotechnological applications.

The Natural Diyne-Furan Fatty Acid EV-086 Is an Inhibitor of Fungal Delta-9 Fatty Acid Desaturation with Efficacy in a Model of Skin Dermatophytosis

PubMed Central

Diefenbacher, Melanie; Greve, Katrine B. V.; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A.; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A.; Schneiter, Roger; Sorensen, Alexandra S.

2014-01-01

Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids—but not saturated fatty acids—antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086–phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses. PMID:24189258

The natural diyne-furan fatty acid EV-086 is an inhibitor of fungal delta-9 fatty acid desaturation with efficacy in a model of skin dermatophytosis.

PubMed

Knechtle, Philipp; Diefenbacher, Melanie; Greve, Katrine B V; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A; Schneiter, Roger; Sorensen, Alexandra S

2014-01-01

Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids-but not saturated fatty acids-antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086-phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature

PubMed Central

Paolo, William F; Dadachova, Ekaterina; Mandal, Piyali; Casadevall, Arturo; Szaniszlo, Paul J; Nosanchuk, Joshua D

2006-01-01

Background Wangiella dermatitidis is a human pathogenic fungus that is an etiologic agent of phaeohyphomycosis. W. dermatitidis produces a black pigment that has been identified as a dihydroxynaphthalene melanin and the production of this pigment is associated with its virulence. Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis. Results We analyzed the effects of disrupting WdPKS1 on dihydroxynaphthalene melanin production and resistance to antifungal compounds. Transmission electron microscopy revealed that wdpks1Δ-1 yeast had thinner cell walls that lacked an electron-opaque layer compared to wild-type cells. However, digestion of the wdpks1Δ-1 yeast revealed small black particles that were consistent with a melanin-like compound, because they were acid-resistant, reacted with melanin-binding antibody, and demonstrated a free radical signature by electron spin resonance analysis. Despite lacking the WdPKS1 gene, the mutant yeast were capable of catalyzing the formation of melanin from L-3,4-dihyroxyphenylalanine. The wdpks1Δ-1 cells were significantly more susceptible to killing by voriconazole, amphotericin B, NP-1 [a microbicidal peptide], heat and cold, and lysing enzymes than the heavily melanized parental or complemented strains. Conclusion In summary, W. dermatitidis makes WdPKS-dependent and -independent melanins, and the WdPKS1-dependent deposition of melanin in the cell wall confers protection against antifungal agents and environmental stresses. The biological role of the WdPKS-independent melanin remains unclear. PMID:16784529

Análisis de Costo Efectividad de Estrategias de Tratamiento Antimicótico en Pacientes con Neutropenia Febril Persistente y Tratamiento Antibiótico de Amplio Espectro.

PubMed

Gamboa Garay, Oscar Andrés; Fuentes Pachón, Juan Camilo; Cuervo Maldonado, Sonia Isabel; Gómez Rincón, Julio Cesar; Castillo Londoño, Juan Sebastian

2012-12-01

To assess cost-effectiveness of antifungal treatment on patients with persistent fever neutropenia: empiric antifungal therapy (EAT) vs. anticipated antifungal therapy (AAT). A decision model was performed to evaluate the cost-effectiveness of antifungal treatment strategies in patients with febrile neutropenia not responding to a broad spectrum antibiotic treatment. The strategies included were: 1) EAT with amphotericin B deoxycholate; 2) EAT with liposomal amphotericin B; 3) EAT with caspofungin; and 4) AAT with voriconazole and amphotericin B deoxycholate or liposomal amphotericin B or caspofungin in patients who initiate treatment despite having negative CT scan and galactomannan or fail to voriconazole. Effectiveness was measured as the number of deaths averted. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Deterministic and probabilistic sensitivity analyzes were performed. EAT with Amphotericin B deoxycholate was the least expensive and least effective strategy. The EAT with caspofungin was the most effective. The cost per death averted for caspofungin when compared with amphotericin B deoxycholate was $17,011,073.83, which would indicate that this strategy would be cost-effective for the country if the willingness to pay per death averted is equal to or greater than this value. EAT with liposomal amphotericin B and AAT with voriconazole were dominated by AET with caspofungin, which is less costly and more effective. EAT with caspofungin would be cost-effective for Colombia if the threshold per death averted is greater to $18.000.000. If the threshold is lesser the EAT with amphotericin B deoxycholate would be the election. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Hospital resource utilization and costs of inappropriate treatment of candidemia.

PubMed

Arnold, Heather M; Micek, Scott T; Shorr, Andrew F; Zilberberg, Marya D; Labelle, Andrew J; Kothari, Smita; Kollef, Marin H

2010-04-01

To evaluate the impact of inappropriate therapy--defined as delayed antifungal therapy beyond 24 hours from culture collection, inadequate antifungal dosage, or administration of an antifungal to which an isolate was considered resistant--on postculture hospital length of stay and costs, and to evaluate the relationship between modifiable risk factors, including failure to remove a central venous catheter, antifungal delay, and inadequate dosage, for an additive effect on hospital length of stay and costs. Single-center retrospective cohort study. 1250-bed academic medical center. One hundred sixty-seven consecutive adult patients admitted between January 2004 and May 2006 with culture-confirmed Candida bloodstream infections that occurred within 14 days of hospital admission and who received at least one dose of antifungal treatment. Patients were stratified according to appropriateness of antifungal therapy. Appropriate therapy was defined as initiation of an antifungal to which the isolated pathogen was sensitive in vitro within 24 hours of positive culture collection, in addition to receipt of an adequate dose as recommended by the Infectious Diseases Society of America and the antifungal package insert. Postculture length of stay was the primary outcome and hospital costs the secondary outcome. An evaluation of modifiable risk factors was performed separately. Data were analyzed for 167 patients (22 in the appropriate therapy group and 145 in the inappropriate therapy group). Postculture length of stay was shorter in the appropriate therapy group (mean 7 vs 10.4 days, p=0.037). This correlated with total hospital costs that were lower in the appropriate therapy group (mean $15,832 vs $33,021, p<0.001.) A graded increase in costs was noted with increasing number of modifiable risk factors (p=0.001). Inappropriate therapy for Candida bloodstream infection occurring within 14 days of hospitalization was associated with prolonged postculture length of stay and increased costs. A rise in costs, but not length of stay, was noted with increasing modifiable risk factors.

Molecular characterization and antifungal susceptibility of Cryptococcus neoformans strains collected from a single institution in Lima, Peru.

PubMed

Bejar, Vilma; Tello, Mercedes; García, Ruth; Guevara, José M; Gonzales, Sofia; Vergaray, German; Valencia, Esther; Abanto, Enma; Ortega-Loayza, Alex G; Hagen, Ferry; Gutierrez, Ericson L

2015-01-01

Cryptococcosis is a fungal infection with a worldwide distribution, mainly caused by Cryptococcus neoformans and Cryptococcus gattii. To molecularly characterize the mating-types, serotypes, genotypes and antifungal susceptibility profiles of a set of retrospectively isolated C. neoformans strains from Lima, Peru. A set of 32 Cryptococcus spp. strains from the Institute of Tropical Medicine of the National University of San Marcos, Lima, Peru, were included in this retrospective study. Twenty-four strains were isolated from patients, while the remaining 8 were isolated from the environment. Using conventional PCR, 27 (84.4%) of the isolates were identified as C. neoformans var. grubii mating-type alpha and serotype A. Using the AFLP fingerprinting, it was shown that 16 (50%) of the C. neoformans strains were genotype AFLP1, 13 (40.6%) were genotype AFLP1B, 2 (6.3%) were genotype AFLP2, and 1 (3.1%) was found to be a hybrid between both C. neoformans varieties (genotype AFLP3). The antifungal susceptibility profiles for amphotericin B, fluconazole and voriconazole showed that all the 32 C. neoformans are sensitive to these antifungal compounds. In this study we observed that C. neoformans var. grubii (AFLP1 and AFLP1B) and C. neoformans var. neoformans (AFLP2) were the only cryptococcal varieties involved. All strains were found to be sensitive to the antifungals tested, results that are consistent with those found in the international literature. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Evaluation of Antifungal Activity and Mechanism of Action of Citral against Candida albicans.

PubMed

Leite, Maria Clerya Alvino; Bezerra, André Parente de Brito; de Sousa, Janiere Pereira; Guerra, Felipe Queiroga Sarmento; Lima, Edeltrudes de Oliveira

2014-01-01

Candida albicans is a yeast that commensally inhabits the human body and can cause opportunistic or pathogenic infections. Objective. To investigate the antifungal activity of citral against C. albicans. Methodology. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were determined by the broth microdilution techniques. We also investigated possible citral action on cell walls (0.8 M sorbitol), cell membranes (citral to ergosterol binding), the time-kill curve, and biological activity on the yeast's morphology. Results. The MIC and MFC of citral were, respectively, 64 µg/mL and 256 µg/mL. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms of action. In the morphological interference assay, it was observed that the product inhibited pseudohyphae and chlamydoconidia formation. The MIC and the MFC of citral required only 4 hours of exposure to effectively kill 99.9% of the inoculum. Conclusion. Citral showed in vitro antifungal potential against strains of C. albicans. Citral's mechanism of action does not involve the cell wall or ergosterol, and further study is needed to completely describe its effects before being used in the future as a component of new antifungals.

Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana

PubMed Central

Eilenberg, Haviva; Pnini-Cohen, Smadar; Rahamim, Yocheved; Sionov, Edward; Segal, Esther; Carmeli, Shmuel; Zilberstein, Aviah

2010-01-01

Nepenthes spp. are carnivorous plants that have developed insect capturing traps, evolved by specific modification of the leaf tips, and are able to utilize insect degradation products as nutritional precursors. A chitin-induced antifungal ability, based on the production and secretion to the trap liquid of droserone and 5-O-methyldroserone, is described here. Such specific secretion uniquely occurred when chitin injection was used as the eliciting agent and probably reflects a certain kind of defence mechanism that has been evolved for protecting the carnivory-based provision of nutritional precursors. The pitcher liquid containing droserone and 5-O-methyldroserone at 3:1 or 4:1 molar ratio, as well as the purified naphthoquinones, exerted an antifungal effect on a wide range of plant and human fungal pathogens. When tested against Candida and Aspergillus spp., the concentrations required for achieving inhibitory and fungicidal effects were significantly lower than those causing cytotoxicity in cells of the human embryonic kidney cell line, 293T. These naturally secreted 1,4-naphthoquinone derivatives, that are assumed to act via semiquinone enhancement of free radical production, may offer a new lead to develop alternative antifungal drugs with reduced selectable pressure for potentially evolved resistance. PMID:20018905

Botryorhodines A-D, antifungal and cytotoxic depsidones from Botryosphaeria rhodina, an endophyte of the medicinal plant Bidens pilosa.

PubMed

Abdou, Randa; Scherlach, Kirstin; Dahse, Hans-Martin; Sattler, Isabel; Hertweck, Christian

2010-01-01

An endophytic fungus (Botryosphaeria rhodina) was isolated from the stems of the medicinal plant Bidens pilosa (Asteraceae) that is known for its anti-inflammatory, antiseptic and antifungal effects. The ethyl acetate extract of the fungal isolate exhibits significant antifungal activity as well as potent cytotoxic and antiproliferative effects against several cancer cell lines. Activity-guided fractionation resulted in the isolation of a complex of four depsidones, botryorhodines A-D and the auxin indole carboxylic acid. Botryorhodine A and B show moderate to weak cytotoxic activities against HeLa cell lines with a CC(50) of 96.97 microM and 36.41 microM, respectively. In addition, they also show antifungal activity against a range of pathogenic fungi such as Aspergillus terreus (MIC 26.03 microM for botryorhodine A and 49.70 microM for B) and the plant pathogen Fusarium oxysporum (MIC 191.60 microM for botryorhodine A and 238.80 microM for B). A potential role of the endophyte in modulating fungal populations living within or attacking the host plant is discussed. 2009 Elsevier Ltd. All rights reserved.

Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

PubMed

Delarze, Eric; Sanglard, Dominique

2015-11-01

A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alginate Oligosaccharides Inhibit Fungal Cell Growth and Potentiate the Activity of Antifungals against Candida and Aspergillus spp

PubMed Central

Tøndervik, Anne; Sletta, Håvard; Klinkenberg, Geir; Emanuel, Charlotte; Powell, Lydia C.; Pritchard, Manon F.; Khan, Saira; Craine, Kieron M.; Onsøyen, Edvar; Rye, Phil D.; Wright, Chris; Thomas, David W.; Hill, Katja E.

2014-01-01

The oligosaccharide OligoG, an alginate derived from seaweed, has been shown to have anti-bacterial and anti-biofilm properties and potentiates the activity of selected antibiotics against multi-drug resistant bacteria. The ability of OligoG to perturb fungal growth and potentiate conventional antifungal agents was evaluated using a range of pathogenic fungal strains. Candida (n = 11) and Aspergillus (n = 3) spp. were tested using germ tube assays, LIVE/DEAD staining, scanning electron microscopy (SEM), atomic force microscopy (AFM) and high-throughput minimum inhibition concentration assays (MICs). In general, the strains tested showed a significant dose-dependent reduction in cell growth at ≥6% OligoG as measured by optical density (OD600; P<0.05). OligoG (>0.5%) also showed a significant inhibitory effect on hyphal growth in germ tube assays, although strain-dependent variations in efficacy were observed (P<0.05). SEM and AFM both showed that OligoG (≥2%) markedly disrupted fungal biofilm formation, both alone, and in combination with fluconazole. Cell surface roughness was also significantly increased by the combination treatment (P<0.001). High-throughput robotic MIC screening demonstrated the potentiating effects of OligoG (2, 6, 10%) with nystatin, amphotericin B, fluconazole, miconazole, voriconazole or terbinafine with the test strains. Potentiating effects were observed for the Aspergillus strains with all six antifungal agents, with an up to 16-fold (nystatin) reduction in MIC. Similarly, all the Candida spp. showed potentiation with nystatin (up to 16-fold) and fluconazole (up to 8-fold). These findings demonstrate the antifungal properties of OligoG and suggest a potential role in the management of fungal infections and possible reduction of antifungal toxicity. PMID:25409186

Trialkylamine Derivatives Containing a Triazole Moiety as Promising Ergosterol Biosynthesis Inhibitor: Design, Synthesis, and Antifungal Activity.

PubMed

Sui, Guoqing; Zhang, Wen; Zhou, Kun; Li, Yulin; Zhang, Bingyu; Xu, Dan; Zou, Yong; Zhou, Wenming

2017-01-01

As a part of our continuing research on amine derivative antifungal agents, 19 novel target compounds containing 1,2,4-triazole and tertiary amine moieties were designed and synthesized, and their in vitro antifungal activities against six phytopathogenic fungi (Magnaporthe grisea, Alternaria solani, Fusarium solani, Curvularia lunata, A. alternata, F. graminearum) were assayed. All target compounds were elucidated by means of 1 H-NMR, 13 C-NMR, high resolution (HR)-MS, and IR analysis. The results showed that most of the derivatives exhibited obvious activity against each of the fungi at 50 µg/mL. Among them, compounds 7f, l, and o displayed excellent activity against A. solani with median effective concentration values (EC 50 ) of 2.88, 8.20, and 1.92 µg/mL. 7o in particular was superior to tebuconazole (EC 50 =2.03 µg/mL), a commercial fungicide. Furthermore, compounds 7j, k, and m also showed good activity against F. graminearum with EC 50 values of 11.60, 5.14, and 16.24 µg/mL, and the value of 7k was extremely close to that of tebuconazole (EC 50 =3.13 µg/mL). The preliminary analysis of the structure-activity relationship (SAR) demonstrated that combination of the active structure of 1,2,4-triazole with the tertiary amine group containing benzene rings effectively increased the antifungal activities. Generally, introducing halogen atoms obviously improved activities against most of the test fungi to varying degrees, while the presence of OMe decreased the activities. Thus, the results strongly indicate that the newly synthesized derivatives should be lead compounds for the development of novel antifungal agents for the effective control of phytopathogenic fungi.

Combined intrastromal injection of amphotericin B and topical fluconazole in the treatment of resistant cases of keratomycosis: a retrospective study

PubMed Central

Nada, Waled Mahdy; Al Aswad, Mahmoud A; El-Haig, Wael M

2017-01-01

Purpose To evaluate the efficacy of combination therapy of a single intrastromal injection of amphotericin B and topical fluconazole in resistant cases of fungal keratitis, and also topical amphotericin B as monotherapy in terms of the duration of the recovery period and toxic drug effects. Methods This retrospective 2-year study reviewed 68 cases of unilateral fungal keratitis diagnosed by clinical features and positive laboratory culture results. Forty-one cases were resistant and did not respond to monotherapy with an antifungal agent. Thus, they were treated with a single intrastromal injection of amphotericin B in addition to topical fluconazole as combined antifungal therapy, representing group A. Twenty-seven cases were treated with topical amphotericin B as antifungal monotherapy, representing group B. Topical atropine 1% and different antibiotic eye drops were added to the antifungal agents in both groups. Follow-up of patient records was performed monitoring cure rate, duration of recovery period, and toxic drug effects such as pain, burning sensation, and corneal melting. Results The results revealed that group A, treated with combination therapy, showed recovery of 34 cases (82.9%) with a mean duration of 24±6.42 days, significantly different from group B which showed recovery of 16 cases (59.3%) with a mean duration of 39.66±13.6 days. Group A also showed less manifestation of drug toxicity than group B. Conclusion Combined intrastromal injection of amphotericin B and topical fluconazole can provide a good modality in the treatment of resistant cases of fungal keratitis, exhibiting highly potent antifungal effects, shorter recovery period, and reduced corneal toxicity. PMID:28503064

Melittin induces apoptotic features in Candida albicans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Cana; Lee, Dong Gun, E-mail: dglee222@knu.ac.kr

2010-03-26

Melittin is a well-known antimicrobial peptide with membrane-active mechanisms. In this study, it was found that Melittin exerted its antifungal effect via apoptosis. Candida albicans exposed to Melittin showed the increased reactive oxygen species (ROS) production, measured by DHR-123 staining. Fluorescence microscopy staining with FITC-annexin V, TUNEL and DAPI further confirmed diagnostic markers of yeast apoptosis including phosphatidylserine externalization, and DNA and nuclear fragmentation. The current study suggests that Melittin possesses an antifungal effect with another mechanism promoting apoptosis.

The inhibition of Candida species by selected essential oils and their synergism with amphotericin B.

PubMed

Rosato, Antonio; Vitali, Cesare; Gallo, Daniela; Balenzano, Luca; Mallamaci, Rosanna

2008-08-01

In this work we highlight a possible synergistic anti-Candida effect between Melaleuca alternifolia, Origanum vulgare and Pelargonium graveolens essential oils and the antifungal compound Amphotericin B. The antifungal activity was assessed using the agar dilution method in eleven Candida strains. The results obtained indicate the occurrence of a synergistic interaction between the essential oils under study and Amphotericin B. P. graveolens essential oil appeared to be the most effective, inhibiting all the Candida species evaluated by this study.

Evaluation of Amphotericin B and Chloramphenicol as Alternative Drugs for Treatment of Chytridiomycosis and Their Impacts on Innate Skin Defenses

PubMed Central

Holden, Whitney M.; Ebert, Alexander R.; Canning, Peter F.

2014-01-01

Chytridiomycosis, an amphibian skin disease caused by the emerging fungal pathogen Batrachochytrium dendrobatidis, has been implicated in catastrophic global amphibian declines. The result is an alarming decrease in amphibian diversity that is a great concern for the scientific community. Clinical trials testing potential antifungal drugs are needed to identify alternative treatments for amphibians infected with this pathogen. In this study, we quantified the MICs of chloramphenicol (800 μg/ml), amphotericin B (0.8 to 1.6 μg/ml), and itraconazole (Sporanox) (20 ng/ml) against B. dendrobatidis. Both chloramphenicol and amphotericin B significantly reduced B. dendrobatidis infection in naturally infected southern leopard frogs (Rana [Lithobates] sphenocephala), although neither drug was capable of complete fungal clearance. Long-term exposure of R. sphenocephala to these drugs did not inhibit antimicrobial peptide (AMP) synthesis, indicating that neither drug is detrimental to this important innate skin defense. However, we observed that chloramphenicol, but not amphotericin B or itraconazole, inhibited the growth of multiple R. sphenocephala skin bacterial isolates in vitro at concentrations below the MIC against B. dendrobatidis. These results indicate that treatment with chloramphenicol might dramatically alter the protective natural skin microbiome when used as an antifungal agent. This study represents the first examination of the effects of alternative antifungal drug treatments on amphibian innate skin defenses, a crucial step to validating these treatments for practical applications. PMID:24771024

Entomopathogenic Fungi as Dual Control Agents against Both the Pest Myzus persicae and Phytopathogen Botrytis cinerea

PubMed Central

Yun, Hwi-Geon; Kim, Dong-Jun; Gwak, Won-Seok; Shin, Tae-Young

2017-01-01

The green peach aphid (Myzus persicae), a plant pest, and gray mold disease, caused by Botrytis cinerea, affect vegetables and fruit crops all over the world. To control this aphid and mold, farmers typically rely on the use of chemical insecticides or fungicides. However, intensive use of these chemicals over many years has led to the development of resistance. To overcome this problem, there is a need to develop alternative control methods to suppress populations of this plant pest and pathogen. Recently, potential roles have been demonstrated for entomopathogenic fungi in endophytism, phytopathogen antagonism, plant growth promotion, and rhizosphere colonization. Here, the antifungal activities of selected fungi with high virulence against green peach aphids were tested to explore their potential for the dual control of B. cinerea and M. persicae. Antifungal activities against B. cinerea were evaluated by dual culture assays using both aerial conidia and cultural filtrates of entomopathogenic fungi. Two fungal isolates, Beauveria bassiana SD15 and Metarhizium anisopliae SD3, were identified as having both virulence against aphids and antifungal activity. The virulence of these isolates against aphids was further tested using cultural filtrates, blastospores, and aerial conidia. The most virulence was observed in the simultaneous treatment with blastospores and cultural filtrate. These results suggest that the two fungal isolates selected in this study could be used effectively for the dual control of green peach aphids and gray mold for crop protection. PMID:29138624

Extraction, Chemical Composition, and Antifungal Activity of Essential Oil of Bitter Almond

PubMed Central

Geng, Huiling; Yu, Xinchi; Lu, Ailin; Cao, Haoqiang; Zhou, Bohang; Zhou, Le; Zhao, Zhong

2016-01-01

The essential oil from the powder residual of dried bitter almond, a novel and environmentally-friendly fungicide, was successfully extracted in a 0.7% yield by hydro-distillation under optimized conditions. The chemical composition of bitter almond essential oil (BAEO) was analyzed by gas chromatography–mass spectrometry (GC–MS). Twenty-one different components representing 99.90% of the total essential oil were identified, of which benzaldehyde (62.52%), benzoic acid (14.80%), and hexadecane (3.97%) were the most abundant components. Furthermore, the in vitro and in vivo antifungal activities of BAEO against common plant pathogenic fungi were evaluated by the mycelium linear growth rate method and pot test, respectively. It was documented that 1 mg/mL of BAEO could variously inhibit all tested pathogenic fungi with the inhibition rates of 44.8%~100%. Among the tested 19 strains of fungi, the median effective concentration (EC50) values of BAEO against Alternaria brassicae and Alternaria solani were only 50.2 and 103.2 μg/mL, respectively, which were higher than those of other fungi. The in vivo antifungal activity of BAEO against Gloeosporium orbiculare was much higher than Blumeria graminis. The protective efficacy for the former was up to 98.07% at 10 mg/mL and the treatment efficacy was 93.41% at 12 mg/mL. The above results indicated that BAEO has the great potential to be developed as a botanical and agricultural fungicide. PMID:27589723

Yeast Colonization and Drug Susceptibility Pattern in the Pediatric Patients With Neutropenia

PubMed Central

Haddadi, Pedram; Zareifar, Soheila; Badiee, Parisa; Alborzi, Abdolvahab; Mokhtari, Maral; Zomorodian, Kamiar; Pakshir, Keyvan; Jafarian, Hadis

2014-01-01

Background: Pediatric patients with neutropenia are vulnerable to invasive Candida infections. Candida is the primary cause of fungal infections, particularly in immunosuppressed patients. Candida albicans has been the most common etiologic agent of these infections, affecting 48% of patients Objectives: The aim of this study was to identify Candida spp. isolated from children with neutropenia and determine the antifungal susceptibility pattern of the isolated yeasts. Patients and Methods: In this study 188 children with neutropenia were recruited, fungal surveillance cultures were carried out on nose, oropharynx, stool, and urine samples. Identification of Candida strains was performed using germ tube and chlamydospore production tests on an API 20 C AUX system. Susceptibility testing on seven antifungal agents was performed using the agar-based E-test method. Results: A total of 229 yeasts were isolated. Among those, C. albicans was the most common species followed by C. krusei, C. parapsilosis, C. glabrata, C. tropicalis, C. famata, C. dubliniensis, C. kefyr, and other Candida species. C. glabrata was the most resistant isolated yeasts, which was 70% resistant to fluconazole and 50% to itraconazole, 7.5% to amphotericin B and 14% to ketoconazole. All the tested species were mostly sensitive to caspofungin. Conclusions: Knowledge about the susceptibility patterns of colonized Candida spp. can be helpful for clinicians to manage pediatric patients with neutropenia. In this study, caspofungin was the most effective antifungal agent against the colonized Candida spp. followed by conventional amphotericin B. PMID:25485060

Isolation and Molecular Characterization of a Model Antagonistic Pseudomonas aeruginosa Divulging In Vitro Plant Growth Promoting Characteristics.

PubMed

Uzair, Bushra; Kausar, Rehana; Bano, Syeda Asma; Fatima, Sammer; Badshah, Malik; Habiba, Ume; Fasim, Fehmida

2018-01-01

The use of microbial technologies in agriculture is currently expanding quite rapidly with the identification of new bacterial strains, which are more effective in promoting plant growth. In the present study 18 strains of Pseudomonas were isolated from soil sample of Balochistan coastline. Among isolated Pseudomonas strains four designated as SP19, SP22, PS24, and SP25 exhibited biocontrol activities against phytopathogenic fungi, that is, Rhizopus microsporus, Fusarium oxysporum, Aspergillus niger, Alternaria alternata, and Penicillium digitatum ; PS24 identified as Pseudomonas aeruginosa by 16srRNA gene bank accession number EU081518 was selected on the basis of its antifungal activity to explore its potential as plant growth promotion. PS24 showed multiple plant growth promoting attributes such as phosphate solubilization activity, indole acetic acid (IAA), siderophore, and HCN production. In order to determine the basis for antifungal properties, antibiotics were extracted from King B broth of PS24 and analyzed by TLC. Pyrrolnitrin antibiotic was detected in the culture of strain PS24. PS24 exhibited antifungal activities found to be positive for hydrogen cyanide synthase Hcn BC gene. Sequencing of gene of Hcn BC gene of strain PS24 revealed 99% homology with the Pseudomonas aeruginosa strain PA01 . The sequence of PS24 had been submitted in gene bank accession number KR605499. Ps. aeruginosa PS24 with its multifunctional biocontrol possessions can be used to bioprotect the crop plants from phytopathogens.

Entomopathogenic Fungi as Dual Control Agents against Both the Pest Myzus persicae and Phytopathogen Botrytis cinerea.

PubMed

Yun, Hwi-Geon; Kim, Dong-Jun; Gwak, Won-Seok; Shin, Tae-Young; Woo, Soo-Dong

2017-09-01

The green peach aphid ( Myzus persicae ), a plant pest, and gray mold disease, caused by Botrytis cinerea , affect vegetables and fruit crops all over the world. To control this aphid and mold, farmers typically rely on the use of chemical insecticides or fungicides. However, intensive use of these chemicals over many years has led to the development of resistance. To overcome this problem, there is a need to develop alternative control methods to suppress populations of this plant pest and pathogen. Recently, potential roles have been demonstrated for entomopathogenic fungi in endophytism, phytopathogen antagonism, plant growth promotion, and rhizosphere colonization. Here, the antifungal activities of selected fungi with high virulence against green peach aphids were tested to explore their potential for the dual control of B. cinerea and M. persicae . Antifungal activities against B. cinerea were evaluated by dual culture assays using both aerial conidia and cultural filtrates of entomopathogenic fungi. Two fungal isolates, Beauveria bassiana SD15 and Metarhizium anisopliae SD3, were identified as having both virulence against aphids and antifungal activity. The virulence of these isolates against aphids was further tested using cultural filtrates, blastospores, and aerial conidia. The most virulence was observed in the simultaneous treatment with blastospores and cultural filtrate. These results suggest that the two fungal isolates selected in this study could be used effectively for the dual control of green peach aphids and gray mold for crop protection.

Extraction, Chemical Composition, and Antifungal Activity of Essential Oil of Bitter Almond.

PubMed

Geng, Huiling; Yu, Xinchi; Lu, Ailin; Cao, Haoqiang; Zhou, Bohang; Zhou, Le; Zhao, Zhong

2016-08-29

The essential oil from the powder residual of dried bitter almond, a novel and environmentally-friendly fungicide, was successfully extracted in a 0.7% yield by hydro-distillation under optimized conditions. The chemical composition of bitter almond essential oil (BAEO) was analyzed by gas chromatography-mass spectrometry (GC-MS). Twenty-one different components representing 99.90% of the total essential oil were identified, of which benzaldehyde (62.52%), benzoic acid (14.80%), and hexadecane (3.97%) were the most abundant components. Furthermore, the in vitro and in vivo antifungal activities of BAEO against common plant pathogenic fungi were evaluated by the mycelium linear growth rate method and pot test, respectively. It was documented that 1 mg/mL of BAEO could variously inhibit all tested pathogenic fungi with the inhibition rates of 44.8%~100%. Among the tested 19 strains of fungi, the median effective concentration (EC50) values of BAEO against Alternaria brassicae and Alternaria solani were only 50.2 and 103.2 μg/mL, respectively, which were higher than those of other fungi. The in vivo antifungal activity of BAEO against Gloeosporium orbiculare was much higher than Blumeria graminis. The protective efficacy for the former was up to 98.07% at 10 mg/mL and the treatment efficacy was 93.41% at 12 mg/mL. The above results indicated that BAEO has the great potential to be developed as a botanical and agricultural fungicide.

Antifungal sourdough lactic acid bacteria as biopreservation tool in quinoa and rice bread.

PubMed

Axel, Claudia; Brosnan, Brid; Zannini, Emanuele; Furey, Ambrose; Coffey, Aidan; Arendt, Elke K

2016-12-19

The use of sourdough fermented with specific strains of antifungal lactic acid bacteria can reduce chemical preservatives in bakery products. The main objective of this study was to investigate the production of antifungal carboxylic acids after sourdough fermentation of quinoa and rice flour using the antifungal strains Lactobacillus reuteri R29 and Lactobacillus brevis R2Δ as bioprotective cultures and the non-antifungal L. brevis L1105 as a negative control strain. The impact of the fermentation substrate was evaluated in terms of metabolic activity, acidification pattern and quantity of antifungal carboxylic acids. These in situ produced compounds (n=20) were extracted from the sourdough using a QuEChERS method and detected by a new UHPLC-MS/MS chromatography. Furthermore, the sourdough was applied in situ using durability tests against environmental moulds to investigate the biopreservative potential to prolong the shelf life of bread. Organic acid production and TTA values were lowest in rice sourdough. The sourdough fermentation of the different flour substrates generated a complex and significantly different profile of carboxylic acids. Extracted quinoa sourdough detected the greatest number of carboxylic acids (n=11) at a much higher concentration than what was detected from rice sourdough (n=9). Comparing the lactic acid bacteria strains, L. reuteri R29 fermented sourdoughs contained generally higher concentrations of acetic and lactic acid but also the carboxylic acids. Among them, 3-phenyllactic acid and 2-hydroxyisocaproic acid were present at a significant concentration. This was correlated with the superior protein content of quinoa flour and its high protease activity. With the addition of L. reuteri R29 inoculated sourdough, the shelf life was extended by 2 days for quinoa (+100%) and rice bread (+67%) when compared to the non-acidified controls. The L. brevis R2Δ fermented sourdough bread reached a shelf life of 4 days for quinoa (+100%) and rice (+33%). However, the shelf life was similar to the chemically acidified control indicating that the preservation effect of the carboxylic acids seems to have a minor contribution effect on the antifungal activity in gluten-free breads. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-Aspergillus activity of green coffee 5-O-caffeoyl quinic acid and its alkyl esters.

PubMed

Suárez-Quiroz, M L; Alonso Campos, A; Valerio Alfaro, G; González-Ríos, O; Villeneuve, P; Figueroa-Espinoza, M C

2013-01-01

The antifungal activities of 5-O-caffeoyl quinic acid (5-CQA) and of methyl, butyl, octyl, and dodecyl esters or 5-CQA, were tested on five toxigenic moulds from the Aspergillus genus (Aspergillus flavus, Aspergillus nomius, Aspergillus ochraceus, Aspergillus parasiticus, Aspergillus westerdijkiae). These mycotoxin producers' moulds may contaminate many types of food crops throughout the food chain posing serious health hazard to animals and humans. The use of chemical methods to decrease mycotoxin producer moulds contamination on food crops in the field, during storage, and/or during processing, has been proved to be efficient. In this work, the antifungal effect of 5-CQA and a homologous series of 5-CQA esters (methyl, butyl, octyl, dodecyl), was investigated using the microdilution method and the minimum inhibitory concentrations (MIC50 and MIC80). All molecules presented antifungal activity, and two esters showed a MIC for all fungi: octyl (MIC50 ≤ 0.5-0.75 mg/mL, MIC80 = 1.0-1.5 mg/mL) and dodecyl (MIC50 = 0.75-1.25 mg/mL) chlorogenates. Dodecyl chlorogenate showed a MIC80 (1.5 mg/mL) only for A. parasiticus. The maximum percent of growth inhibition on aspergillii was observed with octyl (78.4-92.7%) and dodecyl (54.5-83.7%) chlorogenates, being octyl chlorogenate the most potent antifungal agent. It was thus concluded that lipophilization improved the antifungal properties of 5-CQA, which increased with the ester alkyl chain length, exhibiting a cut-off effect at 8 carbons. As far as we know, it is the first report demonstrating that lipophilization may improve the antifungal activity of 5-CQA on five toxigenic moulds from the Aspergillus genus. Lipophilization would be a novel way to synthesize a new kind of antifungal agents with a good therapeutic value or a potential use as preservative in food or cosmetics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the antifungal effect of EDTA, a metal chelator agent, on Candida albicans biofilm.

PubMed

Casalinuovo, I A; Sorge, R; Bonelli, G; Di Francesco, P

2017-03-01

Candida albicans biofilm is frequently found on artificial surfaces and the infections related to biofilm are difficult to eliminate, as they require the removal of artificial devices and treatment with antifungal drugs. Nowadays, fungal growth in biofilms is difficult to eradicate with conventional antifungal drugs such as fluconazole. Among chelating agents, disodium salt-Ethylene Diamine Tetraacetic Acid (EDTA) is known to have antifungal activity. In this study, we examined the in vitro activity of the EDTA and the antifungal drug fluconazole against C. albicans mature biofilm. C. albicans ATCC 20191, fluconazole-susceptible strain, was grown at an inoculum starter of 1 x 106 cells/ml for 72 h in 24-well microtiter plates and was further treated for 24 h with EDTA and/or fluconazole. Antifungal activities in biofilms were expressed as reduction in optical density (OD) determined by a 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay and compared to untreated biofilms. Colorimetric readings revealed that EDTA alone (at 25 and 2.5 mM) significantly reduced fungal metabolic activity in preformed biofilms. Also, EDTA combined with fluconazole significantly reduced the growth of biofilm when compared to biofilm treated with fluconazole alone (at 25 and 2.5 µg/ml). Our data suggest that the employment of EDTA or other chemicals destabilizers of the biofilm matrix, in combination with antifungal drugs, could lead to the development of new strategies for the management of infections associated to Candida biofilm. Another relevant result of our study suggests that the initial cell concentration, probably through mechanisms of quorum sensing, affects the cellular viability during the process of biofilm formation.

Antifungal coatings based on Ca(OH)2 mixed with ZnO/TiO2 nanomaterials for protection of limestone monuments.

PubMed

Gómez-Ortíz, Nikte; De la Rosa-García, Susana; González-Gómez, William; Soria-Castro, Montserrat; Quintana, Patricia; Oskam, Gerko; Ortega-Morales, Benjamin

2013-03-13

The presence and deteriorating action of microbial biofilms on historic stone buildings have received considerable attention in the past few years. Among microorganisms, fungi are one of the most damaging groups. In the present work, antimicrobial surfaces were prepared using suspensions of Ca(OH)2 particles, mixed with ZnO or TiO2 nanoparticles. The antimicrobial surfaces were evaluated for their antifungal activity both in the dark and under simulated natural photoperiod cycles, using Penicillium oxalicum and Aspergillus niger as model organisms, and two limestone lithotypes commonly used in construction and as materials for the restoration of historic buildings. Both Ca(OH)2-ZnO and Ca(OH)2-TiO2 materials displayed antifungal activity: ZnO-based systems had the best antifungal properties, being effective both in the dark and under illumination. In contrast, TiO2-based coatings showed antifungal activity only under photoperiod conditions. Controls with coatings consisting of only Ca(OH)2 were readily colonized by both fungi. The antifungal activity was monitored by direct observation with microscope, X-ray diffraction (XRD), and scanning electron microscopy (SEM), and was found to be different for the two lithotypes, suggesting that the mineral grain distribution and porosity played a role in the activity. XRD was used to investigate the formation of biominerals as indicator of the fungal attack of the limestone materials, while SEM illustrated the influence of porosity of both the limestone material and the coatings on the fungal penetration into the limestone. The coated nanosystems based on Ca(OH)2-50%ZnO and pure zincite nanoparticulate films have promising performance on low porosity limestone, showing good antifungal properties against P. oxalicum and A. niger under simulated photoperiod conditions.

Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii.

PubMed

Chen, Yuan; Farrer, Rhys A; Giamberardino, Charles; Sakthikumar, Sharadha; Jones, Alexander; Yang, Timothy; Tenor, Jennifer L; Wagih, Omar; Van Wyk, Marelize; Govender, Nelesh P; Mitchell, Thomas G; Litvintseva, Anastasia P; Cuomo, Christina A; Perfect, John R

2017-03-07

The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis. IMPORTANCE Opportunistic infections caused by species of the pathogenic yeast Cryptococcus lead to chronic meningoencephalitis and continue to ravage thousands of patients with HIV/AIDS. Despite receiving antifungal treatment, over 10% of patients develop recurrent disease. In this study, we collected isolates of Cryptococcus from cerebrospinal fluid specimens of 18 patients at the time of their diagnosis and when they relapsed several months later. We then sequenced and compared the genomic DNAs of each pair of initial and relapse isolates. We also tested the isolates for several key properties related to cryptococcal virulence as well as for their susceptibility to the antifungal drug fluconazole. These analyses revealed that the relapsing isolates manifested multiple genetic and chromosomal changes that affected a variety of genes implicated in the pathogenicity of Cryptococcus or resistance to fluconazole. This application of comparative genomics to serial clinical isolates provides a blueprint for identifying the mechanisms whereby pathogenic microbes adapt within patients to prolong disease. Copyright © 2017 Chen et al.

Essential oil composition, phytotoxic and antifungal activities of Ruta chalepensis L. leaves from High Atlas Mountains (Morocco).

PubMed

Bouajaj, Sana; Romane, Abderrahmane; Benyamna, Abdennaji; Amri, Ismail; Hanana, Mohsen; Hamrouni, Lamia; Romdhane, Mehrez

2014-01-01

This study aimed at the determination of chemical composition of essential oil obtained by hydrodistillation, and to evaluate their phytotoxic and antifungal activities. Leaves of Ruta chalepensis L. were collected from the region of Tensift Al Haouz (High Atlas Mountains) Marrakech, Morocco. The essential oil (oil yield is 0.56%) was analysed by GC-FID and GC/MS. Twenty-two compounds were identified and accounted for 92.4% of the total oil composition. The major components were undecan-2-one (49.08%), nonan-2-one (33.15%), limonene (4.19%) and decanone (2.71%). Antifungal ability of essential oils was tested by disc agar diffusion against five plant pathogenic fungi: Fusarium proliferatum, Fusarium pseudograminearum, Fusarium culmorum, Fusarium graminearum and Fusarium polyphialidicum. The oils were also tested in vitro for herbicidal activity by determining their influence on the germination and the shoot and root growth of two weed species, Triticum durum and Phalaris canariensis L.

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov.

PubMed Central

Siqueira, J. P. Z.; Sutton, D. A.; García, D.; Wiederhold, N.; Peterson, S. W.; Guarro, J.

2017-01-01

ABSTRACT A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the United States and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were the internal transcribed spacer (ITS) region, and fragments of the beta-tubulin (BenA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes. The drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A. pseudosclerotiorum (23.5%). Other species identified were A. sclerotiorum (17.6%), A. ochraceus (8.8%), A. subramanianii (8.8%), and A. insulicola and A. ochraceopetaliformis, with two isolates (5.9%) of each. The drugs that showed the most potent activity were caspofungin, micafungin, and terbinafine, while amphotericin B showed the least activity. PMID:28053212

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov.

PubMed

Siqueira, J P Z; Sutton, D A; Gené, J; García, D; Wiederhold, N; Peterson, S W; Guarro, J

2017-03-01

A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the United States and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were the internal transcribed spacer (ITS) region, and fragments of the beta-tubulin ( BenA ), calmodulin ( CaM ), and RNA polymerase II second largest subunit ( RPB2 ) genes. The drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A. pseudosclerotiorum (23.5%). Other species identified were A. sclerotiorum (17.6%), A. ochraceus (8.8%), A. subramanianii (8.8%), and A. insulicola and A. ochraceopetaliformis , with two isolates (5.9%) of each. The drugs that showed the most potent activity were caspofungin, micafungin, and terbinafine, while amphotericin B showed the least activity. Copyright © 2017 American Society for Microbiology.

Caryolan-1-ol, an antifungal volatile produced by Streptomyces spp., inhibits the endomembrane system of fungi.

PubMed

Cho, Gyeongjun; Kim, Junheon; Park, Chung Gyoo; Nislow, Corey; Weller, David M; Kwak, Youn-Sig

2017-07-01

Streptomyces spp. have the ability to produce a wide variety of secondary metabolites that interact with the environment. This study aimed to discover antifungal volatiles from the genus Streptomyces and to determine the mechanisms of inhibition. Volatiles identified from Streptomyces spp. included three major terpenes, geosmin, caryolan-1-ol and an unknown sesquiterpene. antiSMASH and KEGG predicted that the volatile terpene synthase gene clusters occur in the Streptomyces genome. Growth inhibition was observed when fungi were exposed to the volatiles. Biological activity of caryolan-1-ol has previously not been investigated. Fungal growth was inhibited in a dose-dependent manner by a mixture of the main volatiles, caryolan-1-ol and the unknown sesquiterpene, from Streptomyces sp. S4-7. Furthermore, synthesized caryolan-1-ol showed similar antifungal activity. Results of chemical-genomics profiling assays showed that caryolan-1-ol affected the endomembrane system by disrupting sphingolipid synthesis and normal vesicle trafficking in the fungi. © 2017 The Authors.

Antifungal effect of volatile organic compounds produced by Bacillus amyloliquefaciens CPA-8 against fruit pathogen decays of cherry.

PubMed

Gotor-Vila, A; Teixidó, N; Di Francesco, A; Usall, J; Ugolini, L; Torres, R; Mari, M

2017-06-01

The present work focuses on the antifungal effect of volatile organic compounds (VOCs) produced by Bacillus amyloliquefaciens CPA-8 against Monilinia laxa, M. fructicola and Botrytis cinera, three postharvest fruit pathogens of sweet cherry fruit. VOCs were evaluated with a double petri dish assay against mycelial and colony growth of target pathogens. For this purpose, CPA-8 was grown on different media and cultured for 24 and 48 h at 30 °C before assays. Data showed that mycelial growth inhibition was higher when CPA-8 was grown on Tryptone Soya Agar (TSA) while no differences were generally observed when CPA-8 was cultured for either, 24 and 48 h. Moreover, no effects were observed on colony growth. The main volatile compounds emitted by CPA-8 were identified by solid-phase microextraction (SPME)-gas chromatography as 1,3 pentadiene, acetoin (3-hydroxy-2-butanone) and thiophene. Pure compounds were also tested in vitro on mycelial growth inhibition and their EC 50 values against the three pathogens were estimated. Thiophene was the most effective VOC, showing more than 82% suppression of mycelial growth at the highest concentration (1.35 μL/mL headspace) and EC 50 values ranging from 0.06 to 6.67 μL/mL headspace. Finally, the effectiveness of thiophene and CPA-8 VOCs was evaluated against artificially inoculated cherry fruits. Among the target pathogens, M. fructicola was clearly controlled by CPA-8 with less than 25% of rotten fruits compared to the control (65% disease incidence) and for all pathogens, less than 37.5% of CPA-8 treated decayed fruits produced spores (disease sporulation). Otherwise, pure thiophene showed no effect against any pathogen on disease incidence and disease sporulation. The results indicated that VOCs produced by B. amyloliquefaciens CPA-8 could develop an additive antifungal effect against postharvest fruit pathogens on stone fruit. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of Four Calcium Channel Blockers as Fluconazole Resistance Inhibitors in Candida glabrata.

PubMed

Alnajjar, Lina M; Bulatova, Nailya R; Darwish, Rula M

2018-04-14

In this study we aimed to evaluate the ability of four calcium channel blockers, verapamil, diltiazem, nicardipine and nifedipine to enhance sensitivity of Candida glabrata strains to fluconazole. The synergistic antifungal effect was examined by checkerboard method; fractional inhibitory concentration index (FIC) was determined. Time-kill curve method was used for the most promising combination to further evaluate the synergetic effects. nicardipine showed additive effect with fluconazole against fluconazole-resistant and fluconazole-susceptible-dose-dependent strains (DSY565 and CBS138) known to express efflux pumps but not against fluconazole-sensitive strains. Nifedipine exhibited additive effect with fluconazole in both checkerboard (0.5< FIC <1) and time-kill curve methods (<2 log10 colony-forming units (CFU)/ml decrease in viable count). Additionally, nifedipine had own antifungal effect consistently against most of the strains used in this study with minimum inhibitory concentration of 8μg/ml. nicardipine showed additive effect with fluconazole in fluconazole-resistant strains of Candida glabrata-most probably via efflux pump inhibition as demonstrated selectively in fluconazole-resistant strains with known efflux pumps. Nifedipine displayed promising antifungal effect alone and additive effects with fluconazole. Copyright © 2018. Published by Elsevier Ltd.

Mode of action for reproductive and hepatic toxicity inferred from a genomic study of triazole antifungals.

PubMed

Goetz, Amber K; Dix, David J

2009-08-01

The mode of action for the reproductive toxicity of some triazole antifungals has been characterized as an increase in serum testosterone and hepatic response, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these potential modes of action, gene expression profiling was conducted on liver and testis from male Wistar Han IGS rats exposed to myclobutanil (500, 2000 ppm), propiconazole (500, 2500 ppm), or triadimefon (500, 1800 ppm) from gestation day six to postnatal day 92. Gene expression profiles indicated that all three triazoles significantly perturbed the fatty acid, steroid, and xenobiotic metabolism pathways in the male rat liver. In addition, triadimefon modulated expression of genes in the liver from the sterol biosynthesis pathway. Although expression of individual genes were affected, there were no common pathways modulated by all three triazoles in the testis. The pathways identified in the liver included numerous genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Cyp3a2, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pcx, Ppap2b), and steroid metabolism (Ugt1a1, Ugt2a1) for which expression was altered by the triazoles. These differentially expressed genes form part of a network involving lipid, sterol, and steroid homeostatic pathways regulated by the constitutive androstane (CAR), pregnane X (PXR), peroxisome proliferator-activated alpha, and other nuclear receptors in liver. These relatively high dose and long-term exposures to triazole antifungals appeared to perturb fatty acid and steroid metabolism in the male rat liver predominantly through the CAR and PXR signaling pathways. These toxicogenomic effects describe a plausible series of key events contributing to the disruption in steroid homeostasis and reproductive toxicity of select triazole antifungals.

Pathogenesis and host defence against Mucorales: the role of cytokines and interaction with antifungal drugs.

PubMed

Roilides, Emmanuel; Antachopoulos, Charalampos; Simitsopoulou, Maria

2014-12-01

Innate immune response, including macrophages, neutrophils and dendritic cells and their respective receptors, plays an important role in host defences against Mucorales with differential activity against specific fungal species, while adaptive immunity is not the first line of defence. A number of endogenous and exogenous factors, such as cytokines and growth factors as well as certain antifungal agents have been found that they influence innate immune response to these organisms. Used alone or especially in combination have been shown to exert antifungal effects against Mucorales species. These findings suggest novel ways of adjunctive therapy for patients with invasive mucormycosis. © 2014 Blackwell Verlag GmbH.

Growth Promotion and Disease Suppression Ability of a Streptomyces sp. CB-75 from Banana Rhizosphere Soil

PubMed Central

Chen, Yufeng; Zhou, Dengbo; Qi, Dengfeng; Gao, Zhufen; Xie, Jianghui; Luo, Yanping

2018-01-01

An actinomycete strain, CB-75, was isolated from the soil of a diseased banana plantation in Hainan, China. Based on phenotypic and molecular characteristics, and 99.93% sequence similarity with Streptomyces spectabilis NBRC 13424 (AB184393), the strain was identified as Streptomyces sp. This strain exhibited broad-spectrum antifungal activity against 11 plant pathogenic fungi. Type I polyketide synthase (PKS-I) and non-ribosomal peptide synthetase (NRPS) were detected, which were indicative of the antifungal compounds that Streptomyces sp. CB-75 could produce. An ethyl acetate extract from the strain exhibited the lowest minimum inhibitory concentration (MIC) against Colletotrichum musae (ATCC 96167) (0.78 μg/ml) and yielded the highest antifungal activity against Colletotrichum gloeosporioides (ATCC 16330) (50.0 μg/ml). Also, spore germination was significantly inhibited by the crude extract. After treatment with the crude extract of Streptomyces sp. CB-75 at the concentration 2 × MIC, the pathogenic fungi showed deformation, shrinkage, collapse, and tortuosity when observed by scanning electron microscopy (SEM). By gas chromatography-mass spectrometry (GC-MS) of the crude extract, 18 chemical constituents were identified; (Z)-13-docosenamide was the major constituent. Pot experiments showed that the incidence of banana seedlings was reduced after using Streptomyces sp. CB-75 treatment. The disease index was 10.23, and the prevention and control effect was 83.12%. Furthermore, Streptomyces sp. CB-75 had a growth-promoting effect on banana plants. The chlorophyll content showed 88.24% improvement, the leaf area, root length, root diameter, plant height, and stem showed 88.24, 90.49, 136.17, 61.78, and 50.98% improvement, respectively, and the shoot fresh weight, root fresh weight, shoot dry weight, and root dry weight showed 82.38, 72.01, 195.33, and 113.33% improvement, respectively, compared with treatment of fermentation broth without Streptomyces sp. CB-75. Thus, Streptomyces sp. CB-75 is an important microbial resource as a biological control against plant pathogenic fungi and for promoting banana growth. PMID:29387049

Antifungal activity of different neem leaf extracts and the nimonol against some important human pathogens

PubMed Central

Mahmoud, D.A.; Hassanein, N.M.; Youssef, K.A.; Abou Zeid, M.A.

2011-01-01

This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15 and 20%) prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC) analysis of ethyl acetate extract showed the presence of a main component (nimonol) which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens. PMID:24031718

Antifungal effect of gaseous nitric oxide on mycelium growth, sporulation and spore germination of the postharvest horticulture pathogens, Aspergillus niger, Monilinia fructicola and Penicillium italicum.

PubMed

Lazar, E E; Wills, R B H; Ho, B T; Harris, A M; Spohr, L J

2008-06-01

To evaluate the antifungal activity of nitric oxide (NO) against the growth of the postharvest horticulture pathogens Aspergillus niger, Monilinia fructicola and Penicillium italicum under in vitro conditions. Different volumes of NO gas were injected into the Petri dish headspace to obtain the desired concentrations of 50-500 microl l(-1). The growth of the fungi was measured for 8 days of incubation in air at 25 degrees C. All concentrations of NO were found to produce an antifungal effect on spore germination, sporulation and mycelial growth of the three fungi, with the most effective concentration for A. niger and P. italicum being 100 and 500 microl l(-1) for M. fructicola. Short-term exposure to a low concentration of NO gas was able to inhibit the subsequent growth of A. niger, M. fructicola and P. italicum. NO gas has potential use as a natural fungicide to inhibit microbial growth on postharvest fruit and vegetables.

Lavandula luisieri essential oil as a source of antifungal drugs.

PubMed

Zuzarte, M; Gonçalves, M J; Cruz, M T; Cavaleiro, C; Canhoto, J; Vaz, S; Pinto, E; Salgueiro, L

2012-12-01

This work reports the antifungal activity of Lavandula luisieri essential oils against yeast, dermatophyte and Aspergillus strains responsible for human infections and food contamination. The oil's cytotoxicity and its effect on the yeast-mycelium transition in Candida albicans, an important virulence factor, were also evaluated. Analyses by GC and GC/MS showed a peculiar composition of irregular monoterpenes. Significant differences between the samples occurred in the amounts of 1,8-cineole, fenchone and trans-α-necrodyl acetate. The oil with higher amounts of irregular monoterpenes was the most effective. The influence of the oils on the dimorphic transition in C. albicans was also studied through the germ tube inhibition assay. Filamentation was completely inhibited at concentrations sixteen times lower than the minimal inhibitory concentration. The results support the use of L. luiseiri essential oils in the development of new phytopharmaceuticals and food preservatives and emphasise its antifungal properties at concentrations not cytotoxic or with very low detrimental effects on mammalian cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Amphotericin B-silver hybrid nanoparticles: synthesis, properties and antifungal activity.

PubMed

Tutaj, Krzysztof; Szlazak, Radoslaw; Szalapata, Katarzyna; Starzyk, Joanna; Luchowski, Rafal; Grudzinski, Wojciech; Osinska-Jaroszuk, Monika; Jarosz-Wilkolazka, Anna; Szuster-Ciesielska, Agnieszka; Gruszecki, Wieslaw I

2016-05-01

High antifungal activity is reported, in comparison with commercially available products, of a novel hybrid system based on silver nanoparticles synthesized using a popular antifungal macrocyclic polyene amphotericin B (AmB) acting both as a reducing and stabilizing/capping agent. The synthesis reaction proceeds in an alkaline environment which prevents aggregation of AmB itself and promotes nanoparticle formation. The innovative approach produces monodisperse (PDI=0.05), AmB-coated silver nanoparticles (AmB-AgNPs) with the diameter ~7nm. The products were characterized using imaging (electron microscopy) and spectroscopic (UV-vis and infrared absorption, dynamic light scattering and Raman scattering) methods. The nanoparticles were tested against Candida albicans, Aspergillus niger and Fusarium culmorum species. For cytotoxicity studies CCD-841CoTr and THP-1 cell lines were used. Particularly high antifungal activity of AmB-AgNPs is interpreted as the result of synergy between the antifungal activity of amphotericin B and silver antimicrobial properties (Ag(+) ions release). Amphotericin B (AmB) is a common agent used for the treatment against severe fungal infections. In this article, the authors described a new approach in using a combination of AmB and silver nanoparticles, in which the silver nanoparticles were synthesized and stabilized by AmB. Experimental data confirmed synergistic antifungal effects between amphotericin B and silver. This novel synthesis process could potentially be important in future drug development and fabrication. Copyright © 2016 Elsevier Inc. All rights reserved.

Antifungal properties of peptidomimetics with an arginine-[β-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii.

PubMed

Larsen, Camilla Eggert; Larsen, Camilla Josephine; Franzyk, Henrik; Regenberg, Birgitte

2015-05-01

Due to increased occurrence of infections and food spoilage caused by yeast, there is an unmet need for new antifungal agents. The arginine-β-(2,5,7-tri-tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved useful in the design of an antifungal tripeptide. Here, an array of peptidomimetics based on this motif was investigated for antifungal and hemolytic activity. The five most promising modified tetrapeptide analogues ( 6: and 9-12: contain an additional C-terminal hydrophobic residue, and these were found to exhibit antifungal activity against Saccharomyces cerevisiae (MIC 6 and 12 μg mL(-1)) and Zygosaccharomyces bailii (MIC 6-25 μg mL(-1)). Four compounds ( 6: and 9-11: , had limited hemolytic activity (<10% hemolysis at 8 × MIC). Determination of their killing kinetics revealed that compound 9: displayed fungicidal effect. Testing against cells from an S. cerevisiae deletion mutant library indicated that interaction with yeast-specific fungal sphingolipids, most likely constitutes a crucial step in the mode of action. Interestingly, a lack of activity of peptidomimetics 6: and 9-11: towards Candida spp. was shown to be due to degradation or sequestering by the yeast. Due to their ultrashort nature, antifungal activity and low toxicity, the four compounds may have potential as leads for novel preservatives. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antifungal susceptibilities of Candida species isolated from urine culture.

PubMed

Toka Özer, Türkan; Durmaz, Süleyman; Yula, Erkan

2016-09-01

Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Dynamics of Mixed- Candida Species Biofilms in Response to Antifungals.

PubMed

Vipulanandan, G; Herrera, M; Wiederhold, N P; Li, X; Mintz, J; Wickes, B L; Kadosh, D

2018-01-01

Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.

Evidence-based Danish guidelines for the treatment of Malassezia-related skin diseases.

PubMed

Hald, Marianne; Arendrup, Maiken C; Svejgaard, Else L; Lindskov, Rune; Foged, Erik K; Saunte, Ditte Marie L

2015-01-01

Internationally approved guidelines for the diagnosis and management of Malassezia-related skin diseases are lacking. Therefore, a panel of experts consisting of dermatologists and a microbiologist under the auspices of the Danish Society of Dermatology undertook a data review and compiled guidelines for the diagnostic procedures and management of pityriasis versicolor, seborrhoeic dermatitis and Malassezia folliculitis. Main recommendations in most cases of pityriasis versicolor and seborrhoeic dermatitis include topical treatment which has been shown to be sufficient. As first choice, treatment should be based on topical antifungal medication. A short course of topical corticosteroid or topical calcineurin inhibitors has an anti-inflammatory effect in seborrhoeic dermatitis. Systemic antifungal therapy may be indicated for widespread lesions or lesions refractory to topical treatment. Maintenance therapy is often necessary to prevent relapses. In the treatment of Malassezia folliculitis systemic antifungal treatment is probably more effective than topical treatment but a combination may be favourable.

Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds.

PubMed

Scorzoni, Liliana; Sangalli-Leite, Fernanda; de Lacorte Singulani, Junya; de Paula E Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

2016-04-01

In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

An inter-species signaling system mediated by fusaric acid has parallel effects on antifungal metabolite production by Pseudomonas protegens Pf-5 and antibiosis of Fusarium spp.

USDA-ARS?s Scientific Manuscript database

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that acts as a biocontrol agent of soilborne plant diseases, and produces at least seven different secondary metabolites with antifungal properties. We derived site-directed mutants of Pf-5 with single and multiple mutations in the biosynt...

Antifungal activity of extracts from Piper aduncum leaves prepared by different solvents and extraction techniques against dermatophytes Trichophyton rubrum and Trichophyton interdigitale.

PubMed

Santos, Maximillan Leite; Magalhães, Chaiana Froés; da Rosa, Marcelo Barcellos; de Assis Santos, Daniel; Brasileiro, Beatriz Gonçalves; de Carvalho, Leandro Machado; da Silva, Marcelo Barreto; Zani, Carlos Leomar; de Siqueira, Ezequias Pessoa; Peres, Rodrigo Loreto; Andrade, Anderson Assunção

2013-12-01

The effects of different solvents and extraction techniques upon the phytochemical profile and anti-Trichophyton activity of extracts from Piper aduncum leaves were evaluated. Extract done by maceration method with ethanol has higher content of sesquiterpenes and antifungal activity. This extract may be useful as an alternative treatment for dermatophytosis.

Antifungal activity of extracts from Piper aduncum leaves prepared by different solvents and extraction techniques against dermatophytes Trichophyton rubrum and Trichophyton interdigitale

PubMed Central

Santos, Maximillan Leite; Magalhães, Chaiana Froés; da Rosa, Marcelo Barcellos; de Assis Santos, Daniel; Brasileiro, Beatriz Gonçalves; de Carvalho, Leandro Machado; da Silva, Marcelo Barreto; Zani, Carlos Leomar; de Siqueira, Ezequias Pessoa; Peres, Rodrigo Loreto; Andrade, Anderson Assunção

2013-01-01

The effects of different solvents and extraction techniques upon the phytochemical profile and anti-Trichophyton activity of extracts from Piper aduncum leaves were evaluated. Extract done by maceration method with ethanol has higher content of sesquiterpenes and antifungal activity. This extract may be useful as an alternative treatment for dermatophytosis. PMID:24688522

Topical antifungal drug products for over-the-counter human use; amendment of final monograph. Final rule.

PubMed

2002-02-08

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph for over-the-counter (OTC) topical antifungal drug products to add the ingredient clotrimazole as generally recognized as safe and effective for the treatment of athlete's foot, jock itch, and ringworm. This final rule is part of FDA's ongoing review of OTC drug products.

Effects of beta-thujaplicin on anti-Malassezia pachydermatis remedy for canine otitis externa.

PubMed

Nakano, Yasuyuki; Wada, Makoto; Tani, Hiroyuki; Sasai, Kazumi; Baba, Eiichiroh

2005-12-01

The antifungal activity of beta-thujaplicin was evaluated against 51 Malassezia pachydermatis strains isolated from canine ear canals with or without otitis externa. For comparison, sensitivity tests were performed on M. pachydermatis isolates for nystatin, ketoconazole, and terbinafine HCl, all clinically available antifungal agents. The minimal inhibition concentrations over 50% of the tested isolates (MIC50) were 3.13 microg/ml for beta-thujaplicin and nystatin, 0.016 microg/ml for ketoconazole, and 1.56 microg/ml for terbinafine HCl. The antifungal effect for M. pachydermatis of beta-thujaplicin compared favorably with commercial antifungal agents. None of the 51 M. pachydermatis isolates showed resistance against any of the tested antibiotics investigated in this study. Ten representative isolates of M. pachydermatis were subcultured for 30 generations at concentrations close to the MIC levels of beta-thujaplicin, nystatin, ketoconazole, and terbinafine HCl, and examined to determine whether they had acquired resistance to each drug. As a result, M. pachydermatis was found to achieve resistance more easily for ketoconazole and terbinafine HCl than for beta-thujaplicin or nystatin. The MIC50 of beta-thujaplicin did not change during the course of subculture, and it is thought that the potential development of a resistant strain is low, even with continuous infusion for otitis externa therapy. beta-Thujaplicin is an inexpensive and safe treatment with anti-inflammatory and deodorant effects that can be recommended as an effective remedy for canine otitis externa.

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains.

PubMed

Maesaki, S; Marichal, P; Hossain, M A; Sanglard, D; Vanden Bossche, H; Kohno, S

1998-12-01

We investigated the effects of combining tacrolimus and azole antifungal agents in azole-resistant strains of Candida albicans by comparing the accumulation of [3H]itraconazole. The CDR1-expressing resistant strain C26 accumulated less itraconazole than the CaMDR-expressing resistant strain C40 or the azole-sensitive strain B2630. A CDR1-expressing Saccharomyces cerevisiae mutant, DSY415, showed a marked reduction in the accumulation of both fluconazole and itraconazole. A CaMDR-expressing S. cerevisiae mutant, DSY416, also showed lower accumulation of fluconazole, but not of itraconazole. The addition of sodium azide, an electron-transport chain inhibitor, increased the intracellular accumulation of itraconazole only in the C26 strain, and not in the C40 or B2630 strains. Addition of tacrolimus, an inhibitor of multidrug resistance proteins, resulted in the highest increase in itraconazole accumulation in the C26 strain. The combination of itraconazole and tacrolimus was synergic in azole-resistant C. albicans strains. In the C26 strain, the MIC of itraconazole decreased from >8 to 0.5 mg/L when combined with tacrolimus. Our results showed that two multidrug resistance phenotypes (encoded by the CDR1 and CaMDR genes) in C. albicans have different substrate specificity for azole antifungal agents and that a combination of tacrolimus and azole antifungal agents is effective against azole-resistant strains of C. albicans.

Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhof, Torsten; Seibold, Michael; Thewes, Sascha

This is First report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 {mu}g/ml, independently from themore » species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different.« less

The antifungal activity and membrane-disruptive action of dioscin extracted from Dioscorea nipponica.

PubMed

Cho, Jaeyong; Choi, Hyemin; Lee, Juneyoung; Kim, Mi-Sun; Sohn, Ho-Yong; Lee, Dong Gun

2013-03-01

Dioscin is a kind of steroidal saponin isolated from the root bark of wild yam Dioscorea nipponica. We investigated the antifungal effect of dioscin against different fungal strains and its antifungal mechanism(s) in Candida albicans cells. Using the propidium iodide assay and calcein-leakage measurement, we confirmed that dioscin caused fungal membrane damage. Furthermore, we evaluated the ability of dioscin to disrupt the plasma membrane potential, using 3,3'-dipropylthiadicarbocyanine iodide [DiSC(3)(5)] and bis-(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)]. Cells stained with the dyes had a significant increase in fluorescent intensity after exposure to dioscin, indicating that dioscin has an effect on the membrane potential. To visualize the effect of dioscin on the cell membrane, we synthesized rhodamine-labeled giant unilamellar vesicles (GUVs) mimicking the outer leaflet of the plasma membrane of C. albicans. As seen in the result, the membrane disruptive action of dioscin caused morphological change and rhodamine leakage of the GUVs. In three-dimensional contour-plot analysis using flow cytometry, we observed a decrease in cell size, which is in agreement with our result from the GUV assay. These results suggest that dioscin exerts a considerable antifungal activity by disrupting the structure in membrane after invading into the fungal membrane, resulting in fungal cell death. Copyright © 2012 Elsevier B.V. All rights reserved.

Antifungal activity of four honeys of different types from Algeria against pathogenic yeast: Candida albicans and Rhodotorula sp.

PubMed

Moussa, Ahmed; Noureddine, Djebli; Saad, Aissat; Abdelmelek, Meslem; Abdelkader, Benhalima

2012-07-01

To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e. Candida albicans (C. albicans) and Rhodotorula sp. Four Algeria honeys of different botanical origin were analyzed to test antifungal effect against C. albicans, and Rhodotorula sp. Different concentrations (undiluted, 10%, 30%, 50% and 70% w/v) of honey were studied in vitro for their antifugal activity using C. albicans and Rhodotorula sp. as fungal strains. The range of the diameter of zone of inhibition of various concentrations of tested honeys was (7-23 mm) for Rhodotorula sp., while C. albicans showed clearly resistance towards all concentrations used. The MICs of tested honey concentrations against C. albicans and Rhodotorula sp. were (70.09-93.48)% and (4.90-99.70)% v/v, respectively. This study demonstrates that, in vitro, these natural products have clearly an antifungal activity against Rhodotorula sp. and C. albicans.

A constitutively expressed antifungal peptide protects Tenebrio molitor during a natural infection by the entomopathogenic fungus Beauveria bassiana.

PubMed

Maistrou, Sevasti; Paris, Véronique; Jensen, Annette B; Rolff, Jens; Meyling, Nicolai V; Zanchi, Caroline

2018-09-01

Antimicrobial peptides have been well studied in the context of bacterial infections. Antifungal peptides have received comparatively less attention. Fungal pathogens of insects and their hosts represent a unique opportunity to study host-pathogen interactions due to the million of years of co-evolution they share. In this study, we investigated role of a constitutively expressed thaumatin-like peptide with antifungal activity expressed by the mealworm beetle Tenebrio molitor, named Tenecin 3, during a natural infection with the entomopathogenic fungus Beauveria bassiana. We monitored the effect of the expression of Tenecin 3 on the survival of infected hosts as well as on the progression of the fungal infection inside the host. Finally, we tested the activity of Tenecin 3 against B. bassiana. These findings could help improving biocontrol strategies and help understanding the evolution of antifungal peptides as a defense mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antitumor and antifungal activities of organic extracts of seacucumber Holothuria atra from the southeast coast of India

NASA Astrophysics Data System (ADS)

Dhinakaran, Devaraj Isaac; Lipton, Aaron Premnath

2015-02-01

In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cucumber Holothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such as Trichoderma viride, Aspergillus niger, Aspergillus flavis, Candida albicans and Penicillium chrysogenum. Relatively high antifungal activity was seen against Candida albicans at 100 μL-1 concentration of extracts. Zone of inhibition was measured at 18 mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated with H. atra extract at concentrations 0.078-10mg mL-1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber ( H. atra) showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

Combination of different antifungal agents in oil-in-water emulsions to control strawberry jam spoilage.

PubMed

Ribes, Susana; Fuentes, Ana; Talens, Pau; Barat, Jose Manuel

2018-01-15

The combination of antifungal agents (cinnamon bark oil, zinc gluconate and trans-ferulic acid) in oil-in-water emulsions to control the fungal spoilage of strawberry jams, minimising essential oil's sensory impact, was evaluated in this work. The in vitro assays of free antifungal agents were performed against five fungal strains; meanwhile, the emulsions assays were conducted against Aspergillus niger given its strong resistance and its relevance in strawberry products. The emulsion formulated with 0.08mg/g of essential oil was able to inhibit mould growth after the incubation period. The incorporation of zinc gluconate or trans-ferulic acid, independently of the concentration used, allowed to reduce a 25% the amount of essential oil needed to inhibit the microbial growth. The combination of antifungal agents in the emulsions has demonstrated to be an effective alternative to reduce the amount of essential oil employed, maintaining the hygienic quality and sensory profile of the strawberry jam. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antifungal activity of four honeys of different types from Algeria against pathogenic yeast: Candida albicans and Rhodotorula sp.

PubMed Central

Moussa, Ahmed; Noureddine, Djebli; Saad, Aissat; Abdelmelek, Meslem; Abdelkader, Benhalima

2012-01-01

Objective To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e. Candida albicans (C. albicans) and Rhodotorula sp. Methods Four Algeria honeys of different botanical origin were analyzed to test antifungal effect against C. albicans, and Rhodotorula sp. Different concentrations (undiluted, 10%, 30%, 50% and 70% w/v) of honey were studied in vitro for their antifugal activity using C. albicans and Rhodotorula sp. as fungal strains. Results The range of the diameter of zone of inhibition of various concentrations of tested honeys was (7–23 mm) for Rhodotorula sp., while C. albicans showed clearly resistance towards all concentrations used. The MICs of tested honey concentrations against C. albicans and Rhodotorula sp. were (70.09–93.48)% and (4.90–99.70)% v/v, respectively. Conclusions This study demonstrates that, in vitro, these natural products have clearly an antifungal activity against Rhodotorula sp. and C. albicans. PMID:23569970

Cyclization Reaction of Acyl Thiourea Chitosan: Enhanced Antifungal Properties via Structural Optimization.

PubMed

Qin, Yukun; Liu, Weixiang; Xing, Ronge; Liu, Song; Li, Kecheng; Li, Pengcheng

2018-03-06

In this study, 3-methyl-1,2,4-triazolyl chitosan (MTACS) and 3-chloromethyl-1,2,4-triazolyl chitosan (CMTACS) were prepared via cyclization of acyl thiourea chitosan (TUCS). Their structures were confirmed by FT-IR, ¹H-NMR, elemental analysis, DSC, XRD, and SEM. The conformations were predicted using the Gaussian 09 program. Additionally, the antifungal properties of MTACS and CMTACS against Stemphylium solani weber ( S. solani ), Alternaria porri ( A. porri ), and Gloeosporium theae-sinensis ( G. theae-sinensis ) were assayed in vitro and ranged from 250 μg/mL to 1000 μg/mL. The results showed that MTACS and CMTACS exhibited enhanced inhibitory effect on the selected fungi compared to the original chitosan and TUCS. In particular, they displayed better antifungal activities against A. porri and G. theae-sinensis than that of the positive control, Triadimefon. The findings described here may lead to them being used as antifungal agents for crop protection.

Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus▿

PubMed Central

Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Papaioannidou, Paraskevi; Tsiouris, Ioannis; Roilides, Emmanuel; Walsh, Thomas J.

2008-01-01

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 μg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis. PMID:18299413

Antifungal stewardship considerations for adults and pediatrics.

PubMed

Hamdy, Rana F; Zaoutis, Theoklis E; Seo, Susan K

2017-08-18

Antifungal stewardship refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents in order to achieve the best clinical outcomes and minimize selective pressure and adverse events. Antifungal utilization has steadily risen over time in concert with the increase in number of immunocompromised adults and children at risk for invasive fungal infections (IFI). Challenges in diagnosing IFI often lead to delays in treatment and poorer outcomes. There are also emerging data linking prior antifungal exposure and suboptimal dosing to the emergence of antifungal resistance, particularly for Candida. Antimicrobial stewardship programs can take a multi-pronged bundle approach to ensure suitable prescribing of antifungals via post-prescription review and feedback and/or prior authorization. Institutional guidelines can also be developed to guide diagnostic testing in at-risk populations; appropriate choice, dose, and duration of antifungal agent; therapeutic drug monitoring; and opportunities for de-escalation and intravenous-to-oral conversion.

[Bactericid and fungicid polymers in dentistry. Polyethyleneimine, a new effective antibacterial and antifungal cationic polymer and its dental application].

PubMed

Géczi, Zoltán; Kispélyi, Barbara; Pál, Károly; Hermann, Péter

2016-06-01

In the past years antibacterial and antifungal polymers had become the focus of medical research. Polyethylenimine (PEI) and poliamidoamin had been proven the most effective polymers. The data shown in this short review discuss the chemical structure, pharmacological effects and medical use of PEI. Report in the international literature only gives examples of experimental dental appliance of PEI in sealers and filling materials. Because of the growing interest in the subject of PEI we find it important to inform the domestic dental society of cationic polymers.

In vitro antifungal activity of silver nanoparticles against ocular pathogenic filamentous fungi.

PubMed

Xu, Yan; Gao, Chuanwen; Li, Xiaohua; He, Yi; Zhou, Lutan; Pang, Guangren; Sun, Shengtao

2013-03-01

Fungal keratitis is emerging as a major cause of vision loss in a developing country such as China because of higher incidence and the unavailability of effective antifungals. It is urgent to explore broad-spectrum antifungals to effectively suppress ocular fungal pathogens, and to develop new antifungal eye drops to combat this vision-threatening infection. The aim of this study is to investigate the antifungal activity of silver nanoparticles (nano-Ag) in comparison with that of natamycin against ocular pathogenic filamentous fungi in vitro. Susceptibility tests were performed against 216 strains of fungi isolated from patients with fungal keratitis from the Henan Eye Institute in China by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A document. The isolates included 112 Fusarium isolates (82 Fusarium solani species complex, 20 Fusarium verticillioides species complex, and 10 Fusarium oxysporum species complex), 94 Aspergillus isolates (61 Aspergillus flavus species complex, 11 Aspergillus fumigatus species complex, 12 Aspergillus versicolor species complex, and 10 Aspergillus niger species complex), and 10 Alternaria alternata isolates. The minimum inhibitory concentration (MIC) range and mode, the MIC for 50% of the strains tested (MIC50 value), and the MIC90 value were provided for the isolates with the SPSS statistical package. MIC50 value of nano-Ag were 1, 0.5, and 0.5 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of nano-Ag were 1, 1, and 1 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC50 values of natamycin were 4, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of natamycin were 8, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. Nano-Ag, relative to natamycin, exhibits potent in vitro activity against ocular pathogenic filamentous fungi.

In vitro antifungal susceptibility and molecular identity of 99 clinical isolates of the opportunistic fungal genus Curvularia.

PubMed

da Cunha, Keith C; Sutton, Deanna A; Fothergill, Annette W; Gené, Josepa; Cano, Josep; Madrid, Hugo; Hoog, Sybren de; Crous, Pedro W; Guarro, Josep

2013-06-01

The in vitro antifungal susceptibility of a set of 99 clinical isolates of Curvularia was tested against 9 drugs using a reference microdilution method. The isolates had been identified previously to species level by comparing their ITS rDNA and glyceraldehyde-3-phosphate dehydrogenase gene sequences with those of reference strains. We were able to reliably identify 73.2% of the isolates, the most frequent species being Curvularia aeria, Curvularia geniculata/Curvularia senegalensis, Curvularia lunata, Curvularia inaequalis, Curvularia verruculosa, and Curvularia borreriae. Most of these isolates had been recovered from nasal sinus, which is generally considered one of the most frequent sites of infection by these fungi. In addition, at least 3 phylogenetic species that have not yet been formally described were detected. The most active drugs were the echinocandins, amphotericin B, and posaconazole, whereas voriconazole and itraconazole showed poor activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Selection of sourdough lactobacilli with antifungal activity for use as biopreservatives in bakery products.

PubMed

Garofalo, Cristiana; Zannini, Emanuele; Aquilanti, Lucia; Silvestri, Gloria; Fierro, Olga; Picariello, Gianluca; Clementi, Francesca

2012-08-08

Two hundred and sixteen LAB cultures from sourdoughs and dough for bread and panettone production were screened for in vitro antifungal properties against three indicator cultures ascribed to Aspergillus japonicus , Eurotium repens , and Penicillium roseopurpureum , isolated from bakery environment and moldy panettone. Nineteen preselected isolates were subjected to minimum inhibitory concentration determination against the indicator cultures. Sourdoughs prepared with the two most promising strains, identified as Lactobacillus rossiae LD108 and Lactobacillus paralimentarius PB127, were characterized. The sourdough extracts were subjected to HPLC analysis coupled with a microtiter plate bioassay against A. japonicus to identify the active fractions. MALDI-TOF MS analysis revealed the occurrence of a series of peptides corresponding to wheat α-gliadin proteolysis fragments in the active fraction from L. rossiae LD108 sourdough. The ability to prevent mold growth on bread was demonstrated for both strains, whereas L. rossiae LD108 also inhibited mold growth on panettone.

Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi.

PubMed

Cho, Jun Young; Kim, Hae Young; Choi, Gyung Ja; Jang, Kyoung Soo; Lim, He Kyoung; Lim, Chi Hwan; Cho, Kwang Yun; Kim, Jin-Cheol

2006-05-01

The methanol extract of stems of Catalpa ovata G Don exhibits potent in vivo antifungal activity against Magnaporthe grisea (Hebert) Barr (rice blast) on rice plants, Botrytis cinerea Pers ex Fr (tomato grey mould) and Phytophthora infestans (Mont) de Bary (tomato late blight) on tomato plants, Puccinia recondita Rob ex Desm (wheat leaf rust) on wheat plants and Blumeria graminis (DC) Speer f. sp. hordei Marchal (barley powdery mildew) on barley plants. An antifungal substance was isolated and identified as dehydro-alpha-lapachone from mass and nuclear magnetic resonance spectral data. It completely inhibited the mycelial growth of B. cinerea, Colletotrichum acutatum Simmonds, Colletotrichum gloeosporioides Simmonds, M. grisea and Pythium ultimum Trow over a range of 0.4-33.3 mg litre(-1). It also controlled the development of rice blast, tomato late blight, wheat leaf rust, barley powdery mildew and red pepper anthracnose (Colletotrichum coccodes (Wallr) S Hughes). The chemical was particularly effective in suppressing red pepper anthracnose by 95% at a concentration of 125 mg litre(-1). Copyright 2006 Society of Chemical Industry.

Biosynthesis of silver nanoparticles by the fungus Arthroderma fulvum and its antifungal activity against genera of Candida, Aspergillus and Fusarium

PubMed Central

Xue, Baiji; He, Dan; Gao, Song; Wang, Dongyang; Yokoyama, Koji; Wang, Li

2016-01-01

The objective of this study was to find one or more fungal strains that could be utilized to biosynthesize antifungal silver nanoparticles (AgNPs). Using morphological and molecular methods, Arthroderma fulvum was identified as the most effective fungal strain for synthesizing AgNPs. The UV–visible range showed a single peak at 420 nm, which corresponded to the surface plasmon absorbance of AgNPs. X-ray diffraction and transmission electron microscopy demonstrated that the biosynthesized AgNPs were crystalline in nature with an average diameter of 15.5±2.5 nm. Numerous factors could potentially affect the process of biosynthesis, and the main factors are discussed here. Optimization results showed that substrate concentration of 1.5 mM, alkaline pH, reaction temperature of 55°C, and reaction time of 10 hours were the optimum conditions for AgNP biosynthesis. Biosynthesized AgNPs showed considerable activity against the tested fungal strains, including Candida spp., Aspergillus spp., and Fusarium spp., especially Candida spp. PMID:27217752

Chalcone dendrimer stabilized core-shell nanoparticles—a comparative study on Co@TiO2, Ag@TiO2 and Co@AgCl nanoparticles for antibacterial and antifungal activity

NASA Astrophysics Data System (ADS)

Vanathi Vijayalakshmi, R.; Praveen Kumar, P.; Selvarani, S.; Rajakumar, P.; Ravichandran, K.

2017-10-01

A series of core@shell nanoparticles (Co@TiO2, Ag@TiO2 and Co@AgCl) stabilized with zeroth generation triazolylchalcone dendrimer was synthesized using reduction transmetalation method. The coordination of chalcone dendrimer with silver ions was confirmed by UV-vis spectroscopy. The NMR spectrum ensures the number of protons and carbon signals in the chalcone dendrimer. The prepared samples were structurally characterized by XRD, FESEM and HRTEM analysis. The SAED and XRD analyses exhibited the cubic structure with d hkl   =  2.2 Å, 1.9 Å and 1.38 Å. The antibacterial and antifungal activities of the dendrimer stabilized core@shell nanoparticles (DSCSNPs) were tested against the pathogens Bacillus subtilis, Proteus mirabilis, Candida albicans and Aspergillus nigir from which it is identified that the dendrimer stabilized core shell nanoparticles with silver ions at the shell (Co@AgCl) shows effectively high activity against the tested pathogen following the other core@shell nanoparticles viz Ag@TiO2 and Co@TiO2.

Effect of ionizing energy on extracts of Quillaja saponaria to be used as an antimicrobial agent on irradiated edible coating for fresh strawberries

NASA Astrophysics Data System (ADS)

Zúñiga, G. E.; Junqueira-Gonçalves, M. P.; Pizarro, M.; Contreras, R.; Tapia, A.; Silva, S.

2012-01-01

Incorporating antimicrobial compounds into edible films or coatings provides a novel way to improve the safety and shelf life of ready-to-eat foods. Diverse studies with Quillaja saponaria Mol. (popularly named quillay) extracts have demonstrated their potential as antifungal agents against phytopathogenic fungi. Crosslinking induced by ionizing radiation is an effective method for the improvement of both barrier and mechanical properties of the edible films and coatings based on milk proteins. However there are few reports about the effects of γ-radiation on plant extracts. The aim of this work was to evaluate the effect of ionizing radiation (0, 5, 10, 15, 20, 25 and 35 kGy) on extracts prepared from in vitro plants of Q. saponaria to be used as antimicrobial agent in irradiated edible coating based on calcium caseinate and whey protein isolated, and also to establish the concentration of Q. saponaria extract to be added as an antifungal agent in the coating. Gamma irradiation since 15 kGy affects negatively the antimicrobial activity and metabolites composition of extract of Q. saponaria by reducing compounds of phenolic nature. Otherwise no effect on saponins profile was observed even at higher doses. It was possible to conclude that the antifungal activity of Q. saponaria extract is mainly related to phenolic compounds content. In addition, our work also shows that to obtain an efficient antifungal protection is necessary to add a minimum concentration of 6% of the extract after the coating irradiation.

Antifungal adjuvants: Preserving and extending the antifungal arsenal

PubMed Central

Butts, Arielle; Palmer, Glen E.; Rogers, P. David

2017-01-01

ABSTRACT As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance. PMID:27459018

Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

PubMed

de Abreu, Letícia Coli Louvisse; Todaro, Valerio; Sathler, Plinio Cunha; da Silva, Luiz Cláudio Rodrigues Pereira; do Carmo, Flávia Almada; Costa, Cleonice Marques; Toma, Helena Keiko; Castro, Helena Carla; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

2016-12-01

The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.

Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy.

PubMed

Heng, Siow-Chin; Slavin, Monica A; Al-Badriyeh, Daoud; Kirsa, Sue; Seymour, John F; Grigg, Andrew; Thursky, Karin; Bajel, Ashish; Nation, Roger L; Kong, David C M

2013-07-01

Fluconazole, posaconazole and voriconazole are used prophylactically in patients with acute myeloid leukaemia (AML). This study evaluated the clinical and economic outcomes of these agents when used in AML patients undergoing consolidation chemotherapy. A retrospective chart review (2003-10) of AML patients receiving consolidation chemotherapy was performed. Patients were followed through their first cycle of consolidation chemotherapy. Antifungal prescribing patterns, clinical outcomes and resource consumptions were recorded. A decision analytical model was developed to depict the downstream consequences of using each antifungal agent, with success defined as completion of the designated course of initial antifungal prophylaxis without developing invasive fungal disease (IFD). Cost-effectiveness and sensitivity analyses were performed. A total of 106 consecutive patients were analysed. Baseline characteristics and predisposing factors for IFD were comparable between groups. Three IFDs (one proven, one probable and one suspected) occurred, all in the posaconazole group. Patients receiving posaconazole had the highest rate of intolerance requiring drug cessation (13% versus 7% in each of the fluconazole and voriconazole groups). Fluconazole conferred overall savings per patient of 26% over posaconazole and 13% over voriconazole. Monte Carlo simulation demonstrated a mean cost saving with fluconazole of AU$8430 per patient (95% CI AU$5803-AU$11 054) versus posaconazole and AU$3681 per patient (95% CI AU$990-AU$6319) versus voriconazole. One-way sensitivity analyses confirmed the robustness of the model. This is the first study to show that, in the setting of consolidation therapy for AML, fluconazole is the most cost-effective approach to antifungal prophylaxis compared with posaconazole or voriconazole.