Sample records for promising antifungal agent
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Potential Use of Alginate-Based Carriers As Antifungal Delivery System
Spadari, Cristina de Castro; Lopes, Luciana B.; Ishida, Kelly
2017-01-01
Fungal infections have become a major public health problem, growing in number and severity in recent decades due to an increase of immunocompromised patients. The use of therapeutic agents available to treat these fungal infections is limited by their toxicity, low bioavailability, antifungal resistance, and high cost of treatment. Thus, it becomes extremely important to search for new therapeutic options. The use of polymeric systems as drug carriers has emerged as a promising alternative to conventional formulations for antifungals. Alginate is a natural polymer that has been explored in the last decade for development of drug delivery systems due to its non-toxicity, biodegradability, biocompatibility, low cost, mucoadhesive, and non-immunogenic properties. Several antifungal agents have been incorporated in alginate-based delivery systems, including micro and nanoparticles, with great success, displaying promising in vitro and in vivo results for antifungal activities, reduction in the toxicity and the total drug dose used in the treatment, and improved bioavailability. This review aims at discussing the potential use and benefits of alginate-based nanocarriers and other delivery systems containing antifungal agents in the therapy of fungal infections. PMID:28194145
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Potential Use of Phenolic Acids as Anti-Candida Agents: A Review
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
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Prevention of fungal spoilage in food products using natural compounds: A review.
Ribes, Susana; Fuentes, Ana; Talens, Pau; Barat, Jose Manuel
2017-04-10
The kingdom Fungi is the most important group of microorganism contaminating food commodities, and chemical additives are commonly used in the food industry to prevent fungal spoilage. However, the increasing consumer concern about synthetic additives has led to their substitution by natural compounds in foods. The current review provides an overview of using natural agents isolated from different sources (plants, animals, and microorganisms) as promising antifungal compounds, including information about their mechanism of action and their use in foods to preserve and prolong shelf life. Compounds derived from plants, chitosan, lactoferrin, and biocontrol agents (lactic acid bacteria, antagonistic yeast, and their metabolites) are able to control the decay caused by fungi in a wide variety of foods. Several strategies are employed to reduce the drawbacks of some antifungal agents, like their incorporation into oil-in-water emulsions and nanoemulsions, edible films and active packaging, and their combination with other natural preservatives. These strategies facilitate the addition of volatile agents into food products and, improve their antifungal effectiveness. Moreover, biological agents have been investigated as one of the most promising options in the control of postharvest decay. Numerous mechanisms of action have been elucidated and different approaches have been studied to enhance their antifungal effectiveness.
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Novel fluconazole derivatives with promising antifungal activity.
Thamban Chandrika, Nishad; Shrestha, Sanjib K; Ngo, Huy X; Howard, Kaitlind C; Garneau-Tsodikova, Sylvie
2018-02-01
The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activity of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against mammalian cells. The best compounds from our study exhibited broad-spectrum activity against most of the fungal strains tested, with excellent MIC values against a number of clinical isolates. The most promising compounds were found to be less hemolytic than the least hemolytic FDA-approved azole antifungal agent voriconazole (VOR). Finally, we demonstrated that the synthetic alkyl-amino FLC analogues displayed chain-dependent fungal membrane disruption as well as inhibition of ergosterol biosynthesis as possible mechanisms of action. Copyright © 2017 Elsevier Ltd. All rights reserved.
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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
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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.
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Raman, Namrata; Lee, Myung-Ryul
2014-01-01
Candida albicans is the most common fungal pathogen responsible for hospital-acquired infections. Most C albicans infections are associated with the implantation of medical devices that act as points of entry for the pathogen and as substrates for the growth of fungal biofilms that are notoriously difficult to eliminate by systemic administration of conventional antifungal agents. In this study, we report a fill-and-purge approach to the layer-by-layer fabrication of biocompatible, nanoscale ‘polyelectrolyte multilayers’ (PEMs) on the luminal surfaces of flexible catheters, and an investigation of this platform for the localized, intraluminal release of a cationic β-peptide-based antifungal agent. We demonstrate that polyethylene catheter tubes with luminal surfaces coated with multilayers ~700 nm thick fabricated from poly-L-glutamic acid (PGA) and poly-L-lysine (PLL) can be loaded, post-fabrication, by infusion with β-peptide, and that this approach promotes extended intraluminal release of this agent (over ~4 months) when incubated in physiological media. The β-peptide remained potent against intraluminal inoculation of the catheters with C albicans and substantially reduced the formation of C albicans biofilms on the inner surfaces of film-coated catheters. Finally, we report that these β-peptide-loaded coatings exhibit antifungal activity under conditions that simulate intermittent catheter use and microbial challenge for at least three weeks. We conclude that β-peptide-loaded PEMs offer a novel and promising approach to kill C albicans and prevent fungal biofilm formation on surfaces, with the potential to substantially reduce the incidence of device-associated infections in indwelling catheters. β-Peptides comprise a promising new class of antifungal agents that could help address problems associated with the use of conventional antifungal agents. The versatility of the layer-by-layer approach used here thus suggests additional opportunities to exploit these new agents in other biomedical and personal care applications in which fungal infections are endemic. PMID:24862322
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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.
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Chamilos, Georgios; Kontoyiannis, Dimitrios P
2006-08-01
Despite expansion of the antifungal armamentarium over the past decade, the mortality rate for invasive fungal infections remains high in severely immunocompromised patients. Furthermore, in recent years, difficult-to-treat invasive infections caused by rare molds and yeasts have emerged in high-risk patients receiving antifungal prophylaxis or empirical treatment. Antifungal combinations are increasingly used in clinical practice to improve outcomes for refractory mycoses because of the suboptimal efficacy of current antifungal agents. Herein we review recent advances in the area of antifungal combinations in high-risk patients to separate empiricism from evidence-based medicine. Thus far, the benefits of combination antifungal therapy have been difficult to prove for invasive fungal infections other than cryptococcal meningitis. The recent introduction of a new class of antifungal agents (the echinocandins) and extended-spectrum triazoles has rejuvenated interest in studying those combinations for difficult-to-treat aspergillosis, as recent observational studies show promise. In view of the evolving epidemiology of invasive fungal infections, combination antifungal therapy could be most valuable in preemptive management of carefully selected high-risk patients; however, this should be studied in appropriate trials.
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Antifungal resistance in mucorales.
Dannaoui, E
2017-11-01
The order Mucorales, which includes the agents of mucormycosis, comprises a large number of species. These fungi are characterised by high-level resistance to most currently available antifungal drugs. Standardised antifungal susceptibility testing methods are now available, allowing a better understanding of the in vitro activity of antifungal drugs against members of Mucorales. Such tests have made apparent that antifungal susceptibility within this group may be species-specific. Experimental animal models of mucormycosis have also been developed and are of great importance in bridging the gap between in vitro results and clinical trials. Amphotericin B, posaconazole and isavuconazole are currently the most active agents against Mucorales; however, their activity remains suboptimal and new therapeutic strategies are needed. Combination therapy could be a promising approach to overcome resistance, but further studies are required to confirm its benefits and safety for patients. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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Lino, Cleudiomar Inácio; Gonçalves de Souza, Igor; Borelli, Beatriz Martins; Silvério Matos, Thelma Tirone; Santos Teixeira, Iasmin Natália; Ramos, Jonas Pereira; Maria de Souza Fagundes, Elaine; de Oliveira Fernandes, Philipe; Maltarollo, Vinícius Gonçalves; Johann, Susana; de Oliveira, Renata Barbosa
2018-05-10
In the search for new antifungal agents, a novel series of fifteen hydrazine-thiazole derivatives was synthesized and assayed in vitro against six clinically important Candida and Cryptococcus species and Paracoccidioides brasiliensis. Eight compounds showed promising antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.45 to 31.2 μM, some of them being equally or more active than the drug fluconazole and amphotericin B. Active compounds were additionally tested for toxicity against human embryonic kidney (HEK-293) cells and none of them exhibited significant cytotoxicity, indicating high selectivity. Molecular modeling studies results corroborated experimental SAR results, suggesting their use in the design of new antifungal agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Raman, Namrata; Lee, Myung-Ryul; Palecek, Sean P; Lynn, David M
2014-10-10
Candida albicans is the most common fungal pathogen responsible for hospital-acquired infections. Most C. albicans infections are associated with the implantation of medical devices that act as points of entry for the pathogen and as substrates for the growth of fungal biofilms that are notoriously difficult to eliminate by systemic administration of conventional antifungal agents. In this study, we report a fill-and-purge approach to the layer-by-layer fabrication of biocompatible, nanoscale 'polyelectrolyte multilayers' (PEMs) on the luminal surfaces of flexible catheters, and an investigation of this platform for the localized, intraluminal release of a cationic β-peptide-based antifungal agent. We demonstrate that polyethylene catheter tubes with luminal surfaces coated with multilayers ~700nm thick fabricated from poly-l-glutamic acid (PGA) and poly-l-lysine (PLL) can be loaded, post-fabrication, by infusion with β-peptide, and that this approach promotes extended intraluminal release of this agent (over ~4months) when incubated in physiological media. The β-peptide remained potent against intraluminal inoculation of the catheters with C. albicans and substantially reduced the formation of C. albicans biofilms on the inner surfaces of film-coated catheters. Finally, we report that these β-peptide-loaded coatings exhibit antifungal activity under conditions that simulate intermittent catheter use and microbial challenge for at least three weeks. We conclude that β-peptide-loaded PEMs offer a novel and promising approach to kill C. albicans and prevent fungal biofilm formation on surfaces, with the potential to substantially reduce the incidence of device-associated infections in indwelling catheters. β-Peptides comprise a promising new class of antifungal agents that could help address problems associated with the use of conventional antifungal agents. The versatility of the layer-by-layer approach used here thus suggests additional opportunities to exploit these new agents in other biomedical and personal care applications in which fungal infections are endemic. Copyright © 2014 Elsevier B.V. All rights reserved.
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A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens.
Rank, Leslie A; Walsh, Naomi M; Liu, Runhui; Lim, Fang Yun; Bok, Jin Woo; Huang, Mingwei; Keller, Nancy P; Gellman, Samuel H; Hull, Christina M
2017-10-01
Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus , reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus , including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies. Copyright © 2017 American Society for Microbiology.
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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
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Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori
2015-01-01
Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333
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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.
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Antifungal Activity of Commercial Essential Oils and Biocides against Candida Albicans.
Serra, Elisa; Hidalgo-Bastida, Lilia Araida; Verran, Joanna; Williams, David; Malic, Sladjana
2018-01-25
Management of oral candidosis, most frequently caused by Candida albicans , is limited due to the relatively low number of antifungal drugs and the emergence of antifungal tolerance. In this study, the antifungal activity of a range of commercial essential oils, two terpenes, chlorhexidine and triclosan was evaluated against C. albicans in planktonic and biofilm form. In addition, cytotoxicity of the most promising compounds was assessed using murine fibroblasts and expressed as half maximal inhibitory concentrations (IC50). Antifungal activity was determined using a broth microdilution assay. The minimum inhibitory concentration (MIC) was established against planktonic cells cultured in a range of concentrations of the test agents. The minimal biofilm eradication concentration (MBEC) was determined by measuring re-growth of cells after pre-formed biofilm was treated for 24 h with the test agents. All tested commercial essential oils demonstrated anticandidal activity (MICs from 0.06% ( v / v ) to 0.4% ( v / v )) against planktonic cultures, with a noticeable increase in resistance exhibited by biofilms (MBECs > 1.5% ( v / v )). The IC50s of the commercial essential oils were lower than the MICs, while a one hour application of chlorhexidine was not cytotoxic at concentrations lower than the MIC. In conclusion, the tested commercial essential oils exhibit potential as therapeutic agents against C. albicans , although host cell cytotoxicity is a consideration when developing these new treatments.
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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
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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
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Li, Dangdang; Zhang, Shasha; Song, Zehua; Li, Wei; Zhu, Feng; Zhang, Jiwen; Li, Shengkun
2018-01-01
The synthesis of antifungal natural product drimenal was accomplished. Bio-inspired optimization protruded chiral 8-(R)-drimane fused oxazinone D as a lead, considering favorable physicochemical profiles for novel pesticides. The improved scalable synthesis of scaffold D was implemented by Hofmann rearrangment under mild conditions. Detailed structural optimization was discussed for both antifungal and antibacterial exploration. Substituted groups (SGs) with C 3 ∼C 5 hydrocarbon chain are recommended for exploration of antifungal agents, while substituents with C 4 ∼C 6 carbon length are preferred for antibacterial ingredients. The chiral drimane fused oxazinone D8 was selected as a promising antifungal candidate against Botrytis cirerea, with an EC 50 value of 1.18 mg/L, with the enhancement of up to >25 folds and >80 folds than the mother compound D, and acyclic counterpart AB5, respectively. The in vivo bioassay confirmed much better preservative effect of D8 than that of Carbendazim. The chiral oxazinone variant D10 possessed prominent antibacterial activity, with MIC values of 8 mg/L against both Bacillus subtilis and Ralstonia solanacearum, showing advantages over the positive control streptomycin sulfate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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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.
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Antifungal activity of essential oils of Croton species from the Brazilian Caatinga biome.
Fontenelle, R O S; Morais, S M; Brito, E H S; Brilhante, R S N; Cordeiro, R A; Nascimento, N R F; Kerntopf, M R; Sidrim, J J C; Rocha, M F G
2008-05-01
To find new antifungal agents among essential oils from Brazilian Croton species. Plant leaves were steam distilled and the obtained essential oils were analyzed by gas chromatography/mass spectroscopy. The main constituents were estragole and anethole for Croton zehntneri, methyl-eugenol and bicyclogermacrene for Croton nepetaefolius and spathulenol and bicyclogermacrene for Croton argyrophylloides. The antifungal activity of essential oils was evaluated against Candida albicans, Candida tropicalis and Microsporum canis by the agar-well diffusion method and the minimum inhibitory concentration (MIC) by the broth microdilution method. Essential oils of Croton species demonstrated better activity against M. canis. Among the three plants C. argyrophylloides showed the best results, with MIC ranging from 9 to 19 microg ml(-1). The acute administration of the essential oil up to 3 g kg(-1) by the oral route to mice was devoid of overt toxicity. The studied essential oils are active in vitro against the dermatophyte M. canis and present relative lack of acute toxicity in vivo. Because of its antifungal activity and low toxicity, the essential oils of studied Croton species are promising sources for new phytotherapeutic agents to treat dermatophytosis.
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Synthesis and antifungal evaluation of (1,2,3-triazol-4-yl)methyl nicotinate chitosan.
Qin, Yukun; Liu, Song; Xing, Ronge; Li, Kecheng; Yu, Huahua; Li, Pengcheng
2013-10-01
With an aim to discover novel chitosan derivatives with significant activities against crop-threatening fungi, (1,2,3-triazol-4-yl)methyl nicotinate chitosan (TAMNCS) was prepared via azide-alkyne click reaction. Its structure was characterized by FT-IR, (1)H NMR, elemental analysis, DSC, and SEM. In vitro antifungal properties of TAMNCS against Rhizoctonia solani Kühn (R. solani), Stemphylium solani weber (S. solani), and Alternaria porri (A. porri) were studied at the concentrations ranged from 0.25 mg/mL to 1.0 mg/mL. Experiments conducted displayed the derivative had obviously enhanced antifungal activity after chemical modification compared with original chitosan. Moreover, it was shown that TAMNCS can 94.2% inhibit growth of A. porri at 1.0 mg/mL, while dose at which the fungicide triadimefon had lower inhibitory index (62.2%). The primary antifungal results described here indicate this derivative may be a promising candidate as an antifungal agent. Copyright © 2013 Elsevier B.V. All rights reserved.
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Common drug-drug interactions in antifungal treatments for superficial fungal infections.
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.
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Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids
NASA Astrophysics Data System (ADS)
Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.
2011-05-01
In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.
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Holbrook, Selina Y L; Garzan, Atefeh; Dennis, Emily K; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie
2017-10-20
As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles. Exploring combination therapy that involves the current azoles and another drug has been shown to be a promising strategy. Haloperidol and its derivative, bromperidol, were originally discovered as antipsychotics. Herein, we synthesize and report a series of bromperidol derivatives and their synergistic antifungal interactions in combination with a variety of current azole antifungals against a wide panel of fungal pathogens. We further select two representative combinations and confirm the antifungal synergy by performing time-kill assays. Furthermore, we evaluate the ability of selected combinations to destroy fungal biofilm. Finally, we perform mammalian cytotoxicity assays with the representative combinations against three mammalian cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.
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.
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Topical antifungal agents: an update.
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.
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Sedaxicenes: potential new antifungal ferrocene-based agents?
Rubbiani, R; Blacque, O; Gasser, G
2016-04-21
Fungal infections are a group of diseases spread all over the world with an extremely high morbidity. Worryingly, although several pathogenic fungi were found to develop resistance towards traditional therapy, research towards the discovery of novel antimycotic agents is very limited. Considering the promising results obtained with the ferrocene-based drug candidates Ferroquine and Ferrocifen as antimalarial and anticancer drug candidates, respectively, we envisaged derivatizing the organic scaffold of a new broad-spectrum fungicide, namely sedaxane, with a ferrocenyl moiety in order to obtain new metal-based antifungal agents. The new ferrocenyl sedaxane derivatives called herein Sedaxicenes (, and ) were characterized using different analytical techniques and the structures were confirmed by X-ray crystallography. As expected for antimycotic agents, , and were found to have a low or even no toxicity towards human cells (IC50 > 100 μM). Interestingly, while the parent drug did not display any mycotoxicity (EC50 > 100 μM), complex was found to have some antifungal activity with an IC50 value of 43 μM under the same experimental conditions. In order to investigate the possible redox-mediated mode of action of , we synthesized the ruthenocene analogue of , namely . Ruthenocene is known to have a completely different electrochemical behaviour from ferrocene although both the compounds are isostructural. As anticipated, complex was found to induce an increase of the reactive oxygen species level in S. cerevisiae, contrary to its analogue and to the parent compound sedaxane.
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Mnif, Ines; Hammami, Ines; Triki, Mohamed Ali; Azabou, Manel Cheffi; Ellouze-Chaabouni, Semia; Ghribi, Dhouha
2015-11-01
Bacillus subtilis SPB1 lipopeptides were evaluated as a natural antifungal agent against Fusarium solani infestation. In vitro antifungal assay showed a minimal inhibitory concentration of about 3 mg/ml with a fungicidal mode of action. In fact, treatment of F. solani by SPB1 lipopeptides generated excessive lyses of the mycelium and caused polynucleation and destruction of the related spores together with a total inhibition of spore production. Furthermore, an inhibition of germination potency accompanied with a high spore blowing was observed. Moreover, in order to be applied in agricultural field, in vivo antifungal activity was proved against the dry rot potato tubers caused by F. solani. Preventive treatment appeared as the most promising as after 20 days of fungi inoculation, rot invasion was reduced by almost 78%, in comparison to that of non-treated one. When treating infected tomato plants, disease symptoms were reduced by almost 100% when applying the curative method. Results of this study are very promising as it enables the use of the crude lipopeptide preparation of B. subtilis SPB1 as a potent natural fungicide that could effectively control the infection of F. solani in tomato and potato tubers at a concentration similar to the commercial fungicide hymexazol and therefore prevent the damage of olive tree.
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Tissue Penetration of Antifungal Agents
Felton, Timothy; Troke, Peter F.
2014-01-01
SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137
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Plant latex: a promising antifungal agent for post harvest disease control.
Sibi, G; Wadhavan, Rashmi; Singh, Sneha; Shukla, Abhilasha; Dhananjaya, K; Ravikumar, K R; Mallesha, H
2013-12-01
Bioactive compounds from plant latex are potential source of antifungic against post harvest pathogens. Latex from a total of seven plant species was investigated for its phytochemical and antifungal properties. Six fungi namely Aspergillus fumigatus, A. niger, A. terreus, F. solani, P. digitatum and R. arrhizus were isolated from infected fruits and vegetables and tested against various solvent extracts of latex. Analysis of latex extracts with phytochemical tests showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. Antifungal assay revealed the potential inhibitory activity of petroleum ether extracts against the postharvest fungal isolates. Various degree of sensitivity was observed irrespective of plant species studied with A. terreus and P. digitatum as the most susceptible ones. F. solani and A. fumigatus were moderately sensitive to the latex extracts tested. Among the plants, latex of Thevetia peruviana (75.2%) and Artocarpus heterophyllus (64.8%) were having potential antifungal activity against the isolates followed by Manilkara zapota (51.1%). In conclusion, use of plant latex makes interest to control postharvest fungal diseases and is fitting well with the concept of safety for human health and environment.
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Antifungal activity of Zuccagnia punctata Cav.: evidence for the mechanism of action.
Svetaz, Laura; Agüero, María Belén; Alvarez, Sandra; Luna, Lorena; Feresin, Gabriela; Derita, Marcos; Tapia, Alejandro; Zacchino, Susana
2007-08-01
Petroleum ether and dichloromethane extracts of fruits, aerial parts and exudate of Zuccagnia punctata Cav. (Fabaceae) showed moderate antifungal activities against the yeasts C. albicans, S. cerevisiae and C. neoformans (MICs: 62.5 - 250 microg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 microg/mL) thus supporting the ethnopharmacological use of this plant. Antifungal activity-directed fractionation of active extracts by using bioautography led to the isolation of 2',4'-dihydroxy-3'-methoxychalcone (1) and 2',4'-dihydroxychalcone (2) as the compounds responsible for the antifungal activity. Second-order studies included MIC (80), MIC (50) and MFC of both chalcones in an extended panel of clinical isolates of the most sensitive fungi, and also comprised a series of targeted assays. They showed that the most active chalcone 2 is fungicidal rather than fungistatic, does not disrupt the fungal membranes up to 4 x MFC and does not act by inhibiting the fungal cell wall. So, 2',4'-dihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, and thus appears to be very promising as a novel antifungal agent.
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Pace, Jennifer R; DeBerardinis, Albert M; Sail, Vibhavari; Tacheva-Grigorova, Silvia K; Chan, Kelly A; Tran, Raymond; Raccuia, Daniel S; Wechsler-Reya, Robert J; Hadden, M Kyle
2016-04-28
Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.
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Trehalose pathway as an antifungal target.
Perfect, John R; Tenor, Jennifer L; Miao, Yi; Brennan, Richard G
2017-02-17
With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with widespread use of antifungal agents, drug-resistant fungal infections are on the rise. Therefore, there is some urgency to develop the antifungal pipeline with the goal of new antifungal agent discovery. In this review, a simple metabolic pathway, which forms the disaccharide, trehalose, will be characterized and its potential as a focus for antifungal target(s) explained. It possesses several important features for development of antifungal agents. First, it appears to have fungicidal characteristics and second, it is broad spectrum with importance across both ascomycete and basidiomycete species. Finally, this pathway is not found in mammals so theoretically specific inhibitors of the trehalose pathway and its enzymes in fungi should be relatively non-toxic for mammals. The trehalose pathway and its critical enzymes are now in a position to have directed antifungal discovery initiated in order to find a new class of antifungal drugs.
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Chemosensitization as a Means to Augment Commercial Antifungal Agents
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
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USDA-ARS?s Scientific Manuscript database
Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...
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Antifungal and Ichthyotoxic Sesquiterpenoids from Santalum album Heartwood.
Kim, Tae Hoon; Hatano, Tsutomu; Okamoto, Keinosuke; Yoshida, Takashi; Kanzaki, Hiroshi; Arita, Michiko; Ito, Hideyuki
2017-07-08
In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n -hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum . Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections.
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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.
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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.
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Emerging Drugs and Vaccines for Candidemia
Moriyama, Brad; Gordon, Lori A.; McCarthy, Matthew; Henning, Stacey A.; Walsh, Thomas J.; Penzak, Scott R.
2014-01-01
Summary Candidemia and other forms of invasive candidiasis are important causes of morbidity and mortality. The evolving challenge of antimicrobial resistance among fungal pathogens continues to highlight the need for potent, new antifungal agents. MEDLINE, EMBASE, Scopus, and Web of Science searches (up to January 2014) of the English-language literature were performed with the keywords “Candida” or “Candidemia” or “Candidiasis” and terms describing investigational drugs with activity against Candida spp. Conference abstracts and the bibliographies of pertinent articles were also reviewed for relevant reports. ClinicalTrials.gov was searched for relevant clinical trials. Currently available antifungal agents for the treatment of candidemia are summarized. Investigational antifungal agents with potential activity against Candida bloodstream infections and other forms of invasive candidiasis and vaccines for prevention of Candida infections are also reviewed as are selected antifungal agents no longer in development. Antifungal agents currently in clinical trials include isavuconazole, albaconazole, SCY-078, VT-1161, and T-2307. Further data are needed to determine the role of these compounds in the treatment of candidemia and other forms of invasive candidiasis. The progressive reduction in antimicrobial drug development may result in a decline in antifungal drug discovery. Still there remains a critical need for new antifungal agents to treat and prevent invasive candidiasis and other life-threatening mycoses. PMID:25294098
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[In vitro activity of voriconazole and three other antifungal agents against dermatophytes].
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.
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Blundell, Ross D; Williams, Simon J; Arras, Samantha D M; Chitty, Jessica L; Blake, Kirsten L; Ericsson, Daniel J; Tibrewal, Nidhi; Rohr, Jurgen; Koh, Y Q Andre E; Kappler, Ulrike; Robertson, Avril A B; Butler, Mark S; Cooper, Matthew A; Kobe, Bostjan; Fraser, James A
2016-09-09
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C. neoformans, as well as complete loss of virulence in a murine model. Cryptococcal AdSS was expressed and purified in Escherichia coli and the enzyme's crystal structure determined, the first example of a structure of this enzyme from fungi. Together with enzyme kinetic studies, this structural information enabled comparison of the fungal enzyme with the human orthologue and revealed species-specific differences potentially exploitable via rational drug design. These results validate AdSS as a promising antifungal drug target and lay a foundation for future in silico and in vitro screens for novel antifungal compounds.
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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
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Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís
2014-06-02
Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums. Copyright © 2014 Elsevier B.V. All rights reserved.
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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
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Drugs currently under investigation for the treatment of invasive candidiasis.
McCarthy, Matthew W; Walsh, Thomas J
2017-07-01
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.
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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.
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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
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Candidiasis and the impact of flow cytometry on antifungal drug discovery.
Ku, Tsun Sheng N; Bernardo, Stella; Walraven, Carla J; Lee, Samuel A
2017-11-01
Invasive candidiasis continues to be associated with significant morbidity and mortality as well as substantial health care costs nationally and globally. One of the contributing factors is the development of resistance to antifungal agents that are already in clinical use. Moreover, there are known treatment limitations with all of the available antifungal agents. Since traditional techniques in novel drug discovery are time consuming, high-throughput screening using flow cytometry presents as a potential tool to identify new antifungal agents that would be useful in the management of these patients. Areas covered: In this review, the authors discuss the use of automated high-throughput screening assays based upon flow cytometry to identify potential antifungals from a library comprised of a large number of bioactive compounds. They also review studies that employed the use of this research methodology that has identified compounds with antifungal activity. Expert opinion: High-throughput screening using flow cytometry has substantially decreased the processing time necessary for screening thousands of compounds, and has helped enhance our understanding of fungal pathogenesis. Indeed, the authors see this technology as a powerful tool to help scientists identify new antifungal agents that can be added to the clinician's arsenal in their fight against invasive candidiasis.
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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.
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Szymańska, Emilia; Winnicka, Katarzyna; Wieczorek, Piotr; Sacha, Paweł Tomasz; Tryniszewska, Elżbieta Anna
2014-01-01
The combination of an antifungal agent and drug carrier with adjunctive antimicrobial properties represents novel strategy of complex therapy in pharmaceutical technology. The goal of this study was to investigate the unmodified and ion cross-linked chitosan’s influence on anti-Candida activity of clotrimazole used as a model drug in hydrogels. It was particularly crucial to explore whether the chitosans’ structure modification by β-glycerophosphate altered its antifungal properties. Antifungal studies (performed by plate diffusion method according to CLSI reference protocol) revealed that hydrogels obtained with chitosan/β-glycerophosphate displayed lower anti-Candida effect, probably as a result of weakened polycationic properties of chitosan in the presence of ion cross-linker. Designed chitosan hydrogels with clotrimazole were found to be more efficient against tested Candida strains and showed more favorable drug release profile compared to commercially available product. These observations indicate that novel chitosan formulations may be considered as promising semi-solid delivery system of clotrimazole. PMID:25272230
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Szymańska, Emilia; Winnicka, Katarzyna; Wieczorek, Piotr; Sacha, Paweł Tomasz; Tryniszewska, Elżbieta Anna
2014-09-30
The combination of an antifungal agent and drug carrier with adjunctive antimicrobial properties represents novel strategy of complex therapy in pharmaceutical technology. The goal of this study was to investigate the unmodified and ion cross-linked chitosan's influence on anti-Candida activity of clotrimazole used as a model drug in hydrogels. It was particularly crucial to explore whether the chitosans' structure modification by β-glycerophosphate altered its antifungal properties. Antifungal studies (performed by plate diffusion method according to CLSI reference protocol) revealed that hydrogels obtained with chitosan/β-glycerophosphate displayed lower anti-Candida effect, probably as a result of weakened polycationic properties of chitosan in the presence of ion cross-linker. Designed chitosan hydrogels with clotrimazole were found to be more efficient against tested Candida strains and showed more favorable drug release profile compared to commercially available product. These observations indicate that novel chitosan formulations may be considered as promising semi-solid delivery system of clotrimazole.
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Fondevilla, Esther; Grau, Santiago; Mojal, Sergi; Palomar, Mercedes; Matas, Lurdes; Gudiol, Francesc
2016-01-01
Objective To know the patterns and consumption trends (2008-2013) of antifungal agents for systemic use in 52 acute care hospitals affiliated to VINCat Program in Catalonia (Spain). Methods Consumption was calculated in defined daily doses (DDD)/100 patient-days and analyzed according to hospital size and complexity and clinical departments. Results Antifungal consumption was higher in intensive care units (ICU) (14.79) than in medical (3.08) and surgical departments (1.19). Fluconazole was the most consumed agent in all type of hospitals and departments. Overall antifungal consumption increased by 20.5%during the study period (p = 0.066); a significant upward trend was observed in the consumption of both azoles and echinocandins. In ICUs, antifungal consumption increased by 12.4% (p = 0.019). Conclusions The study showed a sustained increase in the overall consumption of systemic antifungals in a large number of acute care hospitals of different characteristics in Catalonia. In ICUs there was a trend towards the substitution of older agents by the new ones.
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Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.
Homa, Mónika; Fekete, Ildikó Pálma; Böszörményi, Andrea; Singh, Yendrembam Randhir Babu; Selvam, Kanesan Panneer; Shobana, Coimbatore Subramanian; Manikandan, Palanisamy; Kredics, László; Vágvölgyi, Csaba; Galgóczy, László
2015-09-01
The present study was carried out to investigate the antifungal effects of Cinnamomum zeylanicum, Citrus limon, Juniperus communis, Eucalyptus citriodora, Gaultheria procumbens, Melaleuca alternifolia, Origanum majorana, Salvia sclarea, and Thymus vulgaris essential oils against Fusarium species, the most common etiologic agents of filamentous fungal keratitis in South India. C. zeylanicum essential oil showed strong anti-Fusarium activity, whereas all the other tested essential oils proved to be less effective. The main component of C. zeylanicum essential oil, trans-cinnamaldehyde, was also tested and showed a similar effect as the oil. The in vitro interaction between trans-cinnamaldehyde and natamycin, the first-line therapeutic agent of Fusarium keratitis, was also investigated; an enhanced fungal growth inhibition was observed when these agents were applied in combination. Light and fluorescent microscopic observations revealed that C. zeylanicum essential oil/trans-cinnamaldehyde reduces the cellular metabolism and inhibits the conidia germination. Furthermore, necrotic events were significantly more frequent in the presence of these two compounds. According to our results, C. zeylanicum essential oil/trans-cinnamaldehyde provides a promising basis to develop a novel strategy for the treatment of Fusarium keratitis. Georg Thieme Verlag KG Stuttgart · New York.
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Chen, Ying-Lien; Lehman, Virginia N; Averette, Anna F; Perfect, John R; Heitman, Joseph
2013-01-01
The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.
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Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans.
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.
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3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans.
Dyląg, Mariusz; Lis, Paweł; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław
2013-05-03
We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug. Copyright © 2013 Elsevier Inc. All rights reserved.
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Gao, Mei; Wang, Hui; Zhu, LiJuan
2016-01-01
Vulvovaginal candidiasis (VVC) is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ). Quercetin (QCT) is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm. 17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm. We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i) be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii) inhibit fungal adherence, cell surface hydrophobicity (CSH), flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii) down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv) the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ. Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm. © 2016 The Author(s) Published by S. Karger AG, Basel.
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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.
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In Vitro Activity of E1210, a Novel Antifungal, against Clinically Important Yeasts and Molds▿
Miyazaki, Mamiko; Horii, Takaaki; Hata, Katsura; Watanabe, Nao-aki; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto
2011-01-01
E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC90 of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC90 of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections. PMID:21825291
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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.
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Antifungal stewardship considerations for adults and pediatrics.
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.
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Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.
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.
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Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans
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
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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.
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The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose.
Elias, Luciana M; Fortkamp, Diana; Sartori, Sérgio B; Ferreira, Marília C; Gomes, Luiz H; Azevedo, João L; Montoya, Quimi V; Rodrigues, André; Ferreira, Antonio G; Lira, Simone P
2018-03-31
Anthracnose is a crop disease usually caused by fungi in the genus Colletotrichum or Gloeosporium. These are considered one of the main pathogens, causing significant economic losses, such as in peppers and guarana. The current forms of control include the use of resistant cultivars, sanitary pruning and fungicides. However, even with the use of some methods of controlling these cultures, the crops are not free of anthracnose. Additionally, excessive application of fungicides increases the resistance of pathogens to agrochemicals and cause harm to human health and the environment. In order to find natural antifungal agents against guarana anthracnose, endophytic fungi were isolated from Amazon guarana. The compounds piliformic acid and cytochalasin D were isolated by chromatographic techniques from two Xylaria spp., guided by assays with Colletotrichum gloeosporioides. The isolated compounds were identified by spectrometric techniques, as NMR and mass spectrometry. This is the first report that piliformic acid and cytochalasin D have antifungal activity against C. gloeosporioides with MIC 2.92 and 2.46μmolmL -1 respectively. Captan and difenoconazole were included as positive controls (MIC 16.63 and 0.02μmolmL -1 , respectively). Thus, Xylaria species presented a biotechnological potential and production of different active compounds which might be promising against anthracnose disease. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.
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Determining Antifungal Target Sites in the Sterol Pathway of the Yeast Candida and Saccharomyces
1997-10-01
interaction of the azole antifungal agent SCH39304 with the cytochrome P-450 monooxygenase system isolated from Cryptococcus neoformans. Antimicrob. Agents...isolates of Cryptococcus neoformans. Antimicrob. Agents Chemother. 41: 748-751. 16. Wheat, J., Marichal, P., Vanden Bossche, H., Le Monte, A., and
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Tyczkowska-Sieron, E; Markiewicz, J; Grzesiak, B; Krukowski, H; Glowacka, A; Tyczkowski, J
2018-01-01
Mastitis is a serious bovine diseases that can be caused by Prototheca zopfii, yeast-like algae belonging to the family Chlorellaceae. The substantial economic losses and health damage associated with bovine mastitis emphasize the need to develop effective strategies aimed at control of the infection. Unfortunately, P. zopfii is highly resistant to most common antibacterial and antifungal agents, as well as to heat treatment. We report here the first attempt to use cold atmospheric plasma to inactivate this pathogen. We studied 20 strains of P. zopfii isolated from milk samples taken from cows with clinical or subclinical mastitis. The studies confirmed the high level of resistance of P. zopfii to typical antifungal agents, such as voriconazole, fluconazole, amphotericin B, caspofungin, anidulafungin, and micafungin. In contrast, each of the strains revealed high susceptibility to cold atmospheric plasma, >2-fold higher compared with a reference strain of Candida albicans. The obtained results are promising and open up a new approach in the fight against P. zopfii. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
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Onozawa, Kyoko; Miyake, Noriko; Iwasaki, Noriko; Nishida, Ruriko; Chong, Yong; Shimoda, Shinji; Shimono, Nobuyuki; Akashi, Koichi
2015-09-01
Fungus balls have been rarely implicated as a cause of urinary tract obstruction. Here, we report a case of Candida albicans fungus balls in the urinary tract after the treatment of Candida endophthalmitis that has enough periods and adequate amount of antifungal agents. The patient completely recovered from this rare complication by irrigating through single-J stent and changing antifungal agents. Here we emphasize that we should take into account not only the susceptibility test results but also the difference in excretion route and tissue distribution of antifungal agents. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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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.
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USDA-ARS?s Scientific Manuscript database
Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis, by addition of a methyl, methoxyl or a chloro group at position 4 of the aromatic ri...
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Denardi, Laura Bedin; Mario, Débora Alves Nunes; Loreto, Érico Silva; Santurio, Janio Morais; Alves, Sydney Hartz
2015-03-01
In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata , a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro , notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.
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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.
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Label-free imaging of fatty acid content within yeast samples
NASA Astrophysics Data System (ADS)
Garrett, N.; Moger, J.
2013-02-01
Fungi have been found to be an underlying cause of 70% of all plant and animal extinctions caused by infectious diseases. Fungal infections are a growing problem affecting global health, food production and ecosystems. Lipid metabolism is a promising target for antifungal drugs and since effective treatment of fungal infections requires a better understanding of the effects of antifungal agents at the cellular level, new techniques are needed to investigate this problem. Recent advances in nonlinear microscopy allow chemically-specific contrast to be obtained non-invasively from intrinsic chemical bonds within live samples using advanced spectroscopy techniques probing Raman-active resonances. We present preliminary data using Stimulated Raman Scattering (SRS) microscopy as a means to visualise lipid droplets within individual living fungi by probing Raman resonances of the CH stretching region between 2825cm-1 and 3030cm-1.
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Anti-Candida albicans natural products, sources of new antifungal drugs: A review.
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.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.
ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole,more » ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatuspotency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent.« less
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Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando
2017-01-01
ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus Aspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatus CYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis of A. fumigatus CYP51/voriconazole and Candida albicans CYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using two A. fumigatus strains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatus potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent. PMID:28461309
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Stenbæk, Jonas; Löf, David; Falkman, Peter; Jensen, Bo; Cárdenas, Marité
2017-07-01
The potential of a lactylate (the sodium caproyl lactylate or C10 lactylate), a typical food grade emulsifier, as an anionic environmental friendly anti-fungal additive was tested in growth medium and formulated in a protective coating for exterior wood. Different laboratory growth tests on the blue stain fungus Aureobasidium pullulans were performed and its interactions on a model fungal cell membrane were studied. Promising short term anti-fungal effects in growth tests were observed, although significant but less dramatic effects took place in coating test on wood panels. Scanning electron microscope analysis shows clear differences in the amount of fungal slime on the mycelium of Aureobasidium pullulans when the fungus was exposed of C10 lactylate. This could indicate an effect on the pullulan and melanin production by the fungus. Moreover, the interaction studies on model fungal cell membranes show that C10 lactylate affects the phospholipid bilayer in a similar manner to other negative charged detergents. Copyright © 2017 Elsevier Inc. All rights reserved.
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Keratitis-associated fungi form biofilms with reduced antifungal drug susceptibility.
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.
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Tian, Jun; Wang, Yanzhen; Zeng, Hong; Li, Zongyun; Zhang, Peng; Tessema, Akalate; Peng, Xue
2015-06-02
A variety of plant products have been recognized for their antifungal activity and recently have attracted food industry attention for their efficacy in controlling postharvest fungal decay of fruits. The antifungal activity of perillaldehyde (PAE) was evaluated against Aspergillus niger, a known cause of grape spoilage, and possible mechanisms were explored. PAE showed notable antifungal activity against A. niger, with a minimum inhibitory concentration (MIC) and a minimum fungicidal concentration (MFC) of 0.25 and 1 μl/ml, respectively. The accumulation of mycelial biomass was also inhibited by PAE in a dose-dependent manner, completely inhibiting mycelial growth at 1 μl/ml. In vivo data confirmed that the vapour treatment of grapes with various concentrations of PAE markedly improved control of A. niger and suppressed natural decay. Concentrations of PAE of 0.075 μl/ml air showed the greatest inhibition of fungal growth compared to the controls. Further experiments indicated that PAE activated a membrane-active mechanism that inhibits ergosterol synthesis, increases membrane permeability (as evidenced by extracellular pH and conductivity measurements), and disrupts membrane integrity, leading to cell death. Our findings suggest that this membrane-active mechanism makes PAE a promising potential antifungal agent for postharvest control of grape spoilage. Copyright © 2015 Elsevier B.V. All rights reserved.
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The antifungal action of dandruff shampoos.
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.
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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...
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Manfredi, M; McCullough, M J; Polonelli, L; Conti, S; Al-Karaawi, Z M; Vescovi, P; Porter, S R
2006-06-01
The most common antifungal drugs in current clinical use for the treatment of oral candidosis are polyenes and azoles, mainly used topically. Poor glycaemic control in association with other local factors, such as the presence of oral dental prostheses, salivary pH, salivary flow rate and tobacco habits, may lead to the development of oral candidosis. Topical antifungal agents are frequently used to prevent the development of candidal infections in patients with poor metabolic control, particularly in the elderly wearing dentures. The aim of this study was to assess the antifungal susceptibility of Candida isolates to six antifungal agents using a commercially available kit, Fungitest. The isolated were collected from patients affected by diabetes mellitus from two different geographic localities (London, UK, and Parma, Italy) and from a group of healthy non-diabetic subjects. No differences in antifungal susceptibility to the six agents tested were observed between Candida isolates from diabetic and non-diabetic subjects. However, differences were observed between the two geographically different diabetes mellitus populations. Oral yeast isolates from diabetes mellitus patients in the UK more often displayed resistance or intermediate resistance to fluconazole (P=0.02), miconazole (P<0.0001), and ketoconazole (P=0.01) than did isolates from diabetes mellitus patients in Italy. In addition, more C. albicans isolates were found in diabetic and non-diabetic subjects that were susceptible to fluconazole (P=0.0008 and P=0.01, respectively) than non-albicans isolates. The difference in the antifungal resistance of isolates from the two populations of diabetes mellitus patients may be related to differences in the therapeutic management of candidal infections between the two centres.
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Simple fluorescence-based high throughput cell viability assay for filamentous fungi.
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.
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Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; Amaral, André Correa; Paccez, Juliano Domiraci; Borges, Clayton Luiz
2017-01-01
Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs. PMID:28694566
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Enhancement of commercial antifungal agents by kojic acid
USDA-ARS?s Scientific Manuscript database
Kojic acid (KA), a natural by-product of fungal fermentation, is a commonly used food and cosmetic additive. We show that KA increases activity of amphotericin B and strobilurin, medical and agricultural antifungal agents, respectively, possibly targeting the fungal antioxidative system. KA shows pr...
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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.
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Fungal infections in burns: a comprehensive review
Struck, M.F.; Gille, J.
2013-01-01
Summary Burn wound infections remain the most important factor limiting survival in burn intensive care units. Large wound surface, impaired immune systems, and broad-spectrum antibiotic therapy contribute to the growth of opportunistic fungal species. Faced with challenging fluid resuscitation, wound excision and cardiopulmonary stabilization, mycosis in burns are likely to be underestimated. Diagnostic performance can sometimes be delayed because clinical signs are unspecific and differentiation between colonization and infection is difficult. Therapeutic measures range from infection prophylaxis over treatment with antifungal agents towards radical amputation of infected limbs. New methods of early and reliable detection of fungal organisms, as well as the use of novel antifungal substances, are promising but require wider establishment to confirm the beneficial effects in burn patients. This review aims to highlight the main important aspects of fungal infections in burns including incidence, infection control, diagnostic and therapeutic approaches, prognosis and outcomes. PMID:24563641
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In Vitro Antimicrobial and Modulatory Activity of the Natural Products Silymarin and Silibinin
Rakelly de Oliveira, Dayanne; Relison Tintino, Saulo; Morais Braga, Maria Flaviana Bezerra; Boligon, Aline Augusti; Linde Athayde, Margareth; Douglas Melo Coutinho, Henrique; de Menezes, Irwin Rose Alencar; Fachinetto, Roselei
2015-01-01
Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line. PMID:25866771
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The Antifungal Activity of Functionalized Chitin Nanocrystals in Poly (Lactid Acid) Films
Salaberria, Asier M.; H. Diaz, Rene; Andrés, María A.; Fernandes, Susana C.M.; Labidi, Jalel
2017-01-01
As, in the market, poly (lactic acid) (PLA) is the most used polymer as an alternative to conventional plastics, and as functionalized chitin nanocrystals (CHNC) can provide structural and bioactive properties, their combination sounds promising in the preparation of functional nanocomposite films for sustainable packaging. Chitin nanocrystals were successfully modified via acylation using anhydride acetic and dodecanoyl chloride acid to improve their compatibility with the matrix, PLA. The nanocomposite films were prepared by extrusion/compression approach using different concentrations of both sets of functionalized CHNC. This investigation brings forward that both sets of modified CHNC act as functional agents, i.e., they slightly improved the hydrophobic character of the PLA nanocomposite films, and, very importantly, they also enhanced their antifungal activity. Nonetheless, the nanocomposite films prepared with the CHNC modified with dodecanoyl chloride acid presented the best properties. PMID:28772902
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Troskie, Anscha Mari; Rautenbach, Marina; Delattin, Nicolas; Vosloo, Johan Arnold; Dathe, Margitta; Thevissen, Karin
2014-01-01
Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low-micromolar range. These tyrocidines also prevented C. albicans biofilm formation in vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment. PMID:24752256
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In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections
Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera
2014-01-01
Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737
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Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.
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.
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NASA Astrophysics Data System (ADS)
Garrett, Natalie L.; Singh, Bhumika; Jones, Andrew; Moger, Julian
2017-06-01
Treatment of dandruff condition usually involves use of antidandruff shampoos containing antifungal agents. Different antifungal agents show variable clinical efficacy based on their cutaneous distribution and bioavailability. Using stimulated Raman scattering (SRS), we mapped the distribution of unlabeled low-molecular weight antifungal compounds zinc pyrithione (ZnPT) and climbazole (CBZ) on the surface of intact porcine skin with cellular precision. SRS has sufficient chemical selectivity and sensitivity to detect the agents on the skin surface based on their unique chemical motifs that do not occur naturally in biological tissues. Moreover, SRS is able to correlate the distribution of the agents with the morphological features of the skin using the CH2 stretch mode, which is abundant in skin lipids. This is a significant strength of the technique since it allows the microscopic accumulation of the agents to be correlated with physiological features and their chemical environment without the use of counter stains. Our findings show that due to its lower solubility, ZnPT coats the surface of the skin with a sparse layer of crystals in the size range of 1 to 4 μm. This is consistent with the current understanding of the mode of action of ZnPT. In contrast, CBZ being more soluble and hydrophobic resulted in diffuse homogeneous distribution. It predominantly resided in microscopic lipid-rich crevasses and penetrated up to 60 μm into the infundibular spaces surrounding the hair shaft. The ability of the SRS to selectively map the distribution of agents on the skin's surface has the potential to provide insight into the mechanisms underpinning the topical application of antifungal or skin-active agents that could lead to the rational engineering of enhanced formulations.
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Hu, Yongxuan; Huang, Xiaowen; Lu, Sha; Hamblin, Michael R.; Mylonakis, Eleftherios; Zhang, Junmin
2014-01-01
Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis. PMID:25366276
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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.
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Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.
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.
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Li, Ding; Luong, Tuong Thi Mai; Dan, Wen-Jia; Ren, Yanliang; Nien, Hoang Xuan; Zhang, An-Ling; Gao, Jin-Ming
2018-01-15
Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by 1 H, 13 C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity. On the other hand, for the first time, these compounds were also assayed as potential inhibitors against Class II fructose-1,6-bisphosphate aldolase (Fba) from the rice blast fungus, Magnaporthe grisea. Compounds 5e and 5g were found to exhibit the inhibition constants (Ki) for 15.12 and 14.27 μM, respectively, as the strongest competitive inhibitors against Fba activity. The possible binding-modes of compounds 5e and 5g were further analyzed by molecular docking algorithms. The results strongly suggested that compound 5g could be a promising lead for the discovery of new fungicides via targeting Class II Fba. Copyright © 2017 Elsevier Ltd. All rights reserved.
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The In Vitro Efficacy of Essential Oils and Antifungal Drugs Against Prototheca zopfii.
Grzesiak, Barbara; Głowacka, Anna; Krukowski, Henryk; Lisowski, Andrzej; Lassa, Henryka; Sienkiewicz, Monika
2016-08-01
The algae of the genus Prototheca are environmental pathogens whose main reservoir is the habitat of cows. They can cause protothecosis in domestic and wild animals, as well as human beings, with the main etiological agents being Prototheca zopfii in animals and Prototheca wickerhamii in humans. The aim of the study was to evaluate the in vitro activity of selected essential oils and antifungal antibiotics against P. zopfii isolates. The material consisted of nine P. zopfii strains isolated from the milk of cows suffering from mastitis. Eight essential oils produced by POLLENA-AROMA, Poland, and nine antifungal agents were tested. The effects of essential oils on P. zopfii were evaluated by microdilution with liquid Sabouraud dextrose broth, and susceptibility to antifungal agents was tested using the disk-diffusion method. All used essential oils inhibited the activity of P. zopfii isolates, with MIC values ranging from 0.2 to 10.5 μl/ml. Cinnamon, clove, and thyme demonstrated the highest activity against the tested P. zopfii strains at concentrations ranging from 0.6 to 1.0 μl/ml. Of the antifungal agents, the tested strains were the most sensitive to nystatin (100 %). The tested essential oils can be used to complement protothecosis therapy in animals and human beings.
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Exploring the molecular basis of antifungal synergies using genome-wide approaches
USDA-ARS?s Scientific Manuscript database
This is a review article summarizing genomic profiling strategies for determining the mechanism of action of antifungal synergies, and highlighting the potential applications of these technologies. Given the limitations of currently available antifungal agents and the development of drug resistance...
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Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.
Pfaller, Michael A; Castanheira, Mariana
2016-01-01
Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis. © 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.
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Sen, Suparna; Borah, Siddhartha Narayan; Bora, Arijit; Deka, Suresh
2017-05-30
Sophorolipids are one of the most promising glycolipid biosurfactants and have been successfully employed in bioremediation and various other industrial sectors. They have also been described to exhibit antimicrobial activity against different bacterial species. Nevertheless, previous literature pertaining to the antifungal activity of sophorolipids are limited indicating the need for further research to explore novel strains with wide antimicrobial activity. A novel yeast strain, Rhodotorula babjevae YS3, was recently isolated from an agricultural field in Assam, Northeast India. This study was primarily emphasized at the characterization and subsequent evaluation of antifungal activity of the sophorolipid biosurfactant produced by R. babjevae YS3. The growth kinetics and biosurfactant production by R. babjevae YS3 was evaluated by cultivation in Bushnell-Haas medium containing glucose (10% w/v) as the sole carbon source. A reduction in the surface tension of the culture medium from 70 to 32.6 mN/m was observed after 24 h. The yield of crude biosurfactant was recorded to be 19.0 g/l which might further increase after optimization of the growth parameters. The biosurfactant was characterized to be a heterogeneous sophorolipid (SL) with both lactonic and acidic forms after TLC, FTIR and LC-MS analyses. The SL exhibited excellent oil spreading and emulsifying activity against crude oil at 38.46 mm 2 and 100% respectively. The CMC was observed to be 130 mg/l. The stability of the SL was evaluated over a wide range of pH (2-10), salinity (2-10% NaCl) and temperature (at 120 °C for time intervals of 30 up to 120 min). The SL was found to retain surface-active properties under the extreme conditions. Additionally, the SL exhibited promising antifungal activity against a considerably broad group of pathogenic fungi viz. Colletotrichum gloeosporioides, Fusarium verticilliodes, Fusarium oxysporum f. sp. pisi, Corynespora cassiicola, and Trichophyton rubrum. The study reports, for the first time, the biosurfactant producing ability of R. babjevae, a relatively lesser studied yeast. The persistent surface active properties of the sophorolipid in extreme conditions advocates its applicability in diverse environmental and industrial sectors. Further, antifungal activities against plant and human pathogens opens up possibilities for development of efficient and eco-friendly antifungal agents with agricultural and biomedical applications.
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Pereira, Fillipe de Oliveira; Mendes, Juliana Moura; Lima, Igara Oliveira; Mota, Kelly Samara de Lira; Oliveira, Wylly Araújo de; Lima, Edeltrudes de Oliveira
2015-02-01
Trichophyton rubrum is the most common fungus causing chronic dermatophytosis in humans. Antifungal activity of promising agents is of great interest. Geraniol and citronellol are monoterpenes with antimicrobial properties. This study aimed to investigate the inhibitory effects and possible mechanism of antifungal activity of geraniol and citronellol against strains of T. rubrum. The minimum inhibitory concentration (MIC) of each drug against 14 strains was determined by broth microdilution. The effects of the drugs on dry mycelial weight, conidial germination, infectivity on human nail fragments, and morphogenesis of T. rubrum were analyzed. The effects on the cell wall (test with sorbitol) and cell membrane (release of intracellular material and ergosterol biosynthesis) were investigated. MIC values of geraniol ranged between 16 and 256 µg/mL while citronellol showed MIC values from 8 to 1024 µg/mL. The drugs (MIC and 2 × MIC) inhibited the mycelial growth, conidia germination, and fungal growth on nail fragments. The drugs (half of MIC) induced the formation of wide, short, and crooked hyphae in T. rubrum morphology. With sorbitol, geraniol MIC was increased by 64-fold and citronellol by 32-fold. The drugs caused leakage of intracellular material and inhibited ergosterol biosynthesis. The results suggest that the drugs damage cell wall and cell membrane of T. rubrum through a mechanism that seems to involve the inhibition of the ergosterol biosynthesis. This study confirms that geraniol and citronellol can be regarded as potential drugs for controlling T. rubrum growth, with great potential against agents of dermatophytosis.
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Gowri, Meiyazhagan; Sofi Beaula, Winfred; Biswal, Jayashree; Dhamodharan, Prabhu; Saiharish, Raghavan; Rohan prasad, Surabi; Pitani, Ravishankar; Kandaswamy, Deivanayagam; Raghunathan, Ragavachary; Jeyakanthan, Jeyaraman; Rayala, Suresh K; Venkatraman, Ganesh
2016-04-01
Further quest for new anti-fungal compounds with proven mechanisms of action arises due to resistance and dose limiting toxicity of existing agents. Among the human fungal pathogens C. albicans predominate by infecting several sites in the body and in particular oral cavity and root canals of human tooth. In the present study, we screened a library of β-lactam substituted polycyclic fused pyrrolidine/pyrrolizidine compounds against Candida sp. Detailed molecular studies were carried out with the active compound 3 on C. albicans. Morphological damage and antibiofilm activity of compound 3 on C. albicans was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. In silico docking studies were carried out to elucidate the mechanism of action of compound 3. Further, the antifungal activity of compound 3 was evaluated in an ex vivo dentinal tubule infection model. Screening data showed that several new compounds were active against Candida sp. Among them, Compound 3 was most potent and exerted time kill effect at 4h, post antifungal effect up to 6h. When used in combination with fluconazole or nystatin, compound 3 revealed an minimum inhibitory concentration (MIC) decrease by 4 fold for both drugs used. In-depth molecular studies with compound 3 on C. albicans showed that this compound inhibited yeast to hyphae (Y-H) conversion and this involved the cAMP pathway. Further, SEM images of C. albicans showed that compound 3 caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, in silico studies revealed that compound 3 docks with the active site of the key enzyme 14-α-demethylase and this might inhibit ergosterol synthesis. In support of this, ergosterol levels were found to be decreased by 32 fold in compound 3 treated samples as analyzed by high performance liquid chromatography (HPLC). Further, the antifungal activity of compound 3 was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed 83% eradication of C. albicans and a 6 log reduction in colony forming unit (CFU) after 24h treatment in the infected tooth samples in this model. Compound 3 was found to be very effective in eradicating C. albicans by inhibiting cAMP pathway and ergosterol biosynthesis. The results of this study can pave the way for developing new antifungal agents with well deciphered mechanisms of action and can be a promising antifungal agent or medicament against root canal infection. Copyright © 2015 Elsevier B.V. All rights reserved.
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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.
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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.
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Jackson, S T; Mullings, A M; Rainford, L; Miller, A
2005-06-01
Data in the Caribbean documenting the speciation of yeast associated with vulvovaginitis are lacking. The widespread use of antibiotics and increased availability of antimycotic agents, both prescribed and over-the-counter, predisposes both to a change in the epidemiologic patterns and the possible development of secondary resistance among previously susceptible yeast. This study was conducted to evaluate the aetiologic agents associated with mycotic vulvovaginitis and to review the appropriateness of prescribed antifungal therapy. Of 134 positive isolates, the most frequent yeast isolate was C. albicans accounting for 78%, C. tropicalis 10%, Prototheca wickerhamii (P. wickerhamii) 5%, C. glabrata 4%, Cryptococcus albidus (C. albidus) 2% and C. lusitaniae (1%) were also isolated. Of the positive cases, 75% were treated with antifungals, 17% with antibiotics and 8% were not treated. The azole group was the most frequently prescribed antifungal (71%). Of cases with negative yeast cultures, 83% were treated with antifungals. The presence of non-albicans Candida species and other opportunistic fungi is an important finding and combined with the pattern of therapy, represents a major challenge for future empirical therapeutic and prophylactic strategies in the treatment of mycotic vulvovaginitis.
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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
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Alvarez, Eduardo; Sanhueza, Camila
Scedosporium species are considered emerging agents causing illness in immunocompromised patients. In Chile, only Scedosporium apiospermum, Scedosporium boydii and Lomentospora prolificans haven been reported previously. The study aimed to characterize genetically Scedosporium dehoogii strains from Chilean soil samples, and assessed the antifungal susceptibility profile to classic and novel putative antifungal molecules. In 2014, several samples were obtained during a survey of soil fungi in urban areas from Chile. Morphological and phylogenetic analyses of the internal transcribed spacer region (ITS), tubulin (TUB), and calmodulin (CAL) sequences were performed. In addition, the susceptibility profiles to classic antifungal and new putative antifungal molecules were determined. Four strains of Scedosporium dehoogii were isolated from soil samples. The methodology confirmed the species (reported here as a new record for Chile). Antifungal susceptibility testing demonstrates the low activity of terpenes (α-pinene and geraniol) against this species. Voriconazole (VRC), posaconazole (PSC), and the hydroxyquinolines (clioquinol, and 5,7-dibromo-8-hydroxyquinoline) showed the best antifungal activity. Our results demonstrate that Scedosporium dehoogii is present in soil samples from Chile. This study shows also that hydroxyquinolines have potential as putative antifungal molecules. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.
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[Invasive fungal disease due to Scedosporium, Fusarium and mucorales].
Pemán, Javier; Salavert, Miguel
2014-01-01
The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. Copyright © 2014. Published by Elsevier Espana.
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Improved efficacy in onychomycosis therapy.
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.
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Bruni, Natascia; Capucchio, Maria Teresa; Biasibetti, Elena; Pessione, Enrica; Cirrincione, Simona; Giraudo, Leonardo; Corona, Antonio; Dosio, Franco
2016-06-11
Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).
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A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin
Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan
2014-01-01
Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064
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USDA-ARS?s Scientific Manuscript database
Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...
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Candida Species Biofilms’ Antifungal Resistance
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
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Posaconazole: an extended-spectrum triazole antifungal agent.
Schiller, Daryl S; Fung, Horatio B
2007-09-01
The incidence of invasive fungal infections (IFIs) caused by opportunistic filamentous molds is increasing, along with emerging fungal resistance. Posaconazole, a structural analogue of itraconazole that was approved for marketing in the United States in 2006, appears to be a promising antifungal agent. This article provides an overview of the pharmacology, efficacy, and tolerability of posaconazole when used for the prophylaxis and treatment of various common and rare fungal infections. Relevant information was identified through a search of MEDLINE (1966-April 2007), International Pharmaceutical Abstracts (1970-April 2007), and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy using the terms posaconazole and SCH 56592. Additional resources were found by searching the reference lists of the identified articles and the US Food and Drug Administration Web site. Posaconazole is available as an oral suspension. It is highly distributed to various sites, including bone, the central nervous system, and eye tissue. Its Vd is 2447 L when administered in multiple daily doses (up to 800 mg/d) in the presence of a high-fat meal. Because it is excreted mostly as unchanged drug in the feces (77%), posaconazole can be administered to patients with poor renal function without any dose adjustment. Posaconazole has shown in vitro and in vivo activity against a wide variety of fungi, including those that are rare and relatively resistant. Two clinical trials have compared posaconazole with fluconazole or itraconazole for the prophylaxis of IFIs in immunocompromised patients. The first, a randomized, double-blind trial in 600 recipients of hematopoietic stem cell transplants, found that overall rates of IFI did not differ significantly between posaconazole and fluconazole (5% vs 9%, respectively). The other, a randomized, open-label trial in 602 neutropenic patients, reported significantly fewer IFIs in patients receiving posaconazole compared with those receiving fluconazole or itraconazole (>2% vs >8%, respectively; P = 0.001). An additional 2 trials have investigated posaconazole for the treatment of oropharyngeal candidiasis (OPC) in patients with HIV infection. A randomized, controlled, evaluator-blinded study in 350 HIV-infected patients with OPC found similar 14-day clinical success rates with posaconazole and fluconazole (91.7% and 92.5%, respectively; 95% CI, -6.6l to 5.04), whereas an open-label study in 176 HIV-infected patients with a history of refractory OPC reported a 28-day clinical success rate of 75%. Numerous small studies and case reports have described successful posaconazole treatment of zygomycosis, aspergillosis, fusariosis, endemic dimorphic fungal infection, and superficial and subcutaneous fungal infections that were refractory to conventional antifungal agents or in patients who were unable to tolerate these agents. Posaconazole has been well tolerated. The most common complaints have been gastrointestinal in nature, including nausea (7%-8%) and diarrhea (3%-11%), although these have rarely led to permanent discontinuation of therapy. Other common adverse effects have included vomiting (4%-7%), headache (2%-8%), and liver enzyme elevations (2%-3%). Posaconazole suspension administered at up to 800 mg/d is a reasonable alternative to conventional antifungal agents for the prevention and treatment of IFIs in high-risk populations. It may also be suitable in patients with infections caused by rare or relatively resistant fungi, and those who are unable to tolerate long-term therapy with other antifungal agents.
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Enhancement of a Novel Isolate of Serratia plymuthica as Potential Candidate for an Antianthracnose.
Aisyah, Siti Nur; Harnas, Hafid; Sulastri, Sulastri; Retmi, Retmi; Fuaddi, Helmi; Fatchiyah, Fatchiyah; Bakhtiar, Amri; Jamsari, Jamsari
A new rhizobacteria isolate of Serratia plymuthica (strain UBCR_12) exhibited a promising potential as a biocontrol agent for anthracnose causing agent Colletotrichum gloeosporioides. The aim of this study was to characterize its antagonistic activity and explore the factors contributing to a higher inhibition activity. The antifungal effect of UBCR_12 against C. gloeosporioides was assayed under various pH values and nutritional sources. Culture supernatant obtained from UBCR_12 and C. gloeosporioides co-culture was also tested for its inhibitory activity. In addition, the antagonistic range of this isolate was examined against Sclerotium rolfsii and Fusarium oxysporum. Statistical analysis was done using one way analysis of variance and further processed using Fisher's Least Significant Difference (LSD) test with a p<0.05. The UBCR_12 induced inhibition was shown to be stable over time at pH 7, while peptone addition led to a faster induction (2 days after treatment) and glucose treatment to a higher activity. Of all these modifications, preliminary co-culture experiments with fungal cells resulted in the best antagonistic activity of UBCR_12 culture supernatant of about 30.66%. This isolate also showed a wide range of antagonistic activity due to its high suppression against S. rolfsii and F. oxysporum from soybean. Both environmental and biotic manipulations contributed an elevated inhibition rate of UBCR_12 against C. gloeosporioides. A proportional combination of the factors stimulating antagonistic activity of this strain is recommended to be utilized for the development of this strain as an antianthracnose. The enhanced antifungal effects of UBCR_12 resulted under each type of modification were varied indicating the difference of cell responses. It suggests that certain antifungal mechanism could be generated by modifying the environmental factor required for its induction. In addition, the application of cell-free culture supernatant provides an alternative solution in the utilization of biocontrol agents. For large scale application, it could minimize the risk of population outbreaks and harmful effects due to the living cells application.
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Troskie, Anscha Mari; Rautenbach, Marina; Delattin, Nicolas; Vosloo, Johan Arnold; Dathe, Margitta; Cammue, Bruno P A; Thevissen, Karin
2014-07-01
Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low-micromolar range. These tyrocidines also prevented C. albicans biofilm formation in vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Antifungal activity of β-carbolines on Penicillium digitatum and Botrytis cinerea.
Olmedo, Gabriela M; Cerioni, Luciana; González, M Micaela; Cabrerizo, Franco M; Rapisarda, Viviana A; Volentini, Sabrina I
2017-04-01
β-carbolines (βCs) are alkaloids widely distributed in nature that have demonstrated antimicrobial properties. Here, we tested in vitro six βCs against Penicillium digitatum and Botrytis cinerea, causal agents of postharvest diseases on fruit and vegetables. Full aromatic βCs (harmine, harmol, norharmane and harmane) exhibited a marked inhibitory effect on conidia germination at concentrations between 0.5 and 1 mM, while dihydro-βCs (harmalina and harmalol) only caused germination delay. Harmol showed the highest inhibitory effect on both fungal pathogens. After 24 h of exposure to 1 mM harmol, conidia revealed a severe cellular damage, exhibiting disorganized cytoplasm and thickened cell wall. Harmol antimicrobial effect was fungicidal on B. cinerea, while it was fungistatic on P. digitatum. Conidia membrane permeabilization was detected in treatments with harmol at sub-inhibitory and inhibitory concentrations, for both pathogens. In addition, residual infectivity of P. digitatum on lemons and B. cinerea on blueberries was significantly reduced after exposure to this alkaloid. It also inhibited mycelial growth, preventing sporulation at the highest concentration tested. These results indicate that harmol might be a promising candidate as a new antifungal molecule to control causal agents of fruit diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Ahmad, Aijaz; Khan, Amber; Manzoor, Nikhat
2013-01-23
Thymol (THY) and carvacrol (CARV), the principal chemical components of thyme oil have long been known for their wide use in medicine due to antimicrobial and disinfectant properties. This study, however, draws attention to a possible synergistic antifungal effect of these monoterpenes with azole antimycotic-fluconazole. Resistance to azoles in Candida albicans involves over-expression of efflux-pump genes MDR1, CDR1, CDR2 or mutations and over-expression of target gene ERG11. The inhibition of drug efflux pumps is considered a feasible strategy to overcome clinical antifungal resistance. To put forward this approach, we investigated the combination effects of these monoterpenes and FLC against 38 clinically obtained FLC-sensitive, and eleven FLC-resistant Candida isolates. Synergism was observed with combinations of THY-FLC and CARV-FLC evaluated by checkerboard microdilution method and nature of the interactions was calculated by FICI. In addition, antifungal activity was assessed using agar-diffusion and time-kill curves. The drug efflux activity was determined using two dyes, Rhodamine6G (R6G) and fluorescent Hoechst 33342. No significant differences were observed in dye uptakes between FLC-susceptible and resistant isolates, incubated in glucose free buffer. However, a significantly higher efflux was recorded in FLC-resistant isolates when glucose was added. Both monoterpenes inhibited efflux by 70-90%, showing their high potency to block drug transporter pumps. Significant differences, in the expression levels of CDR1 and MDR1, induced by monoterpenes revealed reversal of FLC-resistance. The selectively fungicidal characteristics and ability to restore FLC susceptibility in resistant isolates signify a promising candidature of THY and CARV as antifungal agents in combinational treatments for candidiasis. Copyright © 2012 Elsevier B.V. All rights reserved.
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de Morais, C B; Scopel, M; Pedrazza, G P R; da Silva, F K; Dalla Lana, D F; Tonello, M L; Miotto, S T S; Machado, M M; De Oliveira, L F S; Fuentefria, A M; Zuanazzi, J A S
2017-12-01
Intensive prophylactic use of antifungals leads to the increase of drug resistance and the need for new and more effective treatments are real. Plants from Leguminosae family are rich in flavonoids, for which numerous biological activities have been described, including antifungal effects. To screen methanolic extracts from Leguminosae species looking for alternative sources for antifungal agents (anti-dermatophyte and anti-Candida) and their innocuity. Antifungal activity was evaluated using the strains Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis, Epidermophyton floccosum, Trichophyton mentagrophytes, T. rubrum and, Microsporum gypseum in the broth microdilution method. Later, the minimum inhibitory concentration (MIC) for Mimosa pigra, Eriosema heterophyllum, and Chamaecrista nictitans was determined. The most promising extract was fractionated and cytotoxicity and genotoxicity of the most active fraction were also assayed. Fungicide and/or fungistatic activity against dermatophyte strains were presented by 60% of the methanolic extracts assayed. M. pigra, E. heterophyllum, and C. nictitans methanolic extracts could inhibit dermatophyte strains at concentrations ranging from 1.9 to 1000μg/mL. M. pigra showed the lowest MIC values for a dichloromethane fraction (1.9μg/mL) without DNA damage at 10 and 50μg/mL and 100% of cell viability of human leukocytes. Our results indicate that methanolic extracts from Leguminosae plants are potential sources of antifungal compounds, mainly the extract and fractions from M. pigra. The dichloromethane fraction from M. pigra did not showed in vitro toxicity according to the applied assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.
Roberts, Stephen K; McAinsh, Martin; Cantopher, Hanna; Sandison, Sean
2014-01-01
Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA) revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.
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Elaboration of antibiofilm surfaces functionalized with antifungal-cyclodextrin inclusion complexes.
Gharbi, Aïcha; Humblot, Vincent; Turpin, Frédéric; Pradier, Claire-Marie; Imbert, Christine; Berjeaud, Jean-Marc
2012-07-01
To tackle the loss of activity of surfaces functionalized by coating and covalently bound molecules to materials, an intermediate system implying the noncovalent immobilization of active molecules in the inner cavity of grafted cyclodextrins (CDs) was investigated. The antifungal and antibiofilm activities of the most stable complexes of Anidulafungin (ANF; echinocandin) and thymol (THY; terpen) in various CDs were demonstrated to be almost the same as the free molecules. The selected CD was covalently bond to self-assembled monolayers on gold surfaces. The immobilized antifungal agents reduced the number of culturable Candida albicans ATCC 3153 attached to the surface by 64 ± 8% for ANF and 75 ± 15% for THY. The inhibitory activity was persistent for THY-loaded samples, whereas it was completely lost for ANF-loaded surfaces after one use. However, reloading of the echinocandin restored the activity. Using fluorescent dying and confocal microscopy, it was proposed that the ANF-loaded surfaces inhibited the adherence of the yeasts, whereas the activity of immobilized THY was found fungicidal. This kind of tailored approach for functionalizing surfaces that could allow a progressive release of ANF or THY gave promising results but still needs to be improved to display a full activity. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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Koselny, Kristy; Green, Julianne; DiDone, Louis; Halterman, Justin P.; Fothergill, Annette W.; Wiederhold, Nathan P.; Patterson, Thomas F.; Cushion, Melanie T.; Rappelye, Chad; Wellington, Melanie
2016-01-01
Only one new class of antifungal drugs has been introduced into clinical practice in the last 30 years, and thus the identification of small molecules with novel mechanisms of action is an important goal of current anti-infective research. Here, we describe the characterization of the spectrum of in vitro activity and in vivo activity of AR-12, a celecoxib derivative which has been tested in a phase I clinical trial as an anticancer agent. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity, including activity against yeasts (e.g., Candida albicans, non-albicans Candida spp., Cryptococcus neoformans), molds (e.g., Fusarium, Mucor), and dimorphic fungi (Blastomyces, Histoplasma, and Coccidioides) with MICs of 2 to 4 μg/ml. AR-12 is also active against azole- and echinocandin-resistant Candida isolates, and subinhibitory AR-12 concentrations increase the susceptibility of fluconazole- and echinocandin-resistant Candida isolates. Finally, AR-12 also increases the activity of fluconazole in a murine model of cryptococcosis. Taken together, these data indicate that AR-12 represents a promising class of small molecules with broad-spectrum antifungal activity. PMID:27645246
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Aspergillus fumigatus-Related Species in Clinical Practice
Lamoth, Frédéric
2016-01-01
Aspergillus fumigatus is the main etiologic agent of invasive aspergillosis (IA). Other Aspergillus species belonging to the section Fumigati (A. fumigatus complex) may occasionally be the cause of IA. These strains are often misidentified, as they cannot be distinguished from A. fumigatus by conventional morphological analysis and sequencing methods. This lack of recognition may have important consequences as these A. fumigatus-related species often display some level of intrinsic resistance to azoles and other antifungal drugs. A. lentulus, A. udagawae, A. viridinutans, and A. thermomutatus (Neosartorya pseudofischeri) have been associated with refractory cases of IA. Microbiologists should be able to suspect the presence of these cryptic species behind a putative A. fumigatus isolate on the basis of some simple characteristics, such as defect in sporulation and/or unusual antifungal susceptibility profile. However, definitive species identification requires specific sequencing analyses of the beta-tubulin or calmodulin genes, which are not available in most laboratories. Multiplex PCR assays or matrix-assisted laser desorption ionization – time-of-flight mass spectrometry (MALDI-TOF MS) gave promising results for rapid and accurate distinction between A. fumigatus and other Aspergillus spp. of the section Fumigati in clinical practice. Improved diagnostic procedures and antifungal susceptibility testing may be helpful for the early detection and management of these particular IA cases. PMID:27242710
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Aspergillus fumigatus-Related Species in Clinical Practice.
Lamoth, Frédéric
2016-01-01
Aspergillus fumigatus is the main etiologic agent of invasive aspergillosis (IA). Other Aspergillus species belonging to the section Fumigati (A. fumigatus complex) may occasionally be the cause of IA. These strains are often misidentified, as they cannot be distinguished from A. fumigatus by conventional morphological analysis and sequencing methods. This lack of recognition may have important consequences as these A. fumigatus-related species often display some level of intrinsic resistance to azoles and other antifungal drugs. A. lentulus, A. udagawae, A. viridinutans, and A. thermomutatus (Neosartorya pseudofischeri) have been associated with refractory cases of IA. Microbiologists should be able to suspect the presence of these cryptic species behind a putative A. fumigatus isolate on the basis of some simple characteristics, such as defect in sporulation and/or unusual antifungal susceptibility profile. However, definitive species identification requires specific sequencing analyses of the beta-tubulin or calmodulin genes, which are not available in most laboratories. Multiplex PCR assays or matrix-assisted laser desorption ionization - time-of-flight mass spectrometry (MALDI-TOF MS) gave promising results for rapid and accurate distinction between A. fumigatus and other Aspergillus spp. of the section Fumigati in clinical practice. Improved diagnostic procedures and antifungal susceptibility testing may be helpful for the early detection and management of these particular IA cases.
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Optimization of chlorphenesin emulgel formulation.
Mohamed, Magdy I
2004-10-11
This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.
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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.
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Antifungal resistance: current trends and future strategies to combat
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
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Biofilm-forming capacity of blood-borne Candida albicans strains and effects of antifungal agents.
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.
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Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A.; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo
2017-01-01
Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans. PMID:28493889
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Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo
2017-01-01
Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20-30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.
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Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis
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
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Rogawansamy, Senthaamarai; Gaskin, Sharyn; Taylor, Michael; Pisaniello, Dino
2015-01-01
Fungal contamination in indoor environments has been associated with adverse health effects for the inhabitants. Remediation of fungal contamination requires removal of the fungi present and modifying the indoor environment to become less favourable to growth. This may include treatment of indoor environments with an antifungal agent to prevent future growth. However there are limited published data or advice on chemical agents suitable for indoor fungal remediation. The aim of this study was to assess the relative efficacies of five commercially available cleaning agents with published or anecdotal use for indoor fungal remediation. The five agents included two common multi-purpose industrial disinfectants (Cavicide® and Virkon®), 70% ethanol, vinegar (4.0%−4.2% acetic acid), and a plant-derived compound (tea tree (Melaleuca alternifolia) oil) tested in both a liquid and vapour form. Tea tree oil has recently generated interest for its antimicrobial efficacy in clinical settings, but has not been widely employed for fungal remediation. Each antifungal agent was assessed for fungal growth inhibition using a disc diffusion method against a representative species from two common fungal genera, (Aspergillus fumigatus and Penicillium chrysogenum), which were isolated from air samples and are commonly found in indoor air. Tea tree oil demonstrated the greatest inhibitory effect on the growth of both fungi, applied in either a liquid or vapour form. Cavicide® and Virkon® demonstrated similar, although less, growth inhibition of both genera. Vinegar (4.0%–4.2% acetic acid) was found to only inhibit the growth of P. chrysogenum, while 70% ethanol was found to have no inhibitory effect on the growth of either fungi. There was a notable inhibition in sporulation, distinct from growth inhibition after exposure to tea tree oil, Virkon®, Cavicide® and vinegar. Results demonstrate that common cleaning and antifungal agents differ in their capacity to inhibit the growth of fungal genera found in the indoor air environment. The results indicate that tea tree oil was the most effective antifungal agent tested, and may have industrial application for the remediation of fungal contamination in residential and occupational buildings. PMID:26042369
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Rogawansamy, Senthaamarai; Gaskin, Sharyn; Taylor, Michael; Pisaniello, Dino
2015-06-02
Fungal contamination in indoor environments has been associated with adverse health effects for the inhabitants. Remediation of fungal contamination requires removal of the fungi present and modifying the indoor environment to become less favourable to growth. This may include treatment of indoor environments with an antifungal agent to prevent future growth. However there are limited published data or advice on chemical agents suitable for indoor fungal remediation. The aim of this study was to assess the relative efficacies of five commercially available cleaning agents with published or anecdotal use for indoor fungal remediation. The five agents included two common multi-purpose industrial disinfectants (Cavicide® and Virkon®), 70% ethanol, vinegar (4.0%-4.2% acetic acid), and a plant-derived compound (tea tree (Melaleuca alternifolia) oil) tested in both a liquid and vapour form. Tea tree oil has recently generated interest for its antimicrobial efficacy in clinical settings, but has not been widely employed for fungal remediation. Each antifungal agent was assessed for fungal growth inhibition using a disc diffusion method against a representative species from two common fungal genera, (Aspergillus fumigatus and Penicillium chrysogenum), which were isolated from air samples and are commonly found in indoor air. Tea tree oil demonstrated the greatest inhibitory effect on the growth of both fungi, applied in either a liquid or vapour form. Cavicide® and Virkon® demonstrated similar, although less, growth inhibition of both genera. Vinegar (4.0%-4.2% acetic acid) was found to only inhibit the growth of P. chrysogenum, while 70% ethanol was found to have no inhibitory effect on the growth of either fungi. There was a notable inhibition in sporulation, distinct from growth inhibition after exposure to tea tree oil, Virkon®, Cavicide® and vinegar. Results demonstrate that common cleaning and antifungal agents differ in their capacity to inhibit the growth of fungal genera found in the indoor air environment. The results indicate that tea tree oil was the most effective antifungal agent tested, and may have industrial application for the remediation of fungal contamination in residential and occupational buildings.
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Advances in the treatment of invasive neonatal candidiasis
Botero-Calderon, Lorena; Benjamin, Daniel K.; Cohen-Wolkowiez, Michael
2015-01-01
Introduction Invasive candidiasis is responsible for approximately 10% of nosocomial sepsis in very-low-birth-weight (VLBW) infants and is associated with substantial morbidity and mortality. Over the last 2 decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking. Areas covered We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis. Expert opinion Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data collected thus far or data submitted to regulatory agencies for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates. PMID:25842986
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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.
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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.
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Graphene Oxide-Based Nanocomposites Decorated with Silver Nanoparticles as an Antibacterial Agent
NASA Astrophysics Data System (ADS)
Jaworski, Sławomir; Wierzbicki, Mateusz; Sawosz, Ewa; Jung, Anna; Gielerak, Grzegorz; Biernat, Joanna; Jaremek, Henryk; Łojkowski, Witold; Woźniak, Bartosz; Wojnarowicz, Jacek; Stobiński, Leszek; Małolepszy, Artur; Mazurkiewicz-Pawlicka, Marta; Łojkowski, Maciej; Kurantowicz, Natalia; Chwalibog, André
2018-04-01
One of the most promising methods against drug-resistant bacteria can be surface-modified materials with biocidal nanoparticles and nanocomposites. Herein, we present a nanocomposite with silver nanoparticles (Ag-NPs) on the surface of graphene oxide (GO) as a novel multifunctional antibacterial and antifungal material. Ultrasonic technologies have been used as an effective method of coating polyurethane foils. Toxicity on gram-negative bacteria ( Escherichia coli), gram-positive bacteria ( Staphylococcus aureus and Staphylococcus epidermidis), and pathogenic yeast ( Candida albicans) was evaluated by analysis of cell morphology, assessment of cell viability using the PrestoBlue assay, analysis of cell membrane integrity using the lactate dehydrogenase assay, and reactive oxygen species production. Compared to Ag-NPs and GO, which have been widely used as antibacterial agents, our nanocomposite shows much higher antimicrobial efficiency toward bacteria and yeast cells.
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Graphene Oxide-Based Nanocomposites Decorated with Silver Nanoparticles as an Antibacterial Agent.
Jaworski, Sławomir; Wierzbicki, Mateusz; Sawosz, Ewa; Jung, Anna; Gielerak, Grzegorz; Biernat, Joanna; Jaremek, Henryk; Łojkowski, Witold; Woźniak, Bartosz; Wojnarowicz, Jacek; Stobiński, Leszek; Małolepszy, Artur; Mazurkiewicz-Pawlicka, Marta; Łojkowski, Maciej; Kurantowicz, Natalia; Chwalibog, André
2018-04-23
One of the most promising methods against drug-resistant bacteria can be surface-modified materials with biocidal nanoparticles and nanocomposites. Herein, we present a nanocomposite with silver nanoparticles (Ag-NPs) on the surface of graphene oxide (GO) as a novel multifunctional antibacterial and antifungal material. Ultrasonic technologies have been used as an effective method of coating polyurethane foils. Toxicity on gram-negative bacteria (Escherichia coli), gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), and pathogenic yeast (Candida albicans) was evaluated by analysis of cell morphology, assessment of cell viability using the PrestoBlue assay, analysis of cell membrane integrity using the lactate dehydrogenase assay, and reactive oxygen species production. Compared to Ag-NPs and GO, which have been widely used as antibacterial agents, our nanocomposite shows much higher antimicrobial efficiency toward bacteria and yeast cells.
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Antifungal Therapy in Birds: Old Drugs in a New Jacket.
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.
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Antibacterial and Antifungal Activities of Spices
Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin
2017-01-01
Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices—such as clove, oregano, thyme, cinnamon, and cumin—possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives. PMID:28621716
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Antibacterial and Antifungal Activities of Spices.
Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin
2017-06-16
Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices-such as clove, oregano, thyme, cinnamon, and cumin-possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens , pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.
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Savi, Geovana D; Cardoso, William A; Furtado, Bianca G; Bortolotto, Tiago; Zanoni, Elton T; Scussel, Rahisa; Rezende, Lucas F; Machado-de-Ávila, Ricardo A; Montedo, Oscar R K; Angioletto, Elidio
2018-03-04
Zeolites are often used as adsorbents materials and their loaded cations can be exchanged with metal ions in order to add antimicrobial properties. The aim of this study was to use the 4A zeolite and its derived ion-exchanged forms with Zn 2+ , Li + , Cu 2+ and Co 2+ in order to evaluate their antifungal properties against Fusarium graminearum, including their capacity in terms of metal ions release, conidia germination and the deoxynivalenol (DON) adsorption. The zeolites ion-exchanged with Li + , Cu 2+ , and Co 2+ showed an excellent antifungal activity against F. graminearum, using an agar diffusion method, with a zone of inhibition observed around the samples of 45.3 ± 0.6 mm, 25.7 ± 1.5 mm, and 24.7 ± 0.6 mm, respectively. Similar results using agar dilution method were found showing significant growth inhibition of F. graminearum for ion-exchanged zeolites with Zn 2+ , Li + , Cu 2+ , and Co 2+ . The fungi growth inhibition decreased as zeolite-Cu 2+ >zeolite-Li + >zeolite-Co 2+ >zeolite-Zn 2+ . In addition, the conidia germination was strongly affected by ion-exchanged zeolites. With regard to adsorption capacity, results indicate that only zeolite-Li + were capable of DON adsorption significantly (P < 0.001) with 37% at 2 mg mL -1 concentration. The antifungal effects of the ion-exchanged zeolites can be ascribed to the interactions of the metal ions released from the zeolite structure, especially for zeolite-Li + , which showed to be a promising agent against F. graminearum and its toxin.
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Kumar, C Ganesh; Poornachandra, Y
2015-01-01
The recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. Considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of Delftia sp. strain KCM-006 and their application as antifungal agents and as a drug carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical and monodispersed silver nanoparticles with an average size of 9.8 nm. The synthesized nanoparticles were found to be photoluminescent, highly stable and crystalline in nature having a zeta potential of -31 mV. The silver nanoparticles exhibited very good antifungal activity against various pathogenic Candida strains. Furthermore, the efficacy of nanoparticles was increased by conjugating the antifungal drug Miconazole to silver nanoparticles which exhibited significant fungicidal activity, inhibition of ergosterol biosynthesis and biofilm inhibition by increasing ROS levels. In addition, the cell viability and immunocytochemistry analysis against different normal cell lines including Chinese hamster ovary cells (CHO), human lung cell line (MRC5) and human vascular endothelial cells (HUVEC) demonstrated that these nanoparticles were non-toxic up to a concentration of 20 μM. In conclusion, these results suggest that the synthesized nanoparticles find application as both antifungal agents and drug delivery vehicles. This is a first report on the preparation of silver nanoparticles using culture supernatant from Delftia sp. and also on the conjugation of Miconazole, an antifungal drug, to the bacterial silver nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.
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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
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Antifungal potential of marine natural products.
El-Hossary, Ebaa M; Cheng, Cheng; Hamed, Mostafa M; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan
2017-01-27
Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Antimicrobial Susceptibility of Tinea Capitis in Children from Egypt.
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.
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Boron chemicals in diagnosis and therapeutics
Das, Bhaskar C; Thapa, Pritam; Karki, Radha; Schinke, Caroline; Das, Sasmita; Kambhampati, Suman; Banerjee, Sushanta K; Van Veldhuizen, Peter; Verma, Amit; Weiss, Louis M; Evans, Todd
2013-01-01
Advances in the field of boron chemistry have expanded the application of boron from material use to medicine. Boron-based drugs represent a new class of molecules that possess several biomedical applications including use as imaging agents for both optical and nuclear imaging as well as therapeutic agents with anticancer, antiviral, antibacterial, antifungal and other disease-specific activities. For example, bortezomib (Velcade®), the only drug in clinical use with boron as an active element, was approved in 2003 as a proteasome inhibitor for the treatment of multiple myeloma and non-Hodgkin’s lymphoma. Several other boron-based compounds are in various phases of clinical trials, which illustrates the promise of this approach for medicinal chemists working in the area of boron chemistry. It is expected that in the near future, several boron-containing drugs should become available in the market with better efficacy and potency than existing drugs. This article discusses the current status of the development of boron-based compounds as diagnostic and therapeutic agents in humans. PMID:23617429
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Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko
2017-01-01
Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.
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Yasmin, Nusrat; Saleem, Mahjabeen; Naz, Mamoona; Gul, Roquyya; Rehman, Hafiz Muzzammel
2017-01-01
A thaumatin-like protein gene from Basrai banana was cloned and expressed in Escherichia coli . Amplified gene product was cloned into pTZ57R/T vector and subcloned into expression vector pET22b(+) and resulting pET22b-basrai TLP construct was introduced into E. coli BL21. Maximum protein expression was obtained at 0.7 mM IPTG concentration after 6 hours at 37°C. Western blot analysis showed the presence of approximately 20 kDa protein in induced cells. Basrai antifungal TLP was tried as pharmacological agent against fungal disease. Independently Basrai antifungal protein and amphotericin B exhibited their antifungal activity against A. fumigatus ; however combined effect of both agents maximized activity against the pathogen. Docking studies were performed to evaluate the antimicrobial potential of TLP against A. fumigatus by probing binding pattern of antifungal protein with plasma membrane ergosterol of targeted fungal strain. Ice crystallization primarily damages frozen food items; however addition of antifreeze proteins limits the growth of ice crystal in frozen foods. The potential of Basrai TLP protein, as an antifreezing agent, in controlling the ice crystal formation in frozen yogurt was also studied. The scope of this study ranges from cost effective production of pharmaceutics to antifreezing and food preserving agent as well as other real life applications.
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Yasmin, Nusrat; Naz, Mamoona; Gul, Roquyya; Rehman, Hafiz Muzzammel
2017-01-01
A thaumatin-like protein gene from Basrai banana was cloned and expressed in Escherichia coli. Amplified gene product was cloned into pTZ57R/T vector and subcloned into expression vector pET22b(+) and resulting pET22b-basrai TLP construct was introduced into E. coli BL21. Maximum protein expression was obtained at 0.7 mM IPTG concentration after 6 hours at 37°C. Western blot analysis showed the presence of approximately 20 kDa protein in induced cells. Basrai antifungal TLP was tried as pharmacological agent against fungal disease. Independently Basrai antifungal protein and amphotericin B exhibited their antifungal activity against A. fumigatus; however combined effect of both agents maximized activity against the pathogen. Docking studies were performed to evaluate the antimicrobial potential of TLP against A. fumigatus by probing binding pattern of antifungal protein with plasma membrane ergosterol of targeted fungal strain. Ice crystallization primarily damages frozen food items; however addition of antifreeze proteins limits the growth of ice crystal in frozen foods. The potential of Basrai TLP protein, as an antifreezing agent, in controlling the ice crystal formation in frozen yogurt was also studied. The scope of this study ranges from cost effective production of pharmaceutics to antifreezing and food preserving agent as well as other real life applications. PMID:28875151
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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.
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Synthesis and evaluation of α-Ag2WO4 as novel antifungal agent
NASA Astrophysics Data System (ADS)
Foggi, Camila C.; Fabbro, Maria T.; Santos, Luís P. S.; de Santana, Yuri V. B.; Vergani, Carlos E.; Machado, Ana L.; Cordoncillo, Eloisa; Andrés, Juan; Longo, Elson
2017-04-01
Because of the need for new antifungal materials with greater potency, microcrystals of α-Ag2WO4, a complex metal oxide, have been synthetized by a simple co-precipitation method, and their antifungal activity against Candida albicans has been investigated. A theoretical model based on clusters that are building blocks of α-Ag2WO4 has been proposed to explain the experimental results.
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Risk of Fungemia Due to Rhodotorula and Antifungal Susceptibility Testing of Rhodotorula Isolates
Zaas, Aimee K.; Boyce, Molly; Schell, Wiley; Lodge, Barbara Alexander; Miller, Jackie L.; Perfect, John R.
2003-01-01
Rhodotorula infections occur among patients with immunosuppression and/or central venous catheters. Using standardized methods (NCCLS M27-A), we determined the antifungal susceptibilities of 10 Rhodotorula bloodstream infection isolates. Patient information was collected for clinical correlation. The MICs of amphotericin B and posaconazole were the lowest, and the MICs of triazoles and echinocandins were higher than those of other antifungal agents. PMID:14605170
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Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives.
Petrova, Krasimira T; Potewar, Taterao M; Correia-da-Silva, Paula; Barros, M Teresa; Calhelha, Ricardo C; Ćiric, Ana; Soković, Marina; Ferreira, Isabel C F R
2015-11-19
A library of 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-1,2,3-triazoles have been investigated for their antibacterial, antifungal and cytotoxic activities. Most of the target compounds showed good inhibitory activity against a variety of clinically and food contaminant important microbial pathogens. In particular, 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-pentylphenyl)-1,2,3-triazole (5) was highly active against all the tested bacteria with minimal inhibitory concentrations (MICs) ranging between 1.1 and 4.4 µM and bactericidal concentrations (MBCs) from 2.2 and 8.4 µM. The compound 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-bromophenyl)-1,2,3-triazole (3) showed antifungal activity with MICs from 0.6 to 4.8 µM and minimal fungicidal concentrations (MFCs) ranging between 1.2 and 8.9 µM. Furthermore, some of the compounds possessed moderate cytotoxicity against human breast, lung, cervical and hepatocellular carcinoma cell lines, without showing toxicity for non-tumor liver cells. The above mentioned derivatives represent promising leads for the development of new generation of sugar-triazole antifungal agents. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Antimicrobial Octapeptin C4 Analogues Active against Cryptococcus Species.
Chitty, Jessica L; Butler, Mark S; Suboh, Azzah; Edwards, David J; Cooper, Matthew A; Fraser, James A; Robertson, Avril A B
2018-02-01
Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogen Cryptococcus neoformans is a significant contributor to mortality, and its growing resistance to current antifungals is an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal. Octapeptin C4 was a potent, selective inhibitor of this fungal pathogen with an MIC of 1.56 μg/ml. Further testing of octapeptin C4 against 40 clinical isolates of C. neoformans var. grubii or neoformans showed an MIC of 1.56 to 3.13 μg/ml, while 20 clinical isolates of C. neoformans var. gattii had an MIC of 0.78 to 12.5 μg/ml. In each case, the MIC values for octapeptin C4 were equivalent to, or better than, current antifungal drugs fluconazole and amphotericin B. The negatively charged polysaccharide capsule of C. neoformans influences the pathogen's sensitivity to octapeptin C4, whereas the degree of melanization had little effect. Testing synthetic octapeptin C4 derivatives provided insight into the structure activity relationships, revealing that the lipophilic amino acid moieties are more important to the activity than the cationic diaminobutyric acid groups. Octapeptins have promising potential for development as anticryptococcal therapeutic agents. Copyright © 2018 Chitty et al.
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Antimicrobial Octapeptin C4 Analogues Active against Cryptococcus Species
Chitty, Jessica L.; Butler, Mark S.; Suboh, Azzah; Edwards, David J.; Cooper, Matthew A.; Fraser, James A.
2017-01-01
ABSTRACT Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogen Cryptococcus neoformans is a significant contributor to mortality, and its growing resistance to current antifungals is an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal. Octapeptin C4 was a potent, selective inhibitor of this fungal pathogen with an MIC of 1.56 μg/ml. Further testing of octapeptin C4 against 40 clinical isolates of C. neoformans var. grubii or neoformans showed an MIC of 1.56 to 3.13 μg/ml, while 20 clinical isolates of C. neoformans var. gattii had an MIC of 0.78 to 12.5 μg/ml. In each case, the MIC values for octapeptin C4 were equivalent to, or better than, current antifungal drugs fluconazole and amphotericin B. The negatively charged polysaccharide capsule of C. neoformans influences the pathogen's sensitivity to octapeptin C4, whereas the degree of melanization had little effect. Testing synthetic octapeptin C4 derivatives provided insight into the structure activity relationships, revealing that the lipophilic amino acid moieties are more important to the activity than the cationic diaminobutyric acid groups. Octapeptins have promising potential for development as anticryptococcal therapeutic agents. PMID:29158283
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NASA Astrophysics Data System (ADS)
Shin, Joongmin; Liu, Xiaojing; Chikthimmah, Naveen; Lee, Youn Suk
2016-11-01
The purpose of this study was to develop an active non-migratory antifungal Low Density Polyethylene (LDPE) polymer for use in food packaged applications. The functional acrylic acid monomer was grafted on the LDPE film surface by photo-initiated graft polymerization using Ultra Violet light irradiation (from 0 to 5 min). Natamycin, an antifungal agent, was applied to the treated film to bind with the pendent functional groups and were evaluated its performance against mold and yeast. The grafted amounts were determined by gravimetric measurement and dye absorbance. Attenuated Total Reflectance/Fourier Transfer Infrared Spectroscopy, scanning electron microscopy, mechanical strength test was used to characterize film properties. The antifungal efficacy of the film was evaluated with Saccharomyces cerevisiae and Penicillium chrysogenum on growth media and fresh cut cantaloupe. The amounts of the grafted group were increased with the longer ultraviolet exposure time. The amount of the grafted natamycin on the treated film was up to 49.87 μg/cm2, and the film inhibited mycelium formation of P. chrysogenum spores by over 60%. Due to the thickness of the film (less than 12.25 μm), long time UV exposure decrease the film's mechanical strength. The application of such non-migratory active packaging film represents a promising approach to maintaining food quality with reduced additive.
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Alves, Izabel Almeida; Bandeira, Laíssa Arévalo; Mario, Débora Alves Nunes; Denardi, Laura Bedin; Neves, Louise Vignoles; Santurio, Janio Morais; Alves, Sydney Hartz
2012-09-01
The rise of Candida spp. resistant to classic triazole antifungal agents has led to a search for new therapeutic options. Here, we evaluated combinations of antifungals in a checkerboard assay against two groups of Candida glabrata strains: one containing fluconazole-susceptible clinical isolates (FS) and another containing fluconazole-resistant laboratory derivative (FR). The most synergistic combination observed was amphotericin B + flucytosine (synergistic for 61.77 % of FS strains and 76.47 % of FR strains). The most antagonistic combination observed was ketoconazole + flucytosine (FS 61.77 % and FR 55.88 %). Surprisingly, most combinations evidenced indifferent interactions, and the best synergism appeared when amphotericin B and flucytosine were combined against both groups of isolates.
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Stratov, I; Korman, T M; Johnson, P D R
2003-05-01
Presented here is a case of Aspergillus osteomyelitis in an immunocompetent patient that progressed despite surgery and prolonged treatment with liposomal amphotericin B; the report is followed by a review of the literature. The review of this case and 41 similar cases found an overall cure rate of 69%. The importance of surgery when amphotericin B is used as first-line therapy is indicated by a 14% cure rate when amphotericin B is used alone compared to 75% when combined with surgery. When therapy is failing or surgery is contraindicated, dose escalation using a lipid formulation was not effective. On review, the addition of another agent, in particular 5-fluorocytosine, appears to be more beneficial. The patient reported here responded rapidly to voriconazole, a promising new antifungal agent for Aspergillus infections.
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Bactericidal Activity of Usnic Acid-Loaded Electrospun Fibers.
Araújo, Evando S; Pereira, Eugênia C; da Costa, Mateus M; da Silva, Nicácio H; de Oliveira, Helinando P
2016-01-01
Usnic acid has been progressively reported in the literature as one of the most important lichen metabolites characterized by a rich diversity of applications such as antifungal, antimicrobial, antiprotozoal and antiviral agent. Particularly, antimicrobial activity of usnic acid can be improved by encapsulation of active molecules in enteric electrospun fibers, allowing the controlled release of active molecule at specific pH. Few relevant patents to the topic have been reviewed and cited. Bactericidal activity of usnic acid-loaded electrospun fibers of Eudragit L-100 and polyvinylpyrrolidone was examined against Staphylococcus aureus using inhibition hales methodology. The controlled release of active material at high pH is established after 10 minutes of interaction with media and results in reasonable activity against S. aureus, as detected by inhibition hales. The strong biological activity of usnic acid-loaded electrospun fibers provides a promising application for corresponding material as a bactericidal agent for wound healing treatment.
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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.
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Neosordarin and hydroxysordarin, two new antifungal agents from Sordaria araneosa.
Davoli, Paolo; Engel, Günther; Werle, Andreas; Sterner, Olov; Anke, Timm
2002-04-01
Two novel antifungal agents belonging to the sordarin family have been isolated from fermentations of Sordaria araneosa by bioassay-guided purification and their structures elucidated by NMR techniques. Neosordarin (1) is closely related to the recently discovered hypoxysordarin (2), with only small differences on the aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose moiety. Hydroxysordarin (3) closely resembles sordarin (4), the only slight difference being the replacement of sordarose with altrose as the sugar unit.
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Patel, Gopal A; Wiederkehr, Michael; Schwartz, Robert A
2009-09-01
Tinea cruris is an intensely pruritic fungal infection of the groin and adjacent skin. Also known as crotch rot and jock itch, it can be a troubling important entity that at times is a clinical, diagnostic, and therapeutic challenge. Predisposing factors include heat, humidity, and hyperhidrosis, common accompaniments of high school-aged athletes. Furthermore, obesity and diabetes mellitus, additional risk factors for tinea cruris, are reaching unprecedented levels in adolescents. Treatment options range from improving hygiene to topical antifungal agents and systemic antifungal agents, the latter with potentially dangerous side effects.
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Antifungal Activity of Propolis Against Yeasts Isolated From Blood Culture: In Vitro Evaluation.
Mutlu Sariguzel, Fatma; Berk, Elife; Koc, Ayes Nedret; Sav, Hafize; Demir, Gonca
2016-09-01
Due to the failure of available antifungal agents in the treatment of candidemia and the toxic activities of these drugs, a lot of researches are being conducted to develop new nontoxic and effective antifungal agents for optimal control of fungal pathogens. The aim of this study is to evaluate the in vitro antifungal activity of propolis against yeasts isolated from the blood cultures of intensive care unit patients. Seventy-six strains were included in this study. The in vitro antifungal activity of propolis, fluconazole (FLU), and itraconazole (ITR) was investigated by the microdilution broth methods (CLSI guidelines M27-A3 for yeast). The propolis sample was collected from Kayseri, Turkey. Of the 76 isolates, 33 were identified as Candida albicans while 37 were C. parapsilosis, three were C. tropicalis, and three were identified as C. glabrata. The geometric mean range for MIC (μg/ml) with regard to all isolates was 0.077 to 3 μg/ml for FLU and ITR, and 0.375 to 0.70 μg/ml for propolis. It was shown that propolis had significant antifungal activity against all Candida strains and the MIC range of propolis was determined as 0185 to 3 μg/ml. This study demonstrated that propolis had significant antifungal activity against yeasts isolated from blood culture compared with FLU and ITR. The propolis MIC in azole-resistant strains such as C. glabrata was found lower than the FLU MIC. © 2015 Wiley Periodicals, Inc.
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SUSCEPTIBILITY TEST FOR FUNGI: CLINICAL AND LABORATORIAL CORRELATIONS IN MEDICAL MYCOLOGY.
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.
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Enhancement of the antifungal activity of antimicrobial drugs by Eugenia uniflora L.
Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique Douglas Melo
2013-07-01
Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity.
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Deng, Shuwen; Ansari, Saham; Rafati, Haleh; Taghizadeh-Armaki, Mojtaba; Nasrollahi-Omran, Ayatollah; Tolooe, Ali; Zhan, Ping; Liao, Wanqing; van der Lee, Henrich A.; Verweij, Paul E.
2016-01-01
ABSTRACT Trichophyton schoenleinii is an anthropophilic dermatophyte mainly causing tinea favosa of the scalp in certain regions of the world, especially Africa and Asia. We investigated the in vitro susceptibilities of 55 T. schoenleinii isolates collected over the last 30 years from Iran, Turkey, and China to 12 antifungals using the CLSI broth microdilution method. Our results revealed that terbinafine and ketoconazole were the most potent antifungal agents among those tested, independently of the geographic regions where strains were isolated. PMID:27956429
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Deng, Shuwen; Ansari, Saham; Ilkit, Macit; Rafati, Haleh; Hedayati, Mohammad T; Taghizadeh-Armaki, Mojtaba; Nasrollahi-Omran, Ayatollah; Tolooe, Ali; Zhan, Ping; Liao, Wanqing; van der Lee, Henrich A; Verweij, Paul E; Seyedmousavi, Seyedmojtaba
2017-02-01
Trichophyton schoenleinii is an anthropophilic dermatophyte mainly causing tinea favosa of the scalp in certain regions of the world, especially Africa and Asia. We investigated the in vitro susceptibilities of 55 T. schoenleinii isolates collected over the last 30 years from Iran, Turkey, and China to 12 antifungals using the CLSI broth microdilution method. Our results revealed that terbinafine and ketoconazole were the most potent antifungal agents among those tested, independently of the geographic regions where strains were isolated. Copyright © 2017 American Society for Microbiology.
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Antimicrobial Susceptibility of Tinea Capitis in Children from Egypt
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
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Caneschi, César A.; Senra, Mônica P.; Carvalho, Gustavo S. G.; da Silva, Adilson D.
2017-01-01
Nitrogenated heterocyclic compounds are present in both natural and synthetic drugs, and hexahydropyrimidine derivatives may prove to be efficient in treating dermatomycosis causing fungi. This study evaluated the antifungal activity of four hexahydropyrimidine derivatives against the dermatomycosis causing fungi. These derivatives were synthesized, characterized, and assessed in terms of their activity against Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Fusarium oxysporum, and Epidermophyton floccosum between concentrations 7.8 and 1,000 μg mL−1. Scanning electron micrographs were assessed for the active derivatives and reference drugs, and these micrographs revealed that new agents cause morphological changes in fungi. The derivatives HHP1, HHP3, and HHP4 revealed poor activity against the four fungal strains (MICs range 500–1000 μg mL−1). Compound HHP3 was found to be the best potential antifungal agent among those tested and was the most effective among all the active derivatives that caused morphological changes in the susceptible strains. PMID:29226215
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Antifungal therapy for keratomycoses.
Ganegoda, Nihal; Rao, Srinivas K
2004-04-01
Keratomycoses have recently emerged as an important cause of ocular morbidity, especially in third-world countries. Available antifungal agents are limited in their efficacy, due to limited penetration into the cornea, the fungistatic nature and the development of drug resistance. Effective usage of the available drugs is hampered by the inefficiency of currently available antibiotic sensitivity tests for fungal organisms. There is also limited knowledge regarding the ideal combination(s) of antifungal agents, including issues of synergism and antagonism. Despite these problems, recent publications indicate encouraging outcomes in the treatment of a large series of fungal keratitis. Advances include better drug formulations, new agents and novel methods of drug delivery into the eye. As our ability to deal with advanced fungal keratitis remains limited, the importance of early diagnosis has been stressed and molecular biological techniques may play an important role in the future. This article summarises the important new advances in these areas in the past 2 years and provides guidelines for the management of these serious corneal infections.
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Antimicrobial Dendrimeric Peptides: Structure, Activity and New Therapeutic Applications
Scorciapino, Mariano A.; Serra, Ilaria; Manzo, Giorgia; Rinaldi, Andrea C.
2017-01-01
Microbial resistance to conventional antibiotics is one of the most outstanding medical and scientific challenges of our times. Despite the recognised need for new anti-infective agents, however, very few new drugs have been brought to the market and to the clinic in the last three decades. This review highlights the properties of a new class of antibiotics, namely dendrimeric peptides. These intriguing novel compounds, generally made of multiple peptidic sequences linked to an inner branched core, display an array of antibacterial, antiviral and antifungal activities, usually coupled to low haemolytic activity. In addition, several peptides synthesized in oligobranched form proved to be promising tools for the selective treatment of cancer cells. PMID:28273806
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Antimicrobial Dendrimeric Peptides: Structure, Activity and New Therapeutic Applications.
Scorciapino, Mariano A; Serra, Ilaria; Manzo, Giorgia; Rinaldi, Andrea C
2017-03-03
Microbial resistance to conventional antibiotics is one of the most outstanding medical and scientific challenges of our times. Despite the recognised need for new anti-infective agents, however, very few new drugs have been brought to the market and to the clinic in the last three decades. This review highlights the properties of a new class of antibiotics, namely dendrimeric peptides. These intriguing novel compounds, generally made of multiple peptidic sequences linked to an inner branched core, display an array of antibacterial, antiviral and antifungal activities, usually coupled to low haemolytic activity. In addition, several peptides synthesized in oligobranched form proved to be promising tools for the selective treatment of cancer cells.
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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.
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Wani, Mohmmad Younus; Ahmad, Aijaz; Kumar, Santosh; Sobral, Abilio J F N
2017-04-01
Invasive fungal infection is a problem that continues to challenge the healthcare sector. New antifungals and new therapeutic strategies are needed to address this challenge. We previously reported that the combination of a synthetic compound with a drug with known mechanism of action is a good strategy to treat aggressive and resistant fungi. Here we revisited our approach and synthesized structural analogues of flucytosine, which is a synthetic antifungal and is being studied for its use in combination therapy with other antifungal drugs. Pyrimidin-one and -thione (often known as DHPM's) as flucytosine analogues were obtained through a Biginelli reaction of corresponding aldehydes, ethylacetoacetate and urea/thiourea. Structure was confirmed by FTIR, 1 HNMR, 13 CNMR, COSY and MS (ESI + ) analysis. All the newly synthesized derivatives were evaluated for the antifungal activity alone and in combination of two most commonly used antifungal drugs, amphotericin B and fluconazole against different clinically isolated Candida albicans strains. Minimum inhibitory concentration results confirmed that BG4 possess high antifungal activity against all the tested strains (MIC = 1-32 μg/ml). For all the combinations with amphotericin B and fluconazole, 37% were synergistic followed by 30% additive and 24% indifferent interactions. Interestingly, 9% antagonistic interaction was observed when BG1 and BG3 were combined with fluconazole, however, no antagonistic interaction was observed with amphotericin B. In-depth studies of all the synergies were done by constructing isobolograms with nine different ratio combinations. These results warrant the use of DHPM derivatives as chemosensitising agents which could lower down the dosages of the antifungal drugs to treat invasive fungal diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.
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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.
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8-Amido-Bearing pseudomycin B (PSB) analogue: novel antifungal agents.
Zhang, Y Z; Sun, X; Zeckner, D J; Sachs, R K; Current, W L; Chen, S H
2001-01-22
During the course of a structure-activity relationship (SAR) study on novel depsinonapeptide pseudomycin B, we synthesized a total of 12 8-amidopseudomycin analogues via standard two-step sequence from either ZPSB 2 or AllocPSB 3. A number of these amides exhibited good in vitro antifungal activities.
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Cinnamic acid analogs as intervention catalysts for overcoming antifungal tolerance
USDA-ARS?s Scientific Manuscript database
Antifungal potency of thirty-three cinnamic acid derivatives was investigated. The efficacy of caspofungin (CAS) or octyl gallate (OG), the cell wall disrupting agents, was augmented by 4-chloro-a-methyl- or 4-methylcinnamic acid screened. Synergistic chemosensitization by 4-chloro-a-methyl- or 4-me...
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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.
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Antifungal activity of plant extracts against Aspergillus niger and Rhizopus stolonifer.
Surapuram, Venkatasaichaitanya; Setzer, William N; McFeeters, Robert L; McFeeters, Hana
2014-11-01
Despite recent advances in antifungal development, fungi remain a devastating threat to human health and compromise viability of the food supply. Plant based antimicrobials represent a vast untapped source with tremendous potential. Herein we present the antifungal properties of more than 50 plant extracts against two important human and agricultural pathogens, Aspergillus niger and Rhizopus stolonifer. Multiple extracts exhibit promising MIC values of less than 100 μg/mL and are reported for both fungal species.
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Romo, Jesus A.; Pierce, Christopher G.; Chaturvedi, Ashok K.; Lazzell, Anna L.; McHardy, Stanton F.
2017-01-01
ABSTRACT Candida albicans remains the main etiologic agent of candidiasis, the most common fungal infection and now the third most frequent infection in U.S. hospitals. The scarcity of antifungal agents and their limited efficacy contribute to the unacceptably high morbidity and mortality rates associated with these infections. The yeast-to-hypha transition represents the main virulence factor associated with the pathogenesis of C. albicans infections. In addition, filamentation is pivotal for robust biofilm development, which represents another major virulence factor for candidiasis and further complicates treatment. Targeting pathogenic mechanisms rather than growth represents an attractive yet clinically unexploited approach in the development of novel antifungal agents. Here, we performed large-scale phenotypic screening assays with 30,000 drug-like small-molecule compounds within ChemBridge’s DIVERSet chemical library in order to identify small-molecule inhibitors of C. albicans filamentation, and our efforts led to the identification of a novel series of bioactive compounds with a common biaryl amide core structure. The leading compound of this series, N-[3-(allyloxy)-phenyl]-4-methoxybenzamide, was able to prevent filamentation under all liquid and solid medium conditions tested, suggesting that it impacts a common core component of the cellular machinery that mediates hypha formation under different environmental conditions. In addition to filamentation, this compound also inhibited C. albicans biofilm formation. This leading compound also demonstrated in vivo activity in clinically relevant murine models of invasive and oral candidiasis. Overall, our results indicate that compounds within this series represent promising candidates for the development of novel anti-virulence approaches to combat C. albicans infections. PMID:29208749
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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.
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Majdabadi, Niloufar; Falahati, Mehraban; Heidarie-Kohan, Fariba; Farahyar, Shirin; Rahimi-Moghaddam, Parvaneh; Ashrafi-Khozani, Mahtab; Razavi, Tandis; Mohammadnejad, Sina
2018-04-01
The antifungal effects of 2-phenylethanol are clearly visible through its intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis, however, does not respond to this standard experimental therapy; therefore, the study presented in this article investigated the effect of common antifungal drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in combination with 2-phenylethanol, on the Candida species isolated from cases of chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a more appropriate treatment option. Forty isolates from patients with chronic and recurrent vaginal candidiasis were investigated in this experimental study. The specimens were examined by direct microscopy, culturing, and PCR to identify the species. The antifungal effects of 2-phenylethanol and conventional drugs, both alone and in combination, were determined in duplicate. Finally, the findings were analyzed. In this study, 40 strains of Candida species were identified, whose agents were Candida albicans (95%) and Candida africana (5%). After 48 h, the minimum inhibitory concentration (MIC) range of the 2-phenylethanol was 800-3,200 μg/mL. Also, in the final study on the MIC levels of common antifungal drugs, AMB (0.42 μg/mL) had the lowest MIC, FLU (40.51 μg/mL) had the highest MIC, and the combination of ITC and 2-phenylethanol had the lowest fractional inhibitory concentration index (FICI) of any of the combinations (FICI range, 0.26-1.03). Combining FLU and ITC with 2-phenylethanol can effectively increase their antifungal effect.
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Luliconazole, an alternative antifungal agent against Aspergillus terreus.
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.
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Antifungal activities of ethanolic extract from Jatropha curcas seed cake.
Saetae, Dolaporn; Suntornsuk, Worapot
2010-02-01
Phorbol ester extraction was carried out from Jatropha curcas seed cake, a by-product from the bio-diesel fuel industry. Four repeated extractions from 5 g J. curcas seed cake using 15 ml of 90% (v/v) ethanol and a shaking speed of 150 rev/min gave the highest yield of phosbol esters. The ethanolic extract of J. curcas seed cake showed antifungal activities against important phytofungal pathogens: Fusarium oxysporum, Pythium aphanidermatum, Lasiodiplodia theobromae, Curvularia lunata, Fusarium semitectum, Colletotrichum capsici and Colletotrichum gloeosporiodes. The extract contained phorbol esters mainly responsible for antifungal activities. The extract could therefore be used as an antifungal agent for agricultural applications.
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Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.
Santos, Karla K.A.; Matias, Edinardo F.F.; Tintino, Saulo R.; Souza, Celestina E.S.; Braga, Maria F.B.M.; Guedes, Gláucia M.M.; Costa, José G.M.; Menezes, Irwin R.A.
2013-01-01
Abstract Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641
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Mixtures of Quaternary Ammonium Compounds and Long-chain Fatty Acids as Antifungal Agents
Kull, F. C.; Eisman, P. C.; Sylwestrowicz, H. D.; Mayer, R. L.
1961-01-01
The influence of undecylenic acid on the fungistatic effect of phenoxyethyldimethyldodecylammonium bromide (Domiphen bromide) against Trichophyton mentagrophytes was investigated. The unsaturated fatty acid was found to enhance the fungistatic activity of Domiphen bromide against this organism. The ratio of concentrations of these agents has a marked influence on the results of in vitro tests for antifungal action resulting in a completely different effect than heretofore noted in combination experiments against bacteria. The enhancing phenomenon is not particular to T. mentagrophytes, it was observed also with Candida albicans. PMID:14460466
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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
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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.
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Antifungal effects of phytocompounds on Candida species alone and in combination with fluconazole.
Lu, Mengjiao; Li, Tao; Wan, Jianjian; Li, Xiuyun; Yuan, Lei; Sun, Shujuan
2017-02-01
Invasive fungal infections caused by Candida spp. remain the most predominant nosocomial fungal infections. Owing to the increased use of antifungal agents, resistance of Candida spp. to antimycotics has emerged frequently, especially to fluconazole (FLC). To cope with this issue, new efforts have been dedicated to discovering novel antimycotics or new agents that can enhance the susceptibility of Candida spp. to existing antimycotics. The secondary metabolites of plants represent a large library of compounds that are important sources for new drugs or compounds suitable for further modification. Research on the anti-Candida activities of phytocompounds has been carried out in recent years and the results showed that a series of phytocompounds have anti-Candida properties, such as phenylpropanoids, flavonoids, terpenoids and alkaloids. Among these phytocompounds, some displayed potent antifungal activity, with minimum inhibitory concentrations (MICs) of ≤8 µg/mL, and several compounds were even more effective against drug-resistant Candida spp. than FLC or itraconazole (e.g. honokiol, magnolol and shikonin). Interestingly, quite a few phytocompounds not only displayed anti-Candida activity alone but also synergised with FLC against Candida spp., even leading to a reversal of FLC resistance. This review focuses on summarising the anti-Candida activities of phytocompounds as well as the interactions of phytocompounds with FLC. In addition, we briefly overview the synergistic mechanisms and present the structure of the antimycotic phytocompounds. Hopefully, this analysis will provide insight into antifungal agent discovery and new approaches against antifungal drug resistance. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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Fungal infections of the eye--laboratory diagnosis and treatment.
Nayak, N
2008-03-01
Infections of the eye give rise to severe ocular morbidity and blindness include keratitis, orbital cellulites, endophthalmitis and dacryocystitis. Corneal blindness, in developing countries is predominantly associated with infections. In India, nearly 30-35% of all culture positive infectious keratitis are caused fungi. Laboratory diagnosis mainly depends upon proper collection and transport of clinical specimens. In fungal keratitis, corneal scraping is the ideal sample, but occasionally corneal biopsy or anterior chamber aspirate may also be needed. Corneal scraping is usually by Kimura spatula, under a slit lamp examination, after anaesthetizing the cornea with topical anaesthetic like 0.4% proparcaine. Corneal biopsy is done by a minor trephining and AC aspirate using a sterile tuberculin syringe. In case of endophthalmitis, 150-200 ìl of aqueous humour is collected. Vitreous fluid (500-1000 ìl), however, is collected by pars plana vitrectomy onto sterile tuberculin syringe, the needle is then fixed to a sterile rubber bung after expelling air from the syringe. The collected sample is immediately transported to the laboratory. Swabs from the regurgitating lacrimnal sacs and wound aspirate/swabs are the ideal specimens for dacryocystitis and orbital cellulites, respectively. These samples are cultured onto SDA slants following standard procedures. The main draw back of culture is its long incubation time (5 to 14 days), though it is indispensable from the view point of the specificity. Direct examination (KOH wet mount, Gram's, Giemsa or calcofluor fluorescent staining methods) of the specimen, however, is quick and immensely helpful for ophthalmologist. The newer rapid methods, such as molecular techniques are also available and the management of patients can be according to the results obtained. With the advent of novel antifungal agents such as newer azoles and cell wall acting antifungals like echinocandins, the clinician has the wider option of selecting the therapeutic modality. In the event of the increasing reports of in vitro drug resistance to much frequently used azoles, polyenes and 5-fluorocytosines, clinical applicability of the newer antifungal agents seems to be quite promising.
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Antifungal activity of medicinal plant extracts; preliminary screening studies.
Webster, Duncan; Taschereau, Pierre; Belland, René J; Sand, Crystal; Rennie, Robert P
2008-01-04
In the setting of HIV and organ transplantation, opportunistic fungal infections have become a common cause of morbidity and mortality. Thus antifungal therapy is playing a greater role in health care. Traditional plants are a valuable source of novel antifungals. To assess in vitro antifungal activity of aqueous plant extracts. The minimum inhibitory concentrations were determined for each extract in the setting of human pathogenic fungal isolates. Plants were harvested and identification verified. Aqueous extracts were obtained and antifungal susceptibilities determined using serial dilutional extracts with a standardized microdilution broth methodology. Twenty-three fungal isolates were cultured and exposed to the plant extracts. Five known antifungals were used as positive controls. Results were read at 48 and 72 h. Of the 14 plants analyzed, Fragaria virginiana Duchesne, Epilobium angustifolium L. and Potentilla simplex Michx. demonstrated strong antifungal potential overall. Fragaria virginiana had some degree of activity against all of the fungal pathogens. Alnus viridis DC., Betula alleghaniensis Britt. and Solidago gigantea Ait. also demonstrated a significant degree of activity against many of the yeast isolates. Fragaria virginiana, Epilobium angustifolium and Potentilla simplex demonstrate promising antifungal potential.
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Zhao, Fei; Dai, Jiang-Kun; Liu, Dan; Wang, Shi-Jun; Wang, Jun-Ru
2016-03-21
As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 μg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 μg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents.
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Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs
Shan, T.; Ma, Q.; Guo, K.; Liu, J.; Li, W.; Wang, F.; Wu, E.
2011-01-01
Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent. PMID:21902651
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[Invasive mould disease in haematological patients].
Ruiz-Camps, Isabel; Jarque, Isidro
2014-01-01
Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper. Copyright © 2014. Published by Elsevier Espana.
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García Heredia, M; García, S D; Copolillo, E F; Cora Eliseth, M; Barata, A D; Vay, C A; de Torres, R A; Tiraboschi, N; Famiglietti, A M R
2006-01-01
Pregnant women are more susceptible to both vaginal colonization and infection by yeast. Our objectives were to determine the prevalence in pregnant women of yeasts isolated from vaginal exudates and their susceptibility to current antifungal drugs. A total of 493 patients was studied between December 1998 and February 2000. The prevalence of Candida spp. was 28% (Candida albicans 90.4%; Candida glabrata 6.3%; Candida parapsilosis 1.1%, Candida kefyr 1.1 %; unidentified species 1.1 %). The diffusion test in Shadomy agar was employed to determine the susceptibility to fluconazole, ketoconazole, itraconazole and nistatine. All C. albicans, C. kefyr and C. parapsilosis isolates were susceptible in vitro to the antifungal agents tested, while 1 in 6 C. glabrata isolates showed resistance to azole drugs; all strains were susceptible to nistatine. In pregnant women, C. albicans was the yeast most frequently isolated from vaginal exudates; it continues to be highly susceptible to antifungal drugs. Azole resistance was detected only among C. glabrata isolates. Identification to the species level is recommended, specially in cases of treatment failure and recurrent or chronic infection.
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Büchner, T; Fegeler, W; Bernhardt, H; Brockmeyer, N; Duswald, K-H; Herrmann, M; Heuser, D; Jehn, U; Just-Nübling, G; Karthaus, M; Maschmeyer, G; Müller, F-M; Müller, J; Ritter, J; Roos, N; Ruhnke, M; Schmalreck, A; Schwarze, R; Schwesinger, G; Silling, G
2002-05-01
Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.
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Quercetin and rutin as potential agents antifungal against Cryptococcus spp.
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.
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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.
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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
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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.
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Amphotericin B-silver hybrid nanoparticles: synthesis, properties and antifungal activity.
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.
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NASA Astrophysics Data System (ADS)
Sidhu, Anjali; Ghatelwal, Suman R.; Gumber, Khushbu; Bala, Anju
2017-11-01
This study was focused on the preparation of benzothiazol-2-ylcarbamodithioates-silver nanoconjugates (BCDTC-AgNPs) for their in vitro antifungal evaluation against various phytopathogenic fungi viz. Pyricularia grisea, Drechslera oryzae, Fusarium moniliforme and Ustilaginoidea virens. Benzothiazol-2-ylcarbamodithioates (BCDTCs) were used both as capping as well as stabilizing for silver nanoparticles (AgNPs). The prepared nanoconjugates were analysed by UV-visible and TEM studies. The comparative antifungal evaluation of BCDTC-AgNPs with precursor BCDTCs and AgNPs indicated the manifold increase in antifungal potential when applied as nanoconjugates. The promising results were comparable to the standard commercial fungicides Tilt and Bavistin, in most of the cases.
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Thangamani, Shankar; Eldesouky, Hassan E; Mohammad, Haroon; Pascuzzi, Pete E; Avramova, Larisa; Hazbun, Tony R; Seleem, Mohamed N
2017-01-01
Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen. Ebselen's antifungal activity in vivo was investigated in a Caenorhabditis elegans animal model. Ebselen exhibits potent antifungal activity against both Candida spp. and Cryptococcus spp., at concentrations ranging from 0.5 to 2μg/ml. Ebselen rapidly eradicates a high fungal inoculum within 2h of treatment. Investigation of the drug's antifungal mechanism of action indicates that ebselen depletes intracellular glutathione (GSH) levels, leading to increased production of reactive oxygen species (ROS), and thereby disturbs the redox homeostasis in fungal cells. Examination of ebselen's in vivo antifungal activity in two Caenorhabditis elegans models of infection demonstrate that ebselen is superior to conventional antifungal drugs (fluconazole, flucytosine and amphotericin) in reducing Candida and Cryptococcus fungal load. Ebselen possesses potent antifungal activity against clinically relevant isolates of both Candida and Cryptococcus by regulating GSH and ROS production. The potent in vivo antifungal activity of ebselen supports further investigation for repurposing it for use as an antifungal agent. The present study shows that ebselen targets glutathione and also support that glutathione as a potential target for antifungal drug development. Copyright © 2016 Elsevier B.V. All rights reserved.
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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.
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Antifungal Microbial Agents for Food Biopreservation—A Review
Leyva Salas, Marcia; Mounier, Jérôme; Coton, Monika; Thierry, Anne; Coton, Emmanuel
2017-01-01
Food spoilage is a major issue for the food industry, leading to food waste, substantial economic losses for manufacturers and consumers, and a negative impact on brand names. Among causes, fungal contamination can be encountered at various stages of the food chain (e.g., post-harvest, during processing or storage). Fungal development leads to food sensory defects varying from visual deterioration to noticeable odor, flavor, or texture changes but can also have negative health impacts via mycotoxin production by some molds. In order to avoid microbial spoilage and thus extend product shelf life, different treatments—including fungicides and chemical preservatives—are used. In parallel, public authorities encourage the food industry to limit the use of these chemical compounds and develop natural methods for food preservation. This is accompanied by a strong societal demand for ‘clean label’ food products, as consumers are looking for more natural, less severely processed and safer products. In this context, microbial agents corresponding to bioprotective cultures, fermentates, culture-free supernatant or purified molecules, exhibiting antifungal activities represent a growing interest as an alternative to chemical preservation. This review presents the main fungal spoilers encountered in food products, the antifungal microorganisms tested for food bioprotection, and their mechanisms of action. A focus is made in particular on the recent in situ studies and the constraints associated with the use of antifungal microbial agents for food biopreservation. PMID:28698479
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Antifungal Microbial Agents for Food Biopreservation-A Review.
Leyva Salas, Marcia; Mounier, Jérôme; Valence, Florence; Coton, Monika; Thierry, Anne; Coton, Emmanuel
2017-07-08
Food spoilage is a major issue for the food industry, leading to food waste, substantial economic losses for manufacturers and consumers, and a negative impact on brand names. Among causes, fungal contamination can be encountered at various stages of the food chain (e.g., post-harvest, during processing or storage). Fungal development leads to food sensory defects varying from visual deterioration to noticeable odor, flavor, or texture changes but can also have negative health impacts via mycotoxin production by some molds. In order to avoid microbial spoilage and thus extend product shelf life, different treatments-including fungicides and chemical preservatives-are used. In parallel, public authorities encourage the food industry to limit the use of these chemical compounds and develop natural methods for food preservation. This is accompanied by a strong societal demand for 'clean label' food products, as consumers are looking for more natural, less severely processed and safer products. In this context, microbial agents corresponding to bioprotective cultures, fermentates, culture-free supernatant or purified molecules, exhibiting antifungal activities represent a growing interest as an alternative to chemical preservation. This review presents the main fungal spoilers encountered in food products, the antifungal microorganisms tested for food bioprotection, and their mechanisms of action. A focus is made in particular on the recent in situ studies and the constraints associated with the use of antifungal microbial agents for food biopreservation.
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Ahmad, Aftab; Wei, Yun; Syed, Fatima; Tahir, Kamran; Taj, Raheela; Khan, Arif Ullah; Hameed, Muhammad Usman; Yuan, Qipeng
2016-10-01
New strategies are required to improve the efficacy of drugs and to treat the emerging microbial resistance. An effective strategy is to combine drugs with metal nanoparticles for the control of microbial infections and resistance. Keeping in view this fact, we developed a facile and eco-friendly protocol for the synthesis of amphotericin B-conjugated silver nanoparticles and their assessment as an antifungal agent. Phytochemicals from the aqueous extract of Maytenus royleanus and amphotericin B were used as capping agents to prepare two types of silver nanoparticles i.e. (i) biogenic silver nanoparticles (b-AgNPs) and (ii) amphotericin B-conjugated biogenic silver nanoparticles (Amp-bAgNPs). UV-Vis spectroscopy was used to detect the characteristic surface Plasmon resonance peaks (SPR) for the prepared nanoparticles (424-433 nm). High-resolution transmission electron microscopy (HRTEM) study revealed the formation of well dispersed and spherical silver nanoparticles and Amp-bAgNPs with an average particles size of 10 and 15 nm. EDX and FTIR studies confirmed the elemental composition and surface adhered biomolecules in the prepared nanoparticles respectively. Biogenic silver nanoparticles revealed low to moderate antifungal activity (4-8 mm ± 0.2), however, the amphotericin B conjugated silver nanoparticles exhibited significant activity against Candida albicans (16 mm ± 1.4) and Candida tropicalis (18 mm ± 1.5). In conclusion, the enhanced antifungal activity of the Amp-AgNPs conjugate system is due to the synergy between the antifungal activity of amphotericin B and the antimicrobial property of silver. The findings of this study suggest that the conjugated nanoparticles could be used as efficient antifungal agents and drug delivery vehicles. Furthermore, this is the first report describing the synthesis of silver nanoparticles using the aqueous extract of Maytenus royleanus and the conjugation of amphotericin B, an antifungal drug, to the phytosynthesized silver nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.
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[Fungal infectivities of implanted catheters due to Candida sp. Biofilms formation and resistance].
Seddiki, S M L; Boucherit-Otmani, Z; Boucherit, K; Kunkel, D
2015-06-01
Candidemia are the most common fungal infections in hospitals. However, the catheters are subject to be altered by Candida biofilms which increase the risk of invasive nosocomial infections due to the high resistance to antifungal agents. Therefore, the minimum inhibitory concentrations of planktonic (MIC) and sessile cells (CIMS) were evaluated. To review the in vivo biofilms structures of Candida sp. formed on the inner and/or external surfaces of collected catheters, we used scanning electron microscopy (SEM). The level of biofilm resistance was assessed against two conventional antifungal agents: amphotericin B (AmB), which belongs to the class of polyenes, and fluconazole (FLZ) which is an azole. The SEM observation of biofilms of Candida sp. reveals complex structures. Compared to MICs, the calculation of CIMS showed an increase of 32 times with AmB and of 128 times with FLZ. Catheters offer an ideal surface to Candida sp. to form biofilms. This complex structure induces the increase of the resistance of sessile cells against two antifungal agents, AmB and FLZ. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Butts, Arielle; Martin, Jennifer A.; DiDone, Louis; Bradley, Erin K.; Mutz, Mitchell; Krysan, Damian J.
2015-01-01
Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold. PMID:26016941
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Vallejo, Carlos; Vázquez, Lourdes; Cabrera Martín, José Rafael; Carreras, Enric; García Rodríguez, Julio; Ruiz Camps, Isabel; Fortún, Jesús; Mensa, Josep; Barberán, José
2013-12-01
Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.
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Kavakçıoğlu, Berna; Tarhan, Leman
2018-01-01
Clotrimazole is an antifungal medication commonly used in the treatment of fungal infections. There is also promising research on using clotrimazole against other diseases such as malaria, beriberi, tineapedis and cancer. It was aimed to investigate the apoptotic phenotype in Saccharomyces cerevisiae induced by clotrimazole. The exposure of S. cerevisiae to 10 µM clotrimazole for 3, 6 and 9 h caused to decrease in cell viability by 24.82 ± 0.81, 56.00 ± 1.54 and 77.59 ± 0.53%, respectively. It was shown by Annexin V-PI assay that 110 µM clotrimazole treatment caused to death by 35.5 ± 2.48% apoptotic and only 13.1 ± 0.08% necrotic pathway within 30 min. The occurrence of DNA strand breaks and condensation could be visualised by the TUNEL and DAPI stainings, respectively. Yeast caspase activity was induced 12.34 ± 0.71-fold after 110 µM clotrimazole treatment for 30 min compared to the control. The dependency of clotrimazole-induced apoptosis to caspase was also shown using Δyca1 mutant.
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Evaluation of the antifungal effect of EDTA, a metal chelator agent, on Candida albicans biofilm.
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.
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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
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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.
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Patel, Navin B; Patel, Jignesh N; Purohit, Amit C; Patel, Vatsal M; Rajani, Dhanji P; Moo-Puc, Rosa; Lopez-Cedillo, Julio Cesar; Nogueda-Torres, Benjamin; Rivera, Gildardo
2017-09-01
A new series of N-(substituted-phenyl)-2-[5-(quinoxalin-2-yloxymethyl)-[1,3,4] oxadiazol-2-ylsulfanyl]-acetamides (5a-o) was designed and synthesised from the parent compound 2-hydroxy quinoxaline (1) through a multistep reaction sequence and was characterised by spectral and elemental analyses. All of the compounds synthesised were evaluated for their antimicrobial and antiprotozoal activities. The results revealed that quinoxaline-based 1,3,4-oxadiazoles displayed promising antibacterial, antifungal and anti-Trypanosoma cruzi activities compared with reference drugs, particularly the lead compound 5l in a short-term in vivo model in T. cruzi. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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Recent studies on the antimicrobial peptides lactoferricin and lactoferrampin.
Yin, C; Wong, J H; Ng, T B
2014-01-01
Lactoferricin and lactoferrampin, peptides derived from the whey protein lactoferrin, are antimicrobial agents with a promising prospect and are currently one of the research focuses. In this review, a basic introduction including location and solution structures of these two peptides is given. Their biological activities encompassing antiviral, antibacterial, antifungal and anti-inflammatory activities with possible mechanisms are mentioned. In terms of modification studies, research about identification of their active derivatives and crucial amino acid residues is also discussed. Various attempts at modification of lactoferricin and lactoferrampin such as introducing big hydrophobic side-chains; employing special amino acids for synthesis; N-acetylization, amidation, cyclization and peptide chimera are summarized. The studies on lactoferricin-lactoferrampin chimera are discussed in detail. Future prospects of lactoferricin and lactoferrampin are covered.
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Ogunshe, Adenike A O; Adepoju, Adedayo A; Oladimeji, Modupe E
2011-01-01
This study aimed at evaluating the in vitro efficacy and health implications of inconsistencies in different production batches of antimycotic drugs. in vitro susceptibility profiles of 36 Candida spp. - C. albicans (19.4%), C. glabrata (30.6%), C. tropicalis (33.3%), and C. pseudotropicalis (16.7%) - obtained from human endocervical and high vaginal swabs (ECS/HVS) to two different batches (B1 and B2) of six antimycotic drugs (clotrimazole, doxycycline, iconazole, itraconazole, metronidazole and nystatin) was determined using modified agar well-diffusion method. None of the Candida strains had entirely the same (100%) susceptibility / resistance profiles in both batches of corresponding antimycotic drugs; while, different multiple antifungal susceptibility (MAS) rates were also recorded in batches 1 and 2 for corresponding antifungals. Only 14.3%, 27.3%, 16.7-33.3%, and 8.3-25.0% of C. albicans, C. glabrata, C. pseudotropicalis, and C. tropicalis strains, respectively, had similar susceptibility/resistance profiles toward coressponding antifungal agents in both batches; while up to 57.1% of C. albicans, 45.5% of C. glabrata, 66.7% of C. pseudotropicalis, and 50.0% of C. tropicalis strains were susceptible to one batch of antifungals but resistant to corresponding antifungals in the second batch. As high as 71.4% (C. albicans), 73.0% (C. glabrata), 50.0% (C. pseudotropicalis), and 66.74% (C. tropicalis) strains had differences of ≥ 10.0 mm among corresponding antimycotic agents. Candida strains exhibited different in vitro susceptibility / resistance patterns toward two batches of corresponding antimycotic agents, which has clinical implications on the efficacy of the drugs and treatment of patients. The findings of the present study will be of benefit in providing additional information in support of submission of drugs for registration to appropriate regulatory agencies.
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Nishiyama, Yayoi; Takahata, Sho; Abe, Shigeru
2017-01-01
The effects of ME1111, a novel antifungal agent, on the hyphal morphology and ultrastructure of Trichophyton mentagrophytes were investigated by using scanning and transmission electron microscopy. Structural changes, such as pit formation and/or depression of the cell surface, and degeneration of intracellular organelles and plasmolysis were observed after treatment with ME1111. Our results suggest that the inhibition of energy production by ME1111 affects the integrity and function of cellular membranes, leading to fungal cell death. Copyright © 2016 American Society for Microbiology.
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P&T Committee review of fluconazole: an effective alternative to antifungal therapy.
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.
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[Cutaneous Malassezia infections and Malassezia associated dermatoses: An update].
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.
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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.
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Mina, John G M; Denny, P W
2018-02-01
Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.
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In vitro pyrogen test for toxic or immunomodulatory drugs.
Daneshian, Mardas; Guenther, Armin; Wendel, Albrecht; Hartung, Thomas; von Aulock, Sonja
2006-06-30
Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After rinsing, the beads are incubated with human whole blood and the release of the endogenous pyrogen interleukin-1beta is measured as a marker of pyrogenic activity. Intentional contaminations with lipopolysaccharide were retrieved from the chemotherapeutic agents paclitaxel, cisplatin and liposomal daunorubicin, the antibiotic gentamicin, the antifungal agent liposomal amphotericin B, and the corticosteroid prednisolone at lower dilutions than in the standard in vitro pyrogen test. This represents a promising new approach for the detection of pyrogenic contamination in drugs or in drugs containing interfering additives and should lead to improved safety levels.
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NASA Astrophysics Data System (ADS)
Pourjavadi, Ali; Soleyman, Rouhollah
2011-10-01
In the current study, a facile green synthesis of silver-gelatin core-shell nanostructures (spherical, spherical/cubic hybrid, and cubic, DLS diameter: 4.1-6.9 nm) is reported via the wet chemical synthesis procedure. Sunlight-UV as an available reducing agent cause mild reduction of silver ions into the silver nanoparticles (Ag-NPs). Gelatin protein, as an effective capping/shaping agent, was used in the reaction to self-assemble silver nanostructures. The formation of silver nanostructures and their self-assembly pattern was confirmed by SEM, AFM, and TEM techniques. Further investigations were carried out using zeta-potential, UV-Vis, FTIR, GPC, and TGA/DTG/DTA data. The prepared Ag-NPs showed proper and acceptable antimicrobial activity against three classes of microorganisms ( Escherichia coli Gram-negative bacteria, Staphylococcus aureus Gram-positive bacteria, and Candida albicans fungus). The antibacterial and antifungal Ag-NPs exhibit good stability in solution and can be considered as promising candidates for a wide range of biomedical applications.
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Gamaletsou, Maria N.; Walsh, Thomas J.; Sipsas, Nikolaos V.
2018-01-01
Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance. PMID:29391334
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Butts, Arielle; Reitler, Parker; Ge, Wenbo; Fortwendel, Jarrod R; Palmer, Glen E
2018-04-30
The incidence of invasive fungal infections has risen significantly in recent decades as medical interventions have become increasingly aggressive. These infections are extremely difficult to treat due to the extremely limited repertoire of systemic antifungals, the development of drug resistance, and the extent of to which the patient's immune function is compromised. Even when the appropriate antifungal therapies are administered in a timely fashion, treatment failure is common, frequently even in the absence of in vitro microbial resistance. In this study, we screened a small collection of FDA approved oncolytic agents for compounds that impact the efficacy of the two most widely used classes of system antifungals against Candida albicans, Candida glabrata , and Aspergillus fumigatus We have identified several drugs that enhance fungal growth in the presence of the azole antifungals and examine the potential that these drugs directly affect fungal fitness, specifically antifungal susceptibility, and may be contributing to clinical treatment failure. Copyright © 2018 American Society for Microbiology.
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Chaturvedi, Ashok K.; Rozental, Sonia
2015-01-01
The generation of a new antifungal against Candida albicans biofilms has become a major priority, since biofilm formation by this opportunistic pathogenic fungus is usually associated with an increased resistance to azole antifungal drugs and treatment failures. Miltefosine is an alkyl phospholipid with promising antifungal activity. Here, we report that, when tested under planktonic conditions, miltefosine displays potent in vitro activity against multiple fluconazole-susceptible and -resistant C. albicans clinical isolates, including isolates overexpressing efflux pumps and/or with well-characterized Erg11 mutations. Moreover, miltefosine inhibits C. albicans biofilm formation and displays activity against preformed biofilms. Serial passage experiments confirmed that miltefosine has a reduced potential to elicit resistance, and screening of a library of C. albicans transcription factor mutants provided additional insight into the activity of miltefosine against C. albicans growing under planktonic and biofilm conditions. Finally, we demonstrate the in vivo efficacy of topical treatment with miltefosine in the murine model of oropharyngeal candidiasis. Overall, our results confirm the potential of miltefosine as a promising antifungal drug candidate, in particular for the treatment of azole-resistant and biofilm-associated superficial candidiasis. PMID:26416861
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Martins, Margarida; Henriques, Mariana; Lopez-Ribot, José L.; Oliveira, Rosário
2011-01-01
SUMMARY Background Cells within Candida albicans biofilms display decreased susceptibility to most clinically used antifungal agents. We recently demonstrated that extracellular DNA (eDNA) plays an important role in biofilm integrity, as a component of the biofilm matrix. Objective To gain insight into the contributions of eDNA to C. albicans biofilms antifungal susceptibility by the investigation of the impact of the combined use of deoxyribonuclease I (DNase) and antifungals to treat biofilms. Methods C. albicans biofilms were formed using a simple and reproducible 96-well plate-based method. The activity of the combined use of 0.13 mg l−1 DNase and antifungals was estimated by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay, and total viable counts. Results and Conclusions Here we report the improved efficacy of amphotericin B when in combination with DNase against C. albicans biofilms, as assessed by XTT readings and viable counts. Furthermore, although DNase increased the efficacy of caspofungin in the reduction of mitochondrial activity, no changes were observed in terms of culturable cells. DNase did not affect biofilm cells susceptibility to fluconazole. This work suggests that agents that target processes affecting the biofilm structural integrity may have potential use as adjuvants of a catheter–lock therapy. PMID:21668524
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[Susceptibility to antifungal agents of Candida sp. and biofilm formation].
Ciok-Pater, Emilia; Białucha, Agata; Gospodarek, Eugenia; Ostafin, Agnieszka
2011-01-01
In recent years the increase in frequency of fungal infections with Candida sp. was noticed. These infections are connected with ability of Candida sp. to form biofilm on surfaces of biomaterials used in medicine. Furthermore fungal infections make serious therapeutic problems because ofbiofilm resistance to antifungal agents actually. The aim of the study was to evaluate the susceptibility to antifungal agents of Candida sp. and their ability to form biofilm on different biomaterials. 50 strains of Candida sp. isolated from patients of University Hospital No. 1 of dr A. Jurasz in Bydgoszcz were examined. API Candida (bioMérieux) tests were used to identify Candida sp. strains. The susceptibility of the yeast strains to antifungal agents was evaluated by ATB FUNGUS 2 INT (bioMérieux) tests. The susceptibility of examined strains to voriconazole, posaconazole, caspofungin and anidulafungin was assessed by means ofEtests (AB BIODISK) method employing drug concentrations from 0,002 to 32 microg/ml. All analysed strains were susceptible to amphotericin B and caspofungin. Biofilm formation on different biomaterials (silicon, latex, polychloride vinyl, polypropylene, nylon) was measured after 72 hour incubation at 37 degrees C. All examined yeasts formed biofilm on all analysed biomaterials. The highest number of strains formed biofilm on surface of polychloride vinyl: 23 (92,0%) by C. albicans strains and 24 (96,0%) Candida non-albicans strains. The lowest number of the strains formed biofilm on the surface of nylon: 12 (48,0%) of C. albicans strains and 9 (36,0%) of Candida non-albicans strains. The studied strains resistant to azoles and anidulafungin display stronger ability to form biofilm on surfaces of all analysed biomaterials.
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Al-Shayyab, Mohammad H; Abu-Hammad, Osama A; Al-Omiri, Mahmoud K; Dar-Odeh, Najla S
2015-08-01
The aim of this study was to evaluate the attitude of Jordanian dentists towards the treatment of oral candidiasis and their current antifungal prescribing habits, shedding more light on the possible influence of their socio-professional factors on the pattern of prescribing and practice. A structured validated questionnaire was developed and tested; it was then emailed to a random sample of 600 Jordanian dental practitioners during the period of this cross-sectional survey. The questionnaire recorded practitioners' personal details and their attitude and prescribing of antifungal therapy for oral candidiasis. Statistical significance was based on probability values of <0.05 and was measured using the chi-square and Fisher's exact tests. Multiple logistic regression analysis was used to analyse the influence of respondents' socio-professional factors on their attitude towards oral candidiasis. Of the 423 questionnaires returned, only 330 were included. The attitude of respondents was significantly influenced by their experience [odds ratio (OR) = 0.14; P < 0.001] and workplace (OR = 4.70; P < 0.001). Nystatin was the most commonly prescribed antifungal agent (78.2%), followed by miconazole (62.4%), which was prescribed for topical use. Systemic antifungals were prescribed by 21.2% of respondents, with a significant (P < 0.05) association with the country in which their qualification was obtained. The attitude towards the treatment of oral candidiasis is much better among the least-experienced dentists working in private practice. Nystatin and miconazole are the most popular choices of antifungal agents among Jordanian dentists. © 2015 FDI World Dental Federation.
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Hou, Zhe; Zhu, Li-Fei; Yu, Xin-chi; Sun, Ma-Qiang; Miao, Fang; Zhou, Le
2016-04-13
Twenty-two 2-aryl-9-methyl-3,4-dihydro-β-carbolin-2-ium bromides along with four 9-demethylated derivatives were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Almost all of the compounds showed obvious inhibition activity on each of the fungi at 150 μM. For all of the fungi, 10 of the compounds showed average inhibition rates of >80% at 150 μM, and most of their EC50 values were in the range of 2.0-30.0 μM. SAR analysis showed that the substitution pattern of the N-aryl ring significantly influences the activity; N9-alkylation improves the activity, whereas aromatization of ring-C reduces the activity. It was concluded that the present research provided a series of new 2-aryl-9-alkyl-3,4-dihydro-β-carbolin-2-iums with excellent antifungal potency and structure optimization design for the development of new carboline antifungal agents.
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Antifungal and antioxidant activities of mature leaves of Myrcia splendens (Sw.) DC.
Pontes, F C; Abdalla, V C P; Imatomi, M; Fuentes, L F G; Gualtieri, S C J
2018-05-07
In recent years, natural products with antifungal and antioxidant activities are being increasingly researched for a more sustainable alternative to the chemicals currently used for the same purpose. The plant pathogenic fungus Alternaria alternata is a causative agent of diseases in citrus, leading to huge economic losses. Antioxidants are important for the production of medicines for various diseases that may be related to the presence of free radicals, such as cancer, and in the cosmetic industry as an anti-aging agent and the food industry as preservatives. This study evaluated the antifungal and antioxidant potential of extracts of mature leaves of Myrcia splendens, a tree species that occurs in the Brazilian Cerrado. The antioxidant potential was analyzed by an assay of 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method, and the antifungal activity was assessed through the evaluation of mycelial growth. Majority of the extracts exhibited a strong antioxidant activity, especially the acetonic extract (4A). The antioxidant activity may be related to the presence of phenolic compounds. However, the extracts showed no inhibitory activity of mycelial growth of the fungus tested, with the exception of dichloromethanic extract (2B), which had an inhibitory effect (10.2%) at the end of testing.
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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.
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Synthesis and QSAR study of novel α-methylene-γ-butyrolactone derivatives as antifungal agents.
Wu, Yong-Ling; Wang, De-Long; Guo, En-Hui; Song, Shuang; Feng, Jun-Tao; Zhang, Xing
2017-03-01
Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC 50 ) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC 50 =22.91, 18.89μM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R 2 =0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC 50 =18.89μM (against B. cinerea.) but low cytotoxicity with IC 50 =35.4μM (against HepG2 cell line) and IC 50 =68.8μM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Lima, Valéria N; Oliveira-Tintino, Cícera D M; Santos, Enaide S; Morais, Luís P; Tintino, Saulo R; Freitas, Thiago S; Geraldo, Yuri S; Pereira, Raimundo L S; Cruz, Rafael P; Menezes, Irwin R A; Coutinho, Henrique D M
2016-10-01
The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 μg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 μg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 μg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action. Copyright © 2016 Elsevier Ltd. All rights reserved.
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[Onychocola canadensis Sigler in onychomycosis : A new dermatophyte-like mould in Germany].
Nenoff, P; Schorlemmer, B; Uhrlaß, S; Baunacke, A; Baunacke, A; Friedrichs, C; Iffländer, J; Syhre, E; Schneider, A; Krüger, C; Maier, T
2016-09-01
Moulds or non-dermatophyte moulds (NDM) are being increasingly isolated as causative agent of onychomycoses. Known causes of a NDM-OM are Scopulariopsis brevicaulis, Fusarium, Aspergillus, Acremonium, Neoscytalidium dimidiatum, Arthrographis kalrae, and Chaetomium. In this article, 5 patients with suspected nail infection due to Onychocola canadensis are reported for the first time in Germany. Systemic antifungal agents are not considered to be effective in NDM onychomycosis. In individual cases, however, terbinafine seems to be effective in Onychocola canadensis infection of the nails. Treatment of choice represents, however, nontraumatic nail avulsion using 40 % urea ointment followed by antifungal nail lacquer with ciclopirox olamine or amorolfine.
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Rank, Leslie A.; Walsh, Naomi M.; Lim, Fang Yun
2018-01-01
ABSTRACT Understanding the dimensions of fungal diversity has major implications for the control of diseases in humans, plants, and animals and in the overall health of ecosystems on the planet. One ancient evolutionary strategy organisms use to manage interactions with microbes, including fungi, is to produce host defense peptides (HDPs). HDPs and their synthetic analogs have been subjects of interest as potential therapeutic agents. Due to increases in fungal disease worldwide, there is great interest in developing novel antifungal agents. Here we describe activity of polymeric HDP analogs against fungi from 18 pathogenic genera composed of 41 species and 72 isolates. The synthetic polymers are members of the nylon-3 family (poly-β-amino acid materials). Three different nylon-3 polymers show high efficacy against surprisingly diverse fungi. Across the phylogenetic spectrum (with the exception of Aspergillus species), yeasts, dermatophytes, dimorphic fungi, and molds were all sensitive to the effects of these polymers. Even fungi intrinsically resistant to current antifungal drugs, such as the causative agents of mucormycosis (Rhizopus spp.) and those with acquired resistance to azole drugs, showed nylon-3 polymer sensitivity. In addition, the emerging pathogens Pseudogymnoascus destructans (cause of white nose syndrome in bats) and Candida auris (cause of nosocomial infections of humans) were also sensitive. The three nylon-3 polymers exhibited relatively low toxicity toward mammalian cells. These findings raise the possibility that nylon-3 polymers could be useful against fungi for which there are only limited and/or no antifungal agents available at present. IMPORTANCE Fungi reside in all ecosystems on earth and impart both positive and negative effects on human, plant, and animal health. Fungal disease is on the rise worldwide, and there is a critical need for more effective and less toxic antifungal agents. Nylon-3 polymers are short, sequence random, poly-β-amino acid materials that can be designed to manifest antimicrobial properties. Here, we describe three nylon-3 polymers with potent activity against the most phylogenetically diverse set of fungi evaluated thus far in a single study. In contrast to traditional peptides, nylon-3 polymers are highly stable to proteolytic degradation and can be produced efficiently in large quantities at low cost. The ability to modify nylon-3 polymer composition easily creates an opportunity to tailor efficacy and toxicity, which makes these materials attractive as potential broad-spectrum antifungal therapeutics. PMID:29794056
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Epidemiology and treatment approaches in management of invasive fungal infections
Kriengkauykiat, Jane; Ito, James I; Dadwal, Sanjeet S
2011-01-01
Over the past 20 years, the number of invasive fungal infections has continued to persist, due primarily to the increased numbers of patients subjected to severe immunosuppression. Despite the development of more active, less toxic antifungal agents and the standard use of antifungal prophylaxis, invasive fungal infections (especially invasive mold infections) continue to be a significant factor in hematopoietic cell and solid organ transplantation outcomes, resulting in high mortality rates. Since the use of fluconazole as standard prophylaxis in the hematopoietic cell transplantation setting, invasive candidiasis has come under control, but no mold-active antifungal agent (except for posaconazole in the setting of acute myelogenous leukemia and myelodysplastic syndrome) has been shown to improve the survival rate over fluconazole. With the advent of new azole and echinocandin agents, we have seen the emergence of more azole-resistant and echinocandin-resistant fungi. The recent increase in zygomycosis seen in the hematopoietic cell transplantation setting may be due to the increased use of voriconazole. This has implications for the empiric approach to pulmonary invasive mold infections when zygomycosis cannot be ruled out. It is imperative that an amphotericin B product, an antifungal that has never developed resistance in over 50 years, be initiated. The clinical presentations of invasive mold infections and invasive candidiasis can be nonspecific and the diagnostic tests insensitive, so a high index of suspicion and immediate initiation of empiric therapy is required. Unfortunately, our currently available serologic tests do not predict infection ahead of disease, and, therefore cannot be used to initiate “preemptive” therapy. Also, the Aspergillus galactomannan test gives a false negative result in patients receiving antimold prophylaxis, ie, virtually all of our patients with hematologic malignancy and hematopoietic cell transplant recipients. We may eventually be able to select patients at highest risk for invasive fungal infections for prophylaxis by genetic testing. However, with our current armamentarium of antifungal agents and widespread use of prophylaxis in high-risk groups (hematologic malignancy, hematopoietic cell transplantation), we continue to see high incidence and mortality rates, and our future hope lies in reversing the immunosuppression or augmenting the immune system of these severely immunocompromised hosts by developing and utilizing immunotherapy, immunoprophylaxis, and vaccines. PMID:21750627
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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
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Target discovery and antifungal intervention via chemical biology approaches
USDA-ARS?s Scientific Manuscript database
Controlling infective fungi, especially pathogens that produce toxic secondary metabolites, is problematic as effective antimycotic agents are very limited. Moreover, the expansion of fungal resistance to commercial drugs is a global human health issue. Conventional antimycotic agents also cause ser...
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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...
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Vinciguerra, Vittorio; Rojas, Florencia; Tedesco, Viviana; Giusiano, Gustavo; Angiolella, Letizia
2018-05-04
The composition of the essential oils (EOs) of O. vulgare L. EO and T. vulgaris EO, were analyzed by GC and GC-MS. Antifungal activities of the EOs and its main component, carvacrol, were evaluated against 27 clinical isolates of Malassezia furfur. Minimum inhibitory concentrations (MICs) were measured according to the broth microdilution protocols by Clinical and Laboratory Standards Institute (CLSI) modified for Malassezia spp. EOs and carvacrol showed low MIC values ranged 450-900 μg/ml against M. furfur. No differences in EOs antifungal activity were observed in sensitive to resistant fluconazole isolates. The antifungal activity obtained showed O. vulgare EO, T. vulgaris EO and carvacrol, their compound, as potential antimicrobial agents against M. furfur, yeast associated with human mycoses.
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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
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Sütçü, Murat; Acar, Manolya; Genç, Gonca Erköse; Kökçü, İlknur; Aktürk, Hacer; Atay, Gürkan; Törun, Selda Hançerli; Salman, Nuran; Erturan, Zayre; Somer, Ayper
2017-01-01
Aim Non-albicans Candida species and resistant microorganisms have been more commonly isolated in invasive candidiasis in recent years. The aim of this study was to evaluate the distrubution of Candida spp and antifungal resistance in our clinic. Material and Methods Fifty-four Candida isolates and antifungal susceptibility results obtained from patients diagnosed as having invasive candidiasis between December 2012 and June 2016 were included. Clinical and laboratory data were retrospectively analyzed. E-test method was used in order to determine antifungal susceptibilities of Candida spp for amphotericin B, fluconazole, voriconazole, ketoconazole, itraconazole, anidulafungin, caspofungin, and flucytosine. Results The clinical diagnoses of the patients were candidemia (n=27, 50%), catheter-related blood stream infection (n=1, 1.8%), urinary tract infection (n=13, 24%), surgical site infection (n=4, 7.4%), intraabdominal infection (n=3, 5.5%), empyema (n=2, 3.7%), and pneumonia (n=4, 7.4%). The most common isolated agent was C. albicans (n=27, 50%) and the others were C. parapsilosis (n=13, 24%), C. tropicalis (n=6, 11.1%), C. glabrata (n=3, 5.6%), C. lusitaniae (n=2, 3.7%), and unspecified Candida spp. (n=3, 5.6%). Fluconazole resistance was 7.4% among all isolates. Resistance against itraconazole, ketoconazole, anidulafungin, voriconazole and caspofungin were 33.3%, 12.5%, 11.1%, 5%, and 2.5%, respectively. Isolates presented intermediate resistance against itraconazole (41.7%), voriconazole (5.6%), and amphotericin B (3.7%) to varying extents. All of the isolates were susceptible to flucytosine. Conclusions In our clinic, C. albicans and non-albicans Candida species were equally distributed and antifungal susceptibilities against major antifungal agents such as fluconazole, amphotericin B, and caspofungin were found considerably high. PMID:29062248
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Pfaller, Michael A; Messer, Shawn A; Jones, Ronald N; Castanheira, Mariana
2015-09-01
The SENTRY Antifungal Surveillance Program monitors global susceptibility rates of newer and established antifungal agents. We report the in vitro activity of seven antifungal agents against 496 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 20 laboratories in the Asia-Western Pacific (APAC) region during 2010 through 2012. Anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole and voriconazole were susceptibility tested using CLSI methods and species-specific interpretive criteria. Sequencing of fks hot spots was performed for echinocandin-resistant strains. Isolates included 13 species of Candida (n=460), 5 species of non-Candida yeasts (21), 5 species of Aspergillus (11) and 4 other molds. Echinocandin resistance was uncommon among eight species of Candida and was only detected in three isolates of Candida glabrata, two from Australia harboring mutations in fks1 (F625S) and fks2 (S663P). Resistance to the azoles was much more common and was observed among all species with the exception of Candida dubliniensis. Fluconazole resistance rates observed with C. glabrata (6.8%) was comparable to that seen with Candida parapsilosis (5.7%) and Candida tropicalis (3.6%). Cross resistance among the triazoles was seen with each of these three species. The mold-active azoles and the echinocandins were all active against isolates of Aspergillus fumigatus. Azole resistance was not detected among the isolates of Cryptococcus neoformans. Antifungal resistance is uncommon among isolates of fungi causing invasive fungal infections in the APAC region. As in other regions of the world, emerging resistance to the echinocandins among invasive isolates of C. glabrata bears close monitoring.
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Is candidiasis the true cause of vulvovaginal irritation in women with diabetes mellitus?
Rowe, B R; Logan, M N; Farrell, I; Barnett, A H
1990-01-01
Vulvovaginitis is common in diabetic women and is often treated with antifungal agents on the assumption that the causative organism is Candida albicans. In a survey of 100 consecutive diabetic women attending a diabetes clinic 36 had complained to their general practitioner about vulvovaginal irritation during the past three years and 26 were treated with antifungal agents without a vaginal examination or swabs being taken. In a separate study 27 post-menopausal women with non-insulin dependent diabetes and symptoms of vulvovaginitis were investigated. The organisms cultured were: Candida albicans (n = 6), beta haemolytic streptococci (n = 14), Gardnerella vaginalis (n = 2), Staphylococcus aureus (n = 2), Streptococcus milleri (n = 1), Streptococcus faecalis (n = 1), Klebsiella oxytoca (n = 1), no organisms (n = 3). Where a bacterial organism was isolated symptoms resolved in all but one case with appropriate antibiotic treatment. It is recommended that the practice of initiating antifungal treatment without taking high vaginal swabs should be reviewed and treatment should be given specifically rather than empirically. PMID:2131794
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Dysregulation of Ion Homeostasis by Antifungal Agents
Zhang, Yongqiang; Muend, Sabina; Rao, Rajini
2012-01-01
Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides. PMID:22493595
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Is candidiasis the true cause of vulvovaginal irritation in women with diabetes mellitus?
Rowe, B R; Logan, M N; Farrell, I; Barnett, A H
1990-08-01
Vulvovaginitis is common in diabetic women and is often treated with antifungal agents on the assumption that the causative organism is Candida albicans. In a survey of 100 consecutive diabetic women attending a diabetes clinic 36 had complained to their general practitioner about vulvovaginal irritation during the past three years and 26 were treated with antifungal agents without a vaginal examination or swabs being taken. In a separate study 27 post-menopausal women with non-insulin dependent diabetes and symptoms of vulvovaginitis were investigated. The organisms cultured were: Candida albicans (n = 6), beta haemolytic streptococci (n = 14), Gardnerella vaginalis (n = 2), Staphylococcus aureus (n = 2), Streptococcus milleri (n = 1), Streptococcus faecalis (n = 1), Klebsiella oxytoca (n = 1), no organisms (n = 3). Where a bacterial organism was isolated symptoms resolved in all but one case with appropriate antibiotic treatment. It is recommended that the practice of initiating antifungal treatment without taking high vaginal swabs should be reviewed and treatment should be given specifically rather than empirically.
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Ozkan, Semiha; Kaynak, Fatma; Kalkanci, Ayse; Abbasoglu, Ufuk; Kustimur, Semra
2005-05-01
Slime and proteinase activity of 54 strains consisting of 19 Candida parapsilosis and 35 C. albicans strains isolated from blood samples were investigated in this study. Ketoconazole, amphothericin B, and fluconazole susceptibility of Candida species were compared with slime production and proteinase activity of these species. For both Candida species, no correlation was detected between the slime activity and minimum inhibitory concentration (MIC) values of the three antifungal agents. For both Candida species no correlation was detected between the proteinase activity and the MIC values of amphothericin B, and fluconazole however, statistically significant difference, was determined between the proteinase activity and MIC values of ketoconazole (p = 0.007). Slime production was determined by using modified Christensen macrotube method and proteinase activity was measured by the method of Staib. Antifungal susceptibility was determined through the guidelines of National Committee for Laboratory Standards (NCCLS M27-A).
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Dysregulation of ion homeostasis by antifungal agents.
Zhang, Yongqiang; Muend, Sabina; Rao, Rajini
2012-01-01
Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca(2+) burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca(2+) stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.
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Simonetti, Giovanna; Tocci, Noemi; Valletta, Alessio; Brasili, Elisa; D'Auria, Felicia Diodata; Idoux, Alicia; Pasqua, Gabriella
2016-01-01
Xanthone-rich extracts from Hypericum perforatum root cultures grown in a Mist Bioreactor as antifungal agents against Malassezia furfur. Extracts of Hypericum perforatum roots grown in a bioreactor showed activity against planktonic cells and biofilm of Malassezia furfur. Dried biomass, obtained from roots grown under controlled conditions in a ROOTec mist bioreactor, has been extracted with solvents of increasing polarity (i.e. chloroform, ethyl acetate and methanol). The methanolic fraction was the richest in xanthones (2.86 ± 0.43 mg g(-1) DW) as revealed by HPLC. The minimal inhibitory concentration of the methanol extract against M. furfur planktonic cells was 16 μg mL(-1). The inhibition percentage of biofilm formation, at a concentration of 16 μg mL(-1), ranged from 14% to 39%. The results show that H. perforatum root extracts could be used as new antifungal agents in the treatment of Malassezia infections.
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Jung, Sook-In; Shin, Jong Hee; Song, Jae-Hoon; Peck, Kyong Ran; Lee, Kyungwon; Kim, Mi-Na; Chang, Hyun Ha; Moon, Chi Sook
2010-06-01
Multicenter data on in vitro susceptibility of Candida bloodstream isolates to echinocandin antifungal agents is still lacking in South Korea. We performed a prospective multicenter study to determine the species distribution of Candida bloodstream isolates and their susceptibility to five antifungal agents, including caspofungin and micafungin. A total of 639 isolates were collected from 20 tertiary hospitals between September 2006 and August 2007. Antifungal susceptibilities were determined through the use of the CLSI broth microdilution method M27-A3. The overall species distribution was as follows; Candida albicans (38%), Candida parapsilosis (26%), Candia tropicalis (20%), Candida glabrata (11%), and miscellaneous Candida species (5%). Although C. parapsilosis and miscellaneous Candida species were less susceptible to both echinocandins, all 639 isolates were susceptible to both caspofungin and micafungin (MIC,
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Yabes, Joseph M.; White, Brian K.; Murray, Clinton K.; Sanchez, Carlos J.; Mende, Katrin; Beckius, Miriam L.; Zera, Wendy C.; Wenke, Joseph C.; Akers, Kevin S.
2016-01-01
Soft-tissue invasive fungal infections are increasingly recognized as significant entities directly contributing to morbidity and mortality. They complicate clinical care, requiring aggressive surgical debridement and systemic antifungal therapy. To evaluate new topical approaches to therapy, we examined the antifungal activity and cytotoxicity of Manuka Honey (MH) and polyhexamethylene biguanide (PHMB). The activities of multiple concentrations of MH (40%, 60%, 80%) and PHMB (0.01%, 0.04%, 0.1%) against 13 clinical mold isolates were evaluated using a time-kill assay between 5 min and 24 h. Concentrations were selected to represent current clinical use. Cell viability was examined in parallel for human epidermal keratinocytes, dermal fibroblasts and osteoblasts, allowing determination of the 50% viability (LD50) concentration. Antifungal activity of both agents correlated more closely with exposure time than concentration. Exophiala and Fusarium growth was completely suppressed at 5 min for all PHMB concentrations, and at 12 and 6 h, respectively, for all MH concentrations. Only Lichtheimia had persistent growth to both agents at 24 h. Viability assays displayed concentration-and time-dependent toxicity for PHMB. For MH, exposure time predicted cytotoxicity only when all cell types were analyzed in aggregate. This study demonstrates that MH and PHMB possess primarily time-dependent antifungal activity, but also exert in vitro toxicity on human cells which may limit clinical use. Further research is needed to determine ideal treatment strategies to optimize antifungal activity against molds while limiting cytotoxicity against host tissues in vivo. PMID:27601610
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In vitro susceptibility of Trichomonas vaginalis to 50 antimicrobial agents.
Sears, S D; O'Hare, J
1988-01-01
We determined the susceptibilities of five strains of Trichomonas vaginalis, one of which was metronidazole resistant, to 50 antimicrobial agents. For the metronidazole-susceptible strains, the most active agents were metronidazole, tinidazole, mebendazole, furazolidone, and anisomycin. Against the resistant strain mebendazole, furazolidone, and anisomycin were the most active. Antifungal agents, beta-lactams, macrolides, aminoglycosides, and folic acid antagonists were ineffective against all strains. PMID:3258142
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Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex.
Reis, M P C; Carvalho, C R C; Andrade, F A; Fernandes, O F L; Arruda, W; Silva, M R R
2016-08-01
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex. Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml(-1) to 21·6% after exposure to 64 μg ml(-1) of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy. Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi. This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis. © 2016 The Society for Applied Microbiology.
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Jafari, Samaneh; Aghaei, Seyed-Soheil; Afifi-Sabet, Hossein; Shams-Ghahfarokhi, Masoomeh; Jahanshiri, Zahra; Gholami-Shabani, Mohammadhassan; Shafiei-Darabi, Seyedahmad; Razzaghi-Abyaneh, Mehdi
2018-01-01
In the present study, halophilic bacteria communities were explored in saline soils of Howze-Soltan playa in Iran with special attention to their biological activity against an aflatoxigenic Aspergillus parasiticus NRRL 2999. Halophilic bacteria were isolated from a total of 20 saline soils using specific culture media and identified by 16S rRNA sequencing in neighbor-joining tree analysis. Antifungal and antiaflatoxigenic activities of the bacteria were screened by a nor-mutant A. parasiticus NRRL 2999 using visual agar plate assay and confirmed by high-performance liquid chromatography. Among a total of 177 halophilic bacteria belonging to 11 genera, 121 isolates (68.3%) inhibited A. parasiticus growth and/or aflatoxin production. The most potent inhibitory bacteria of the genera Bacillus, Paenibacillus and Staphylococcus were distributed in three main phylogenetic clusters as evidenced by 16S rRNA sequence analysis. A. parasiticus growth was inhibited by 0.7-92.7%, while AFB 1 and AFG 1 productions were suppressed by 15.1-98.9 and 57.0-99.6%, respectively. Taken together, halophilic bacteria identified in this study may be considered as potential sources of novel bioactive metabolites as well as promising candidates to develop new biocontrol agents for managing toxigenic fungi growth and subsequent aflatoxin contamination of food and feed in practice.
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Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review.
Viana, Paula Gonçalves; Figueiredo, Anna Barreto Fernandes; Gremião, Isabella Dib Ferreira; de Miranda, Luisa Helena Monteiro; da Silva Antonio, Isabela Maria; Boechat, Jéssica Sepulveda; de Sá Machado, Ana Caroline; de Oliveira, Manoel Marques Evangelista; Pereira, Sandro Antonio
2018-04-01
Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.
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Ogunshe, Adenike A. O.; Adepoju, Adedayo A.; Oladimeji, Modupe E.
2011-01-01
Objective: This study aimed at evaluating the in vitro efficacy and health implications of inconsistencies in different production batches of antimycotic drugs. Materials and Methods: in vitro susceptibility profiles of 36 Candida spp. – C. albicans (19.4%), C. glabrata (30.6%), C. tropicalis (33.3%), and C. pseudotropicalis (16.7%) – obtained from human endocervical and high vaginal swabs (ECS/HVS) to two different batches (B1 and B2) of six antimycotic drugs (clotrimazole, doxycycline, iconazole, itraconazole, metronidazole and nystatin) was determined using modified agar well-diffusion method. Results: None of the Candida strains had entirely the same (100%) susceptibility / resistance profiles in both batches of corresponding antimycotic drugs; while, different multiple antifungal susceptibility (MAS) rates were also recorded in batches 1 and 2 for corresponding antifungals. Only 14.3%, 27.3%, 16.7-33.3%, and 8.3-25.0% of C. albicans, C. glabrata, C. pseudotropicalis, and C. tropicalis strains, respectively, had similar susceptibility/resistance profiles toward coressponding antifungal agents in both batches; while up to 57.1% of C. albicans, 45.5% of C. glabrata, 66.7% of C. pseudotropicalis, and 50.0% of C. tropicalis strains were susceptible to one batch of antifungals but resistant to corresponding antifungals in the second batch. As high as 71.4% (C. albicans), 73.0% (C. glabrata), 50.0% (C. pseudotropicalis), and 66.74% (C. tropicalis) strains had differences of ≥ 10.0 mm among corresponding antimycotic agents. Conclusions: Candida strains exhibited different in vitro susceptibility / resistance patterns toward two batches of corresponding antimycotic agents, which has clinical implications on the efficacy of the drugs and treatment of patients. The findings of the present study will be of benefit in providing additional information in support of submission of drugs for registration to appropriate regulatory agencies. PMID:21430967
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Saravana Kumar, P; Yuvaraj, P; Gabrial Paulraj, M; Ignacimuthu, S; Abdullah Al-Dhabi, N
2018-06-05
The present study was aimed to isolate bioactive actinomycetes with antifungal properties. Twenty-seven distinct soil derived actinomycetes were investigated for their antifungal activities. Among these, one isolate exhibited significant antifungal activity. Phenotypic and 16s rRNA gene sequence analysis strongly suggested that the active isolate BG4 belonged to the genus Streptomyces. Further, the chemical investigation of the active extract resulted in the isolation of a major compound and it was structurally elucidated as phenyl acetic acid (PAA). PAA exhibited promising antifungal activity with 100% inhibition, ranging from 31.25 to 25μg/mL. It is to be noted that PAA is naturally occurring and biologically active auxin. In addition, it has also been hypothesized that phytohormone endorsing the source of soil-symbionts has similar pathways for synthesizing compounds and its congeners of host due to horizontal gene transfer. These findings demonstrate that microbially derived phytohormone can be used to treat fungal infections. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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1988-08-01
include the aminoglycosides, the aminocyclitols (spectinomycin), nalidixic acid, trimethoprim, vancomycin, metronidazole , lincomycin, cephalosporins...and antifungal agents such as nystatin and amphotericin B. This is why gentamicin, streptomycin, vancomycin and antifungals may be used in...often used are gentamicin or streptomycin, vancomycin, and amphotericin B or nystatin . Using 2-SP with antimicrobials will keep over 99% of cell
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Antifungal Activity of Maytenin and Pristimerin
Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa
2012-01-01
Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379
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Arendrup, Maiken C; Cuenca-Estrella, Manuel; Lass-Flörl, Cornelia; Hope, William W
2013-12-01
Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations. Therefore, accurate susceptibility testing and appropriate clinical breakpoints for the interpretation of susceptibility results have become increasingly important. Here we review the underlying methodology by which breakpoints have been selected by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Five parameters are evaluated: dosing regimens used; EUCAST MIC distributions from multiple laboratories, species and compound specific epidemiological cut off values (upper MIC limits of wild type isolates or ECOFFs), pharmacokinetic/pharmacodynamic relationships and targets associated with outcome and finally clinical data by species and MIC when available. The general principles are reviewed followed by a detailed review of the individual aspects for Candida species and the three echinocandins and for Aspergillus and the three mould-active azoles. This review provides an update of the subcommittee on antifungal susceptibility testing (AFST) of the EUCAST methodology and summarises the current EUCAST breakpoints for Candida and Aspergillus. Recommendations about applicability of antifungal susceptibility testing in the routine setting are also included. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Maldonado, Natalia Andrea; Cano, Luz Elena; De Bedout, Catalina; Arbeláez, Carlos Alberto; Roncancio, Gustavo; Tabares, Angela María; Robledo, Carlos Gonzalo; Robledo, Jaime
2014-06-01
Candida is the most important agent of fungal infections. Several risk factors have been described associated with invasive infection by fluconazole-resistant Candida spp. A prospective cross-sectional study with case-control analysis was conducted. Case group patients with fluconazole-resistant Candida isolate were included; control group were patients with fluconazole-susceptible Candida spp. A multivariate logistic regression model was performed. Three hundred isolates of Candida spp. were analyzed. Most frequent species were Candida albicans/Candida dubliniensis (48.3%) and Candida tropicalis (22.3%). Posaconazole susceptibility was 93.7%; voriconazole, 84%; and fluconazole, 78.7%. Susceptibility to anidulafungin and caspofungin was 92.7% and 92.3%, respectively. Neutropenia (adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.0-43.1), antifungal exposure (aOR 5.1, 95% CI 2.3-11.2), and antituberculosis therapy (aOR 7.7, 95% CI 1.4-43.2) were associated to fluconazole resistance. Susceptibility results are useful to guide the selection of empiric antifungal treatment and the design of local therapeutic guidelines. Previous antifungal exposure suggests possible resistance to fluconazole, pointing towards the selection of a different class of antifungal agents. Copyright © 2014 Elsevier Inc. All rights reserved.
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Roles of a solo LuxR in the biological control agent Lysobacter enzymogenes strain OH11.
Qian, Guoliang; Xu, Feifei; Venturi, Vittorio; Du, Liangcheng; Liu, Fengquan
2014-03-01
Lysobacter enzymogenes is a ubiquitous plant-associated and environmentally friendly bacterium emerging as a novel biological control agent of plant disease. This bacterium produces diverse antifungal factors, such as lytic enzymes and a secondary metabolite (heat-stable antifungal factor [HSAF]) having antifungal activity with a novel structure and mode of action. The regulatory mechanisms for biosynthesis of antifungal factors is largely unknown in L. enzymogenes. The solo LuxR proteins have been shown to be widespread, playing important roles in plant-associated bacteria. Here, we cloned and studied a solo LuxR protein, LesR, from L. enzymogenes strain OH11. Overexpression but not deletion of lesR significantly impaired HSAF biosynthesis levels and antimicrobial activities but did not show visible effect on production of major lytic enzymes. Overexpression of lesR also led to remarkably accelerated cell aggregation and induced production of a melanin-like pigment in L. enzymogenes; these two phenotypes are mediated by the diffusible factor cell-to-cell signaling system of L. enzymogenes. The C-terminus helix-turn-helix domain was shown to be critical for several lesR-controlled functions. Overall, our study provides the first example of the roles and mechanisms of a solo LuxR protein in a plant-associated L. enzymogenes.
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Discovery of benzotriazole-azo-phenol/aniline derivatives as antifungal agents.
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.
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Viridepyronone, a new antifungal 6-substituted 2H-pyran-2-one produced by Trichoderma viride.
Evidente, Antonio; Cabras, Annalisa; Maddau, Lucia; Serra, Salvatorica; Andolfi, Anna; Motta, Andrea
2003-11-19
A new antifungal 6-substituted 2H-pyran-2-one, named viridepyronone, has been isolated from a cultural filtrate of a strain of Trichoderma viride showing antagonistic activity in vitro toward Sclerotium rolfsii, which is the causal agent of crown and stem rot of artichoke. Viridepyronone was characterized as 6-(4-oxopentyl)-2H-pyran-2-one 2 with spectroscopic methods. Bioassays showed that viridepyronone had a good antifungal activity against S. rolfsii, and its minimum inhibitory concentration (over 90% inhibition) was found to be 196 microg/mL. This is the first report of viridepyronone produced by any species of fungi.
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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
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Biogenic Silver Nanoparticles by Gelidiella acerosa Extract and their Antifungal Effects
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
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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.
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Álvarez-Pérez, José Manuel; González-García, Sandra; Cobos, Rebeca; Olego, Miguel Ángel; Ibañez, Ana; Díez-Galán, Alba; Garzón-Jimeno, Enrique
2017-01-01
ABSTRACT Endophytic and rhizosphere actinobacteria isolated from the root system of 1-year-old grafted Vitis vinifera plants were evaluated for their activities against fungi that cause grapevine trunk diseases. A total of 58 endophytic and 94 rhizosphere isolates were tested. Based on an in vitro bioassay, 15.5% of the endophytic isolates and 30.8% of the rhizosphere isolates exhibited antifungal activity against the fungal pathogen Diplodia seriata, whereas 13.8% of the endophytic isolates and 16.0% of the rhizosphere isolates showed antifungal activity against Dactylonectria macrodidyma (formerly Ilyonectria macrodidyma). The strains which showed the greatest in vitro efficacy against both pathogens were further analyzed for their ability to inhibit the growth of Phaeomoniella chlamydospora and Phaeoacremonium minimum (formerly Phaeoacremonium aleophilum). Based on their antifungal activity, three rhizosphere isolates and three endophytic isolates were applied on grafts in an open-root field nursery in a 3-year trial. The field trial led to the identification of one endophytic strain, Streptomyces sp. VV/E1, and two rhizosphere isolates, Streptomyces sp. VV/R1 and Streptomyces sp. VV/R4, which significantly reduced the infection rates produced by the fungal pathogens Dactylonectria sp., Ilyonectria sp., P. chlamydospora, and P. minimum, all of which cause young grapevine decline. The VV/R1 and VV/R4 isolates also significantly reduced the mortality level of grafted plants in the nursery. This study shows that certain actinobacteria could represent a promising new tool for controlling fungal trunk pathogens that infect grapevine plants through the root system in nurseries. IMPORTANCE Grapevine trunk diseases are a major threat to the wine and grape industry worldwide. They cause a significant reduction in yields as well as in grape quality, and they can even cause plant death. Trunk diseases are caused by fungal pathogens that enter through pruning wounds and/or the root system. Although different strategies have recently been developed to protect pruning wounds using antifungal compounds (natural or synthetic) or biocontrol agents, no tools are yet available for controlling soil pathogens that infect plants through their root system. This study shows that different actinobacterial isolates, when applied to grafts in a nursery, can significantly reduce the infection rate caused by fungal pathogens that enter through the root system. This is a new, promising, and green alternative for preventing the decline of young grapevines in nurseries and vineyards. PMID:28986378
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Álvarez-Pérez, José Manuel; González-García, Sandra; Cobos, Rebeca; Olego, Miguel Ángel; Ibañez, Ana; Díez-Galán, Alba; Garzón-Jimeno, Enrique; Coque, Juan José R
2017-12-15
Endophytic and rhizosphere actinobacteria isolated from the root system of 1-year-old grafted Vitis vinifera plants were evaluated for their activities against fungi that cause grapevine trunk diseases. A total of 58 endophytic and 94 rhizosphere isolates were tested. Based on an in vitro bioassay, 15.5% of the endophytic isolates and 30.8% of the rhizosphere isolates exhibited antifungal activity against the fungal pathogen Diplodia seriata , whereas 13.8% of the endophytic isolates and 16.0% of the rhizosphere isolates showed antifungal activity against Dactylonectria macrodidyma (formerly Ilyonectria macrodidyma ). The strains which showed the greatest in vitro efficacy against both pathogens were further analyzed for their ability to inhibit the growth of Phaeomoniella chlamydospora and Phaeoacremonium minimum (formerly Phaeoacremonium aleophilum ). Based on their antifungal activity, three rhizosphere isolates and three endophytic isolates were applied on grafts in an open-root field nursery in a 3-year trial. The field trial led to the identification of one endophytic strain, Streptomyces sp. VV/E1, and two rhizosphere isolates, Streptomyces sp. VV/R1 and Streptomyces sp. VV/R4, which significantly reduced the infection rates produced by the fungal pathogens Dactylonectria sp., Ilyonectria sp., P. chlamydospora , and P. minimum , all of which cause young grapevine decline. The VV/R1 and VV/R4 isolates also significantly reduced the mortality level of grafted plants in the nursery. This study shows that certain actinobacteria could represent a promising new tool for controlling fungal trunk pathogens that infect grapevine plants through the root system in nurseries. IMPORTANCE Grapevine trunk diseases are a major threat to the wine and grape industry worldwide. They cause a significant reduction in yields as well as in grape quality, and they can even cause plant death. Trunk diseases are caused by fungal pathogens that enter through pruning wounds and/or the root system. Although different strategies have recently been developed to protect pruning wounds using antifungal compounds (natural or synthetic) or biocontrol agents, no tools are yet available for controlling soil pathogens that infect plants through their root system. This study shows that different actinobacterial isolates, when applied to grafts in a nursery, can significantly reduce the infection rate caused by fungal pathogens that enter through the root system. This is a new, promising, and green alternative for preventing the decline of young grapevines in nurseries and vineyards. Copyright © 2017 American Society for Microbiology.
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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
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Grzesiak, Barbara; Kołodziej, Barbara; Głowacka, Anna; Krukowski, Henryk
2018-06-01
The aim of the study was to evaluate the effect of essential oils obtained from Thymus vulgaris L., Origanum vulgare L., Origanum majerana L., Mentha × piperita L. and Allium ursinum L. against Prototheca zopfii strains that cause inflammation of the udder (mastitis) in cows. The study was conducted on ten strains derived from milk samples. The microdilution method was used to determine the sensitivity of P. zopfii strains to the studied essential oils, and the disk diffusion method was used to determine the sensitivity to antifungal chemotherapeutics. The plates were incubated for 48 h at 37 °C under aerobic conditions. All strains of algae were sensitive to the essential oils marjoram, thyme and oregano and resistant to mint and garlic oils. MIC values ranged from 0.25 to 1 μl/ml. Marjoram oil demonstrated the greatest activity, and oregano oil the weakest. Among the antifungal agents tested, 90% of strains showed sensitivity to nystatin. One of the tested strains (71/IV) was resistant to all investigated antifungal agents. The tested essential oils are known to have anti-algae activity and can be used as natural agents for prophylaxis in animals, particularly in mastitis-affected cows.
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Clinical Appearance of Oral Candida Infection and Therapeutic Strategies
Patil, Shankargouda; Rao, Roopa S.; Majumdar, Barnali; Anil, Sukumaran
2015-01-01
Candida species present both as commensals and opportunistic pathogens of the oral cavity. For decades, it has enthralled the clinicians to investigate its pathogenicity and to improvise newer therapeutic regimens based on the updated molecular research. Candida is readily isolated from the oral cavity, but simple carriage does not predictably result in development of an infection. Whether it remains as a commensal, or transmutes into a pathogen, is usually determined by pre-existing or associated variations in the host immune system. The candida infections may range from non-life threatening superficial mucocutaneous disorders to invasive disseminated disease involving multiple organs. In fact, with the increase in number of AIDS cases, there is a resurgence of less common forms of oral candida infections. The treatment after confirmation of the diagnosis should include recognizing and eliminating the underlying causes such as ill-fitting oral appliances, history of medications (antibiotics, corticosteroids, etc.), immunological and endocrine disorders, nutritional deficiency states and prolonged hospitalization. Treatment with appropriate topical antifungal agents such as amphotericin, nystatin, or miconazole usually resolves the symptoms of superficial infection. Occasionally, administration of systemic antifungal agents may be necessary in immunocompromised patients, the selection of which should be based upon history of recent azole exposure, a history of intolerance to an antifungal agent, the dominant Candida species and current susceptibility data. PMID:26733948
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Prabhala, R.H.; Maxey, V.; Hicks, M.J.
1986-03-01
Effects of ethanol (1%), propanol (1%) and ciclopirox alamine, an anti-fungal agent, (4 ..mu..g/well), on the peripheral blood lymphocyte functions, including response to T- (Concanavalin A, ConA) and B-cell (Lipopolysaccharide, LPS) mitogens, and presence of functional T-lymphocyte subsets were determined in vitro. Purified human lymphocytes were incubated at 37/sup 0/C for 48 hours with or without test compounds in presence or absence of ConA and LPS. All three compounds suppress the response to T- or B-cell mitogens. The percentage of T-lymphocytes with T-helper characteristics in the presence of ethanol and ciclopirox alamine was increased. All three compounds suppressed the percentagemore » of T-lymphocytes with E-resetting characteristics. Alcohols enhanced the number of natural killer cells, whereas, ciclopirox alamine exhibited the reverse action. Although the alcohols and the anti-fungal agent enhanced the T-helper subpopulation, their response to mitogens was suppressed. This may be due to the suppression of T-cell activating lymphokines. Alcohol metabolite such as acetaldehyde also suppress the number of T-cells and their functions at 0.01% so may also be part of the explanation for immunoalteration.« less
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Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.
2015-01-01
Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV+ individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent. PMID:26596951
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Rank, Leslie A; Walsh, Naomi M; Lim, Fang Yun; Gellman, Samuel H; Keller, Nancy P; Hull, Christina M
2018-01-01
Understanding the dimensions of fungal diversity has major implications for the control of diseases in humans, plants, and animals and in the overall health of ecosystems on the planet. One ancient evolutionary strategy organisms use to manage interactions with microbes, including fungi, is to produce host defense peptides (HDPs). HDPs and their synthetic analogs have been subjects of interest as potential therapeutic agents. Due to increases in fungal disease worldwide, there is great interest in developing novel antifungal agents. Here we describe activity of polymeric HDP analogs against fungi from 18 pathogenic genera composed of 41 species and 72 isolates. The synthetic polymers are members of the nylon-3 family (poly-β-amino acid materials). Three different nylon-3 polymers show high efficacy against surprisingly diverse fungi. Across the phylogenetic spectrum (with the exception of Aspergillus species), yeasts, dermatophytes, dimorphic fungi, and molds were all sensitive to the effects of these polymers. Even fungi intrinsically resistant to current antifungal drugs, such as the causative agents of mucormycosis ( Rhizopus spp.) and those with acquired resistance to azole drugs, showed nylon-3 polymer sensitivity. In addition, the emerging pathogens Pseudogymnoascus destructans (cause of white nose syndrome in bats) and Candida auris (cause of nosocomial infections of humans) were also sensitive. The three nylon-3 polymers exhibited relatively low toxicity toward mammalian cells. These findings raise the possibility that nylon-3 polymers could be useful against fungi for which there are only limited and/or no antifungal agents available at present. IMPORTANCE Fungi reside in all ecosystems on earth and impart both positive and negative effects on human, plant, and animal health. Fungal disease is on the rise worldwide, and there is a critical need for more effective and less toxic antifungal agents. Nylon-3 polymers are short, sequence random, poly-β-amino acid materials that can be designed to manifest antimicrobial properties. Here, we describe three nylon-3 polymers with potent activity against the most phylogenetically diverse set of fungi evaluated thus far in a single study. In contrast to traditional peptides, nylon-3 polymers are highly stable to proteolytic degradation and can be produced efficiently in large quantities at low cost. The ability to modify nylon-3 polymer composition easily creates an opportunity to tailor efficacy and toxicity, which makes these materials attractive as potential broad-spectrum antifungal therapeutics. Copyright © 2018 Rank et al.
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Doped Halloysite Nanotubes for Use in the 3D Printing of Medical Devices.
Weisman, Jeffery A; Jammalamadaka, Udayabhanu; Tappa, Karthik; Mills, David K
2017-12-15
Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections.
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Morphological changes of Ganoderma boninense mycelia after challenged by Trichoderma and Bacillus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alexander, Arnnyitte; Chong, Khim-Phin, E-mail: chongkp@ums.edu.my; Dayou, Jedol
Ganoderma boninense is a fungal pathogen that causes Basal Stem Rot (BSR) disease in oil palm. This deadly disease has caused major losses in the oil palm industry and no remedy is reported to date. The more promising control on G. boninense is the use of biological control agents (BCAs). Despite many attempts in using BCAs as a control agent but evidence on the colonization of BCAs and morphological changes of the pathogen is not well documented. We have investigated the effect of antagonist activity on the combination of Trichoderma spp. and Bacillus spp. on the morphology of G. boninense.more » The antagonist activity was evaluated using agar well diffusion assay. BCAs suppressed the mycelia growth of G. boninense up to 70%. Observation under Scanning Electron Microscopy (SEM) shows these BCAs induced stripping of G. boninense hyphal structure by destroying the cellular structure. Highly disrupted, disaggerated, shrivelled and lysis of G. boninense hyphal were also observed. The antifungal activity of Trichoderma spp. and Bacillus spp. observed could be associated with the production of Cell Wall Degrading Enzymes (CWDE)« less
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Morphological changes of Ganoderma boninense mycelia after challenged by Trichoderma and Bacillus
NASA Astrophysics Data System (ADS)
Alexander, Arnnyitte; Dayou, Jedol; Chong, Khim-Phin
2015-07-01
Ganoderma boninense is a fungal pathogen that causes Basal Stem Rot (BSR) disease in oil palm. This deadly disease has caused major losses in the oil palm industry and no remedy is reported to date. The more promising control on G. boninense is the use of biological control agents (BCAs). Despite many attempts in using BCAs as a control agent but evidence on the colonization of BCAs and morphological changes of the pathogen is not well documented. We have investigated the effect of antagonist activity on the combination of Trichoderma spp. and Bacillus spp. on the morphology of G. boninense. The antagonist activity was evaluated using agar well diffusion assay. BCAs suppressed the mycelia growth of G. boninense up to 70%. Observation under Scanning Electron Microscopy (SEM) shows these BCAs induced stripping of G. boninense hyphal structure by destroying the cellular structure. Highly disrupted, disaggerated, shrivelled and lysis of G. boninense hyphal were also observed. The antifungal activity of Trichoderma spp. and Bacillus spp. observed could be associated with the production of Cell Wall Degrading Enzymes (CWDE).
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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
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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.
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Sujith, K V; Rao, Jyothi N; Shetty, Prashanth; Kalluraya, Balakrishna
2009-09-01
A series of 4-[(4-aryl)methylidene]amino-2-(substituted-4-ylmethyl)-5-{1-[4-(2-methylpropyl)phenyl]ethyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) were synthesized from an arylpropionic acid namely, ibuprofen by a three-component Mannich reaction. Aminomethylation of 4-[(4-aryl)methylidene]amino-5-{1-[4-(2-methylpropyl)phenyl] ethyl}-4H-1,2,4-triazole-3-thiol (5) with formaldehyde and a secondary amine furnished this novel series of Mannich bases (6). Both Schiff bases (5) and Mannich bases (6) were well characterized on the basis of IR, NMR, mass spectral data and elemental analysis. They were screened for their anti-inflammatory, analgesic, antibacterial and antifungal activities. Some of the Mannich bases (6) carrying morpholino and N-methylpiperazino residues were found to be promising anti-inflammatory and analgesic agents.
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Antifungal-protein production in maize (Zea mays) suspension cultures.
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.
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Oz, Yasemin; Qoraan, Iman; Oz, Ali; Balta, Ilknur
2017-01-01
Diabetes patients are particularly susceptible to fungal infections because their vascular and immunological systems are compromised. The present study aimed to determine prevalences of tinea pedis and onychomycosis, factors predisposing to their development, and antifungal susceptibilities of causative fungal species against fluconazole, itraconazole, and terbinafine in patients with type 2 diabetes mellitus (DM). Study groups were defined according to hemoglobin A1C rates of ≥6.5% for the diabetes group and ≤5.7% for control subjects. A total of 600 diabetes subjects and 152 control subjects were evaluated. Rates of onychomycosis and tinea pedis in diabetes patients, and associations with age, gender, blood glucose level, duration of diabetes and serum lipid profile were investigated, as were the distribution and antifungal susceptibility of agents isolated. Patients with onychomycosis and/or tinea pedis numbered 85 in the diabetes group and nine in the control group (P = 0.006). The development of onychomycosis or tinea pedis was significantly related to increasing age and male gender. Although the most common agents were dermatophytes, non-dermatophyte fungal isolates were not uncommon. Terbinafine was the most effective drug against dermatophytes but was invalid for non-dermatophyte isolates by in vitro antifungal susceptibility testing. The development of onychomycosis or tinea pedis was significantly related to type 2 DM, increasing age, and male gender. The most common isolate was Trichophyton rubrum. The isolation and identification of the fungus is important to the effective management of tinea pedis and onychomycosis in diabetes patients because non-dermatophyte fungi can cause these infections. © 2016 The International Society of Dermatology.
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Shi, Jun-yan; Xu, Ying-chun; Shi, Yi; Lü, Huo-xiang; Liu, Yong; Zhao, Wang-sheng; Chen, Dong-mei; Xi, Li-yan; Zhou, Xin; Wang, He; Guo, Li-na
2010-10-01
During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software. The MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested. The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.
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Antifungal activity of gold nanoparticles prepared by solvothermal method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahmad, Tokeer, E-mail: tahmad3@jmi.ac.in; Wani, Irshad A.; Lone, Irfan H.
2013-01-15
Graphical abstract: Gold nanoparticles (7 and 15 nm) of very high surface area (329 and 269 m{sup 2}/g) have been successfully synthesized through solvothermal method by using tin chloride and sodium borohydride as reducing agents. As-prepared gold nanoparticles shows very excellent antifungal activity against Candida isolates and activity increases with decrease in the particle size. Display Omitted Highlights: ► Effect of reducing agents on the morphology of gold nanoparticles. ► Highly uniform and monodisperse gold nanoparticles (7 nm). ► Highest surface area of gold nanoparticles (329 m{sup 2/}g). ► Excellent antifungal activity of gold nanoparticles against Candida strains. -- Abstract:more » Gold nanoparticles have been successfully synthesized by solvothermal method using SnCl{sub 2} and NaBH{sub 4} as reducing agents. X-ray diffraction studies show highly crystalline and monophasic nature of the gold nanoparticles with face centred cubic structure. The transmission electron microscopic studies show the formation of nearly spherical gold nanoparticles of average size of 15 nm using SnCl{sub 2}, however, NaBH{sub 4} produced highly uniform, monodispersed and spherical gold nanoparticles of average grain size of 7 nm. A high surface area of 329 m{sup 2}/g for 7 nm and 269 m{sup 2}/g for 15 nm gold nanoparticles was observed. UV–vis studies assert the excitations over the visible region due to transverse and longitudinal surface plasmon modes. The gold nanoparticles exhibit excellent size dependant antifungal activity and greater biocidal action against Candida isolates for 7 nm sized gold nanoparticles restricting the transmembrane H{sup +} efflux of the Candida species than 15 nm sized gold nanoparticles.« less
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Dananjaya, S H S; Udayangani, R M C; Shin, Sang Yeop; Edussuriya, M; Nikapitiya, Chamilani; Lee, Jehee; De Zoysa, Mahanama
2017-08-01
Fusarium oxysporum is an ascomycete facultative fungus which generally affects to plants. However, it is recently known as a serious emerging opportunistic pathogen of human and other animals. F. oxysporum shows broad resistance to commonly used antifungal agents and therefore development of alternative therapeutic agents is required. In this study, we investigated the antifungal efficacy of plant based natural lawsone against pathogenic F. oxysporum. Antifungal susceptibility test determined the concentration dependent growth inhibition of lawsone against F. oxysporum with minimum inhibitory concentration (MIC) at 100μg/mL. Ultra-structural analysis indicates the prominent damage on cell wall of the mycelium after lawsone treatment, and suggests that it could increase the membrane permeability and disintegration of cells leading to cellular death. Propidium iodide (PI) uptake assay results showed the higher level of cell death in lawsone treated F. oxysporum which further confirms the loss of plasma membrane integrity. Also, detection of reactive oxygen species (ROS) using DCFH-DA has clearly indicated that lawsone (100μg/mL) can induce the ROS level in the filaments of F. oxysporum. MTT assay results showed the loss of viability and germination capacity of F. oxysporum spores by lawsone in concentration dependent manner. Moreover, lawsone treatment induced the mRNA expression of two autophagy related genes (ATG1 and ATG8) indicating that lawsone may activate the autophagy related pathways in F. oxysporum due to the oxidative stress generated by ROS. F. oxysporum infected zebrafish has recovered after lawsone therapy as a topical treatment suggesting that lawsone is a potential natural antifusariosis agent. Copyright © 2017 Elsevier GmbH. All rights reserved.
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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.
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Antimicrobial and antifungal activities of the extracts and essential oils of Bidens tripartita.
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.
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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.
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Antifungal Effects of Silver Nanoparticles (AgNPs) against Various Plant Pathogenic Fungi.
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.
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Shilabin, Abbas Gholipour; Kasanah, Noer; Wedge, David E; Hamann, Mark T
2007-09-06
Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.
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Naz, Sehar Afshan; Yaseen, Muhammad; Jabeen, Nusrat; Shafique, Maryam
2017-06-01
To determine the presence of pathogenic fungal strains in areas where pigeons are present in a large number. This study was conducted at the Federal Urdu University of Arts, Science and Technology, Karachi, from February 2015 to March2016, and comprised samples of soil contaminated with pigeons' excreta. The samples were collected from 20 different pigeon-feeding places in the city. These samples were processed for the isolation and identification of fungi by using standard conventional methods. The fungal strains isolated were also tested for their susceptibility to commonly used antifungal agents by disc diffusion technique. There were 105 samples. A wide variety of fungal strains belonging to different genera of Aspergillus, Rhizopus, Penicillium, Fusarium and Candida were isolated and identified by using conventional methods. The antifungal resistance pattern of these strains also depicts emergence of resistance against commonly used antifungal agents such as amphotericin B and fluconazole. The soil and air of places densely populated with pigeons were found to be loaded with fungal spores and many of them were potential pathogens.
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Ioannou, Petros; Andrianaki, Aggeliki; Akoumianaki, Tonia; Kyrmizi, Irene; Albert, Nathaniel; Perlin, David; Samonis, George
2015-01-01
The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae. PMID:26643329
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Singh, Shweta; Fatima, Zeeshan; Hameed, Saif
2016-07-01
The anticandidal potential of Geraniol (Ger) against Candida albicans has already been established. The present study reveals deeper insights into the mechanisms of action of Ger. We observed that the repertoire of antifungal activity was not only limited to C. albicans and its clinical isolates but also against non-albicans species of Candida. The membrane tampering effect was visualized through transmission electron micrographs, depleted ergosterol levels and altered plasma membrane ATPase activity. Ger also affects cell wall as revealed by spot assays with cell wall-perturbing agents and scanning electron micrographs. Functional calcineurin pathway seems to be indispensable for the antifungal effect of Ger as calcineurin signaling mutant was hypersensitive to Ger while calcineurin overexpressing strain remained resistant. Ger also causes mitochondrial dysfunction, impaired iron homeostasis and genotoxicity. Furthermore, Ger inhibits both virulence attributes of hyphal morphogenesis and biofilm formation. Taken together, our results suggest that Ger is potential antifungal agent that warrants further investigation in clinical applications so that it could be competently employed in therapeutic strategies to treat Candida infections.
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Yadav, Prem P; Gupta, Prasoon; Chaturvedi, A K; Shukla, P K; Maurya, Rakesh
2005-03-01
Synthesis of nitrogen and sulfur heterocyclic mimics of furanoflavonoids have been achieved for the first time. Synthesized flavonoid alkaloids and thiophenyl flavonoids have been screened for antifungal and antibacterial activities. All the test compounds barring 25 exhibited antifungal activity. The compound 19 was the best and showed comparable MICs to the known compound karanjin. Compounds 5, 12, 14 and 22 also showed comparable MIC to karanjin.
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Athlete's Foot: Clinical Update.
Ramsey, M L
1989-10-01
In brief: Athletes are particularly prone to athlete's foot because they are generally more exposed than others to conditions that encourage fungal growth, eg, communal showers and locker rooms. Diagnosis of athlete's foot rests on clinical suspicion and laboratory testing. Treatment may consist of topical antifungal agents and, for more resistant cases, oral griseofulvin. Preventive measures include keeping the feet dry, wearing nonocclusive leather shoes or sandals and absorbent cotton socks, and applying talcum or antifungal powder at least twice daily.
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Plant-derived antifungal agent poacic acid targets β-1,3-glucan
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
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Selective BET bromodomain inhibition as an antifungal therapeutic strategy
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
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Anti-Aspergillus activity of green coffee 5-O-caffeoyl quinic acid and its alkyl esters.
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.
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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.
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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.
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Geber, A; Hitchcock, C A; Swartz, J E; Pullen, F S; Marsden, K E; Kwon-Chung, K J; Bennett, J E
1995-01-01
We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae. PMID:8593007
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Antifungal activity of low molecular weight chitosan against clinical isolates of Candida spp.
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.
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In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.
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.
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Meena, Khem Raj; Kanwar, Shamsher S.
2015-01-01
A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of the Bacillus genus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families of Bacillus lipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activities, while Surfactin has broad range of potent antibacterial activities and this has also been used as larvicidal agent. Interestingly, lipopeptides being the molecules of biological origin are environmentally acceptable. PMID:25632392
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Khan, J K; Montaseri, H; Poglod, M; Bu, H Z; Daneshtalab, M; Micetich, R G
2000-08-01
A simple and rugged reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection at 263 nm was developed and validated for the analysis of novel triazole antifungal agents SYN-2869 and its derivatives in tissues. The method involved homogenization with 0.01 M phosphate buffer (pH 7.8) for lung, brain and spleen tissues. The liver and kidneys were homogenized with acetonitrile:acetone (1:1). The plasma proteins were precipitated with ice-cold acetonitrile and supernatent was evaporated to dryness. The reconstituted samples were injected onto an HPLC system. SYN-2869 was separated from the matrix components on a symmetry C(18) column using a aqueous mobile phase of acetonitrile and water with a flow rate of 1 mL/min. A step gradient of 40-80% acetonitrile eluted SYN-2869 and the internal standard (SYN-2506). The linear range was 0.5-10 microgram/g (r(2) > 0.99). The limit of quantitation was 0.5 microgram/g. The inter-day precision and accuracy for SYN 2869 standard concentration were from 2.6 to 7.4% and from -1.56 to +3.29%, respectively. The method was applied to tissue samples collected from single intravenous administration to mice to evaluate the distribution of these novel antifungal agents to different tissues. Copyright 2000 John Wiley & Sons, Ltd.
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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
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Lactobacillus amylovorus DSM 19280 as a novel food-grade antifungal agent for bakery products.
Ryan, Liam A M; Zannini, Emanuele; Dal Bello, Fabio; Pawlowska, Agata; Koehler, Peter; Arendt, Elke K
2011-04-29
Mould spoilage is the main cause of substantial economic loss in bakery industry and might also cause public health problems due to the production of mycotoxins. The reduction of mould growth in bakery products is thus of crucial importance and there is great interest to develop safe and efficient strategies for this purpose. In this study Lactobacillus amylovorus DSM19280 has been shown to produce a wide spectrum of antifungal compounds active against common bread spoilage fungi. Among the indicator moulds, Aspergillus fumigatus and Fusarium culmorum were the most sensitive organisms. Several antifungal compounds were found to be present in synthetic medium inoculated with L. amylovorus DSM19280 strain, some of them being reported here for the first time. Wheat doughs fermented with L. amylovorus DSM19280 had good rheological properties and the breads thereof were of high quality as shown by rheofermentometer and texture analyser measurements. The results were compared with those obtained with a control non-antifungal L. amylovorus DSM20531(T) strain, a non-acidified and a chemically acidified dough. The quality of sourdough and bread fermented with L. amylovorus DSM 19280 was comparable to that obtained by using L. amylovorus DSM20531 (T). Additionally, breads were evaluated for the ability to retard the growth of Fusarium culmorum FST 4.05, Aspergillus niger FST4.21, Penicillium expansum FST 4.22, Penicillium roqueforti FST 4.11 and fungal flora from the bakery environment. The biological preservation of bread with L. amylovorus DSM 19280 was also compared to the most commonly used antifungal agent Calcium propionate. Breads containing sourdough fermented with L. amylovorus DSM 19280 were more effective in extending the shelf life of bread than the calcium propionate. Copyright © 2011 Elsevier B.V. All rights reserved.
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Kachuei, R; Khodavaisy, S; Rezaie, S; Sharifynia, S
2016-03-01
Among filamentous fungal pathogens, Aspergillus spp. and zygomycetes account for highest rates of morbidity and mortality among immunocompromised patients. Recently developed antifungal drugs offer the potential to improve management and therapeutic outcomes of fungal infections. The aim of this study was to analyse the in vitro activities of voriconazole, itraconazole, amphotericin B and caspofungin against clinical isolates of Aspergillus spp. and Rhizopus oryzae. The in vitro antifungal susceptibility of 54 isolates belonging to different clinical isolates of Aspergillus spp. and R. oryzae was tested for four antifungal agents using a microdilution reference method (CLSI, M38-A2). All isolates were identified by typical colony and microscopic characteristics, and also characterized by molecular methods. Caspofungin (MEC range: 0.008-0.25 and MEC50: 0.0023μg/mL) was the most active drug in vitro against Aspergillus spp., followed by voriconazole (MIC range: 0.031-8 and MIC50: 0.5μg/mL), itraconazole (MIC range: 0.031-16 and MIC50: 0.25μg/mL), and amphotericin B (MIC range: 0.125-4 and MIC50: 0.5μg/mL), in order of decreasing activity. The caspofungin, voriconazole, and itraconazole demonstrated poor in vitro activity against R. oryzae isolates evaluated, followed by amphotericin B. This study demonstrates that caspofungin had good antifungal activity and azole agents had better activity than amphotericin B against Aspergillus species. Although, azole drugs are considered ineffective against R. oryzae. This result is just from a small scale in vitro susceptibility study and we did not take other factors into consideration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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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.
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Ko, Bor-Sheng; Chen, Wei-Ting; Kung, Hsiang-Chi; Wu, Un-In; Tang, Jih-Luh; Yao, Ming; Chen, Yee-Chun; Tien, Hwei-Fang; Chang, Shan-Chwen; Chuang, Yin-Ching; Lin, Dong-Tsamn
2017-07-25
The Infectious Diseases Society of Taiwan (IDST), the Hematology Society of Taiwan, the Taiwan Society of Blood and Marrow Transplantation, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines cooperatively published this guideline for the use of antifungal agents in hematological patients with invasive fungal diseases (IFDs) in Taiwan. The guideline is the first one endorsed by IDST focusing on selection of antifungal strategies, including prophylaxis, empirical (or symptom-driven) and pre-emptive (or diagnostic-driven) strategy. We suggest a risk-adapted dynamic strategy and provide an algorithm to facilitate decision making in population level as well as for individual patient. Risk assessment and management accordingly is explicitly emphasized. In addition, we highlight the importance of diagnosis in each antifungal strategy among five elements of the antimicrobial stewardship (diagnosis, drug, dose, de-escalation and duration). The rationale, purpose, and key recommendations for the choice of antifungal strategy are summarized, with concise review of international guidelines or recommendation, key original articles and local epidemiology reports. We point out the interaction and influence between elements of recommendations and limitation of and gap between evidences and daily practice. The guideline balances the quality of evidence and feasibility of recommendation in clinical practice. Finally, this version introduces the concept of health economics and provides data translated from local disease burdens. All these contents hopefully facilitate transparency and accountability in medical decision-making, improvements in clinical care and health outcomes, and appropriateness of medical resource allocation. Copyright © 2017. Published by Elsevier B.V.
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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
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Alvarez-Lerma, Francisco; Nolla, Joan; Palomar, Mercedes; León, María A
2003-02-01
Two consensus conferences taking place in the United States and Spain were organized to optimize diagnosis and treatment of Candida spp. infections. Among other results, clinical scenarios in which early prescription of antifungal agents is indicated were identified. To determine the criteria followed by physicians for prescribing antifungal agents in critically ill patients in our country and to investigate adherence to the guidelines proposed by the consensus conferences. A questionnaire was designed and directed to 4th- and 5th-year residents in intensive care medicine and to specialists in intensive care with training in infectious diseases or other medical areas. Four case reports for which expert consensus indicates early antifungal treatment were included in the questionnaire; 1) recurrent peritonitis secondary to perforation of the digestive tract, with mixed flora including fungi; 2) persistent febrile syndrome in a patient with multiple mucosal fungal colonizations treated with broad-spectrum antibiotics; 3) candiduria and pyuria in a febrile patient; and 4) candidemia. A total of 135 questionnaires from 45 different ICUs were returned (60% response rate). In the candidemia and fungal peritonitis examples, early treatment with antifungal agents was indicated in 100% and 85.9% of responses, respectively, whereas for sepsis with multifocal candidiasis and candiduria associated with pyuria and fever, early treatment was prescribed in only 41.5% and 55.6% of responses, respectively. There were no significant differences in response with regard to degree of training of the physicians surveyed. Fluconazole prescription predominated, mainly at doses of 400 mg/day, in mixed peritonitis, disseminated candidiasis and candiduria, whereas amphotericin B lipid formulations were preferentially indicated in cases of candidemia. Antifungal treatment (early or late) was prescribed in all responses for candidemia, in 95.5% for mixed peritonitis (fungi and bacteria), in 79.5% for multifocal candidiasis in patients with persistent sepsis, and in 77.9% for candiduria with fever and pyuria. Adherence to recommendations from the consensus conferences was high among intensive medicine specialists, with no differences according to level of training in infectious diseases.
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Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of Candida glabrata▿
Miyazaki, Taiga; Yamauchi, Shunsuke; Inamine, Tatsuo; Nagayoshi, Yosuke; Saijo, Tomomi; Izumikawa, Koichi; Seki, Masafumi; Kakeya, Hiroshi; Yamamoto, Yoshihiro; Yanagihara, Katsunori; Miyazaki, Yoshitsugu; Kohno, Shigeru
2010-01-01
A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress. PMID:20100876
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Anti-fungal activity of crude extracts and essential oil of Moringa oleifera Lam.
Chuang, Ping-Hsien; Lee, Chi-Wei; Chou, Jia-Ying; Murugan, M; Shieh, Bor-Jinn; Chen, Hueih-Min
2007-01-01
Investigations were carried out to evaluate the therapeutic properties of the seeds and leaves of Moringa oleifera Lam as herbal medicines. Ethanol extracts showed anti-fungal activities in vitro against dermatophytes such as Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis. GC-MS analysis of the chemical composition of the essential oil from leaves showed a total of 44 compounds. Isolated extracts could be of use for the future development of anti-skin disease agents.
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Jahn, B; Stüben, A; Bhakdi, S
1996-01-01
Two colorimetric methods that use Alamar Blue or 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for assaying the in vitro activities of antifungal agents have been described. We report that both tests performed similarly when the antifungal activity of amphotericin B against Candida albicans was determined. However, only the MTT test generated interpretable data when Aspergillus fumigatus was used. PMID:8818910
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de Souza Fernandes, Lígia; Amorim, Yuri Martins; Silva, Elton Libério da; Silva, Samuel Calixto; Santos, Alécia Junia Aparecida; Peixoto, Franciele Natália; Pires, Luara Moniele Neves; Sakamoto, Raquel Yumi; Pinto, Flávia do Carmo Horta; Scarpa, Maria Virgínia Costa; Gonzaga de Freitas Araújo, Marcelo
2018-03-08
Owing to the growing resistance among isolates of Candida species to usual antifungal agents and the well-known therapeutic potential of curcumin, the purpose of this study was to develop and validate a vaginal formulation containing this substance and to evaluating its effectiveness in the treatment of experimental vulvovaginal candidiasis METHODS: Curcumin was incorporated in a vaginal cream in three concentrations (0.01, 0.1 and 1.0%). The different concentrations of the cream and its controls were intravaginally administered in an immunosuppressed rat model to evaluate the efficacy in the treatment of experimental vulvovaginal candidiasis. Samples of the cream were also subjected to centrifugation and physical stability tests and an analytical method for quantification of curcumin was validated based on HPLC RESULTS: The formulation was stable and the HPLC method could be considered suitable for the quantitative determination of curcumin in the cream. After six days of pre-clinical study, the number of infected animals was 1/6 in all groups treated with curcumin vaginal cream and the fungal burden showed a progressive reduction. Reduction of the inflammatory infiltrate was observed in the group treated with 1.0% cream CONCLUSION: Vaginal cream containing curcumin could be considered a promising effective antifungal medicine in the treatment of vulvovaginal candidiasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Amin, Purnima
2014-01-01
Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72) and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72) and Cmax higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension. PMID:25143935
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Zhu, D H; Zhu, X D; Xu, Y Q
2001-11-01
A reversed-phase HPLC method for the determination of phenazine-1-carboxylic acid (PCA) in antifungal agent M18 is established. The mobile phase was a mixture of MeOH-5 mmol/L phosphate buffer (pH 5.0) (60:40, volume ratio). The flow rate was 1.0 mL/min, and the detection wavelength was 248 nm. The linear range and detectable limit were 50 mg/L-500 mg/L and 30 mg/L respectively. The recovery was 97.53% and RSD was 1.5%. The method of PCA extraction and detection has proven to be much faster, simpler, more sensitive, accurate and reproducible than those reported already. The assay results can be used as a very important criterion for large-scale production.
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Narasimhan, Srinivasan; Maheshwaran, Shanmugam; Abu-Yousef, Imad A; Majdalawieh, Amin F; Rethavathi, Janarthanam; Das, Prince Edwin; Poltronieri, Palmiro
2017-02-12
The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.
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Jeon, B J; Kim, J D; Han, J W; Kim, B S
2016-05-01
The objective of this study was to explore antifungal metabolites targeting fungal cell envelope and to evaluate the control efficacy against anthracnose development in pepper plants. A natural product library comprising 3000 microbial culture extracts was screened via an adenylate kinase (AK)-based cell lysis assay to detect antifungal metabolites targeting the cell envelope of plant-pathogenic fungi. The culture extract of Streptomyces mauvecolor strain BU16 displayed potent AK-releasing activity. Rimocidin and a new rimocidin derivative, BU16, were identified from the extract as active constituents. BU16 is a tetraene macrolide containing a six-membered hemiketal ring with an ethyl group side chain instead of the propyl group in rimocidin. Rimocidin and BU16 showed broad-spectrum antifungal activity against various plant-pathogenic fungi and demonstrated potent control efficacy against anthracnose development in pepper plants. Antifungal metabolites produced by S. mauvecolor strain BU16 were identified to be rimocidin and BU16. The compounds displayed potent control efficacy against pepper anthracnose. Rimocidin and BU16 would be active ingredients of disease control agents disrupting cell envelope of plant-pathogenic fungi. The structure and antifungal activity of rimocidin derivative BU16 is first described in this study. © 2016 The Society for Applied Microbiology.
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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
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Farmakiotis, D; Kontoyiannis, D P
2015-05-01
Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de-escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug-drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs. © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
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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.
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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.
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Cavaleiro, C; Pinto, E; Gonçalves, M J; Salgueiro, L
2006-06-01
The increasing resistance to antifungal compounds and the reduced number of available drugs led us to search therapeutic alternatives among aromatic plants and their essential oils, empirically used by antifungal proprieties. In this work the authors report on the antifungal activity of Juniperus essential oils (Juniperus communis ssp. alpina, J. oxycedrus ssp. oxycedrus and J. turbinata). Antifungal activity was evaluated by determination of MIC and MLC values, using a macrodilution method (NCCLS protocols), on clinical and type strains of Candida, Aspergillus and dermatophytes. The composition of the oils was ascertained by GC and GC/MS analysis. All essential oils inhibited test dermatophyte strains. The oil from leaves of J. oxycedrus ssp. oxycedrus is the most active, with MIC and MLC values ranging from 0.08-0.16 microl ml(-1) to 0.08-0.32 microl ml(-1), respectively. This oil is mainly composed of alpha-pinene (65.5%) and delta-3-carene (5.7%). J. oxycedrus ssp. oxycedrus leaf oil proved to be an emergent alternative as antifungal agent against dermatophyte strains. delta-3-Carene, was shown to be a fundamental compound for this activity. Results support that essential oils or some of their constituents may be useful in the clinical management of fungal infections, justifying future clinical trials to validate their use as therapeutic alternatives for dermatophytosis.
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Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.
Arendrup, Maiken Cavling; Patterson, Thomas F
2017-08-15
Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Biancalana, Fernanda Simas Corrêa; Lyra, Luzia; Moretti, Maria Luiza; Schreiber, Angélica Zaninelli
2011-12-01
Studies have demonstrated excellent in vivo efficacy of terbinafine combined with other antifungal agents against dematiaceous molds; however, there is a lack of in vitro studies. Most studies evaluated conidia inocula, but susceptibility testing of hyphae could mimic the fungal status in infected tissues and might reflect the therapeutic potential of the agent. We investigated the in vitro susceptibility of terbinafine alone and in combination with amphotericin B, itraconazole, or voriconazole against conidia by microdilution and dynamic measurement of hyphae growth of dematiaceous molds. The MIC values for hyphae were, until 3 dilutions, below the MIC obtained for conidia. The results indicated 100% synergistic interactions between terbinafine and azoles or amphotericin B in all tests, but lower MICs for hyphae. In conclusion, our findings allow us to say that the hyphal form of tested dematiaceous molds showed high susceptibility to all antifungal agents evaluated, alone and in combination with terbinafine. Copyright © 2011 Elsevier Inc. All rights reserved.
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Ferreira, Soraya M Z M D; Carneiro, Hellem C; Alves, Rosemeire B; Batista, Ana Carolina S; da Silva Junior, Eufranio N; Dias, Gleiston G; Resende, Jarbas M; Santos, Daniel A; Oliveira, Debora L; Rodrigues, Marcio L; Freitas, Rossimiriam P
2018-01-01
Cryptococcosis is a fungal disease of global significance for which new effective treatments are needed. The conjugation of the synthetic antimicrobial peptide fragment UBI 31-38 to a coumarin derivative showed to be an effective approach for the design of a novel anticryptococcal agent. In addition to antifungal activity, the conjugate exhibited intense fluorescence, which could be valuable for mechanistic investigations of this molecule. In this work, we studied the photophysical properties of the conjugate and confocal scanning laser microscopy was used to inspect the distribution of the peptide-coumarin conjugate in Cryptococcus cell. The synergism of this compound with amphotericin B or fluconazole against C. gattii and C. neoformans strains was also investigated. The results indicated that the fluorescent conjugate alone as well as its combination with amphotericin B are promising tools against cryptococcosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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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.
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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
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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.
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Zheng, Bi-Yuan; Ke, Mei-Rong; Lan, Wen-Liang; Hou, Lu; Guo, Jun; Wan, Dong-Hua; Cheong, Ling-Zhi; Huang, Jian-Dong
2016-05-23
A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra-substituted with morpholinyl moieties and their quaternized derivatives have been synthesized and evaluated for their antifungal photodynamic activities toward Candida albicans. The α-substituted, quaternized, and mono-substituted ZnPcs are found to have higher antifungal photoactivity than β-substituted, neutral, and tetra-substituted counterparts. The cationic α-mono-substituted ZnPc (6a) exhibits the highest photocytotoxicity. Moreover, it is more potent than axially di-substituted analogue. The different photocytotoxicities of these compounds have also been rationalized by investigating their spectroscopic and photochemical properties, aggregation trend, partition coefficients, and cellular uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 μM with a light dose of 27 J cm(-2), meaning that 6a is a promising candidate as the antifungal photosensitizer for future investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Souza, Beatriz C C; De Oliveira, Tiago B; Aquino, Thiago M; de Lima, Maria C A; Pitta, Ivan R; Galdino, Suely L; Lima, Edeltrudes O; Gonçalves-Silva, Teresinha; Militão, Gardênia C G; Scotti, Luciana; Scotti, Marcus T; Mendonça, Francisco J B
2012-06-01
A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcus neoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). For antiproliferative activity, the partial least squares (PLS) methodology was applied. Some of the prepared compounds exhibited promising antifungal and proliferative properties. The most active compounds for antifungal activity were cyclohexyl[b]thiophene derivatives, and for antiproliferative activity cycloheptyl[b]thiophene derivatives, especially 2-[(1H-indol-2-yl-methylidene)amino]- 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbonitrile (2r), which inhibited more than 97 % growth of the three cell lines. The PLS discriminant analysis (PLS-DA) applied generated good exploratory and predictive results and showed that the descriptors having shape characteristics were strongly correlated with the biological data.
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Ilk, Sedef; Saglam, Necdet; Özgen, Mustafa
2017-08-01
Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.
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Sensitivity of Candida albicans to essential oils: are they an alternative to antifungal agents?
Bona, E; Cantamessa, S; Pavan, M; Novello, G; Massa, N; Rocchetti, A; Berta, G; Gamalero, E
2016-12-01
Candida albicans is an important opportunistic pathogen, responsible for the majority of yeast infections in humans. Essential oils, extracted from aromatic plants, are well-known antimicrobial agents, characterized by a broad spectrum of activities, including antifungal properties. The aim of this work was to assess the sensitivity of 30 different vaginal isolated strains of C. albicans to 12 essential oils, compared to the three main used drugs (clotrimazole, fluconazole and itraconazole). Thirty strains of C. albicans were isolated from vaginal swab on CHROMagar ™ Candida. The agar disc diffusion method was employed to determine the sensitivity to the essential oils. The antifungal activity of the essential oils and antifungal drugs (clotrimazole, itraconazole and fluconazole) were investigated using a microdilution method. Transmission and scanning electron microscopy analyses were performed to get a deep inside on cellular damages. Mint, basil, lavender, tea tree oil, winter savory and oregano essential oils inhibited both the growth and the activity of C. albicans more efficiently than clotrimazole. Damages induced by essential oils at the cellular level were stronger than those caused by clotrimazole. Candida albicans is more sensitive to different essential oils compared to the main used drugs. Moreover, the essential oil affected mainly the cell wall and the membranes of the yeast. The results of this work support the research for new alternatives or complementary therapies against vaginal candidiasis. © 2016 The Society for Applied Microbiology.
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Effects of beta-thujaplicin on anti-Malassezia pachydermatis remedy for canine otitis externa.
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.
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Plant-derived antifungal agent poacic acid targets β-1,3-glucan
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
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Genetic diversity and antifungal susceptibility of Fusarium isolates in onychomycosis.
Rosa, Priscila D; Heidrich, Daiane; Corrêa, Carolina; Scroferneker, Maria Lúcia; Vettorato, Gerson; Fuentefria, Alexandre M; Goldani, Luciano Z
2017-09-01
Fusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 μg/mL), followed by voriconazole (34.2%, MIC ≤4 μg/mL). In general, Fusarium species presented MIC values >64 μg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis. © 2017 Blackwell Verlag GmbH.
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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.
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Karki, Hari S.; Shrestha, Bishnu K.; Han, Jae Woo; Groth, Donald E.; Barphagha, Inderjit K.; Rush, Milton C.; Melanson, Rebecca A.; Kim, Beom Seok; Ham, Jong Hyun
2012-01-01
Burkholderia glumae is the primary causal agent of bacterial panicle blight of rice. In this study, 11 naturally avirulent and nine virulent strains of B. glumae native to the southern United States were characterized in terms of virulence in rice and onion, toxofalvin production, antifungal activity, pigmentation and genomic structure. Virulence of B. glumae strains on rice panicles was highly correlated to virulence on onion bulb scales, suggesting that onion bulb can be a convenient alternative host system to efficiently determine the virulence of B. glumae strains. Production of toxoflavin, the phytotoxin that functions as a major virulence factor, was closely associated with the virulence phenotypes of B. glumae strains in rice. Some strains of B. glumae showed various levels of antifungal activity against Rhizoctonia solani, the causal agent of sheath blight, and pigmentation phenotypes on casamino acid-peptone-glucose (CPG) agar plates regardless of their virulence traits. Purple and yellow-green pigments were partially purified from a pigmenting strain of B. glumae, 411gr-6, and the purple pigment fraction showed a strong antifungal activity against Collectotrichum orbiculare. Genetic variations were detected among the B. glumae strains from DNA fingerprinting analyses by repetitive element sequence-based PCR (rep-PCR) for BOX-A1R-based repetitive extragenic palindromic (BOX) or enterobacterial repetitive intergenic consensus (ERIC) sequences of bacteria; and close genetic relatedness among virulent but pigment-deficient strains were revealed by clustering analyses of DNA fingerprints from BOX-and ERIC-PCR. PMID:23028972
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Ioannou, Petros; Andrianaki, Aggeliki; Akoumianaki, Tonia; Kyrmizi, Irene; Albert, Nathaniel; Perlin, David; Samonis, George; Kontoyiannis, Dimitrios P; Chamilos, Georgios
2015-12-07
The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Furustrand Tafin, Ulrika; Meis, Jacques F; Trampuz, Andrej
2012-08-01
We evaluated isothermal microcalorimetry for real-time susceptibility testing of non-Aspergillus molds. MIC and minimal effective concentration (MEC) values of Mucorales (n = 4), Fusarium spp. (n = 4), and Scedosporium spp. (n = 4) were determined by microbroth dilution according to the Clinical Laboratory Standard Institute M38-A2 guidelines. Heat production of molds was measured at 37 °C in Sabouraud dextrose broth inoculated with 2.5 × 10(4) spores/mL in the presence of amphotericin B, voriconazole, posaconazole, caspofungin, and anidulafungin. As determined by microcalorimetry, amphotericin B was the most active agent against Mucorales (MHIC 0.06-0.125 μg/mL) and Fusarium spp. (MHIC 1-4 μg/mL), whereas voriconazole was the most active agent against Scedosporium spp. (MHIC 0.25 to 8 μg/mL). The percentage of agreement (within one 2-fold dilution) between the MHIC and MIC (or MEC) was 67%, 92%, 75%, and 83% for amphotericin B, voriconazole, posaconazole, and caspofungin, respectively. Microcalorimetry provides additional information on timing of antifungal activity, enabling further investigation of drug-mold and drug-drug interaction, and optimization of antifungal treatment. Copyright © 2012 Elsevier Inc. All rights reserved.
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Antifungal activity of Brazilian medicinal plants involved in popular treatment of mycoses.
Cruz, M C S; Santos, P O; Barbosa, A M; de Mélo, D L F M; Alviano, C S; Antoniolli, A R; Alviano, D S; Trindade, R C
2007-05-04
A survey of medicinal plants used to treat common mycoses was done in the Curituba district, Sergipe State, Brazil. One hundred inhabitants were interviewed by health agents and traditional healers. Four different plants were the most cited (more than 50% of the citations): Ziziphus joazeiro, Caesalpinia pyramidalis, Bumelia sartorum and Hymenea courbaril. The aqueous extracts obtained following traditional methods and using different parts of these plants, were submitted to drop agar diffusion tests for primary antimicrobial screening. Only the water infusion extract of Ziziphus joazeiro and Caesalpinea pyramidalis presented a significant antifungal activity against Trichophyton rubrum, Candida guilliermondii, Candida albicans, Cryptococcus neoformans and Fonsecaea pedrosoi, when compared to the antifungal agent amphotericin B. The minimal inhibitory concentration (MIC) of the bioactive extracts was evaluated by the microdilution method. Best activity with a MIC of 6.5 microg/ml for both extracts was observed against Trichophyton rubrum and Candida guilliermondii. Ziziphus joazeiro and Caesalpinea pyramidalis extracts presented also low acute toxicity in murine models. The present study validates the folk use of these plant extracts and indicates that they can be effective potential candidates for the development of new strategies to treat fungal infections.
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Effects of lactoferricin B against keratitis-associated fungal biofilms.
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.
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In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia.
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.
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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.
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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
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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.
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Cafarchia, Claudia; Figueredo, Luciana A; Iatta, Roberta; Montagna, Maria Teresa; Otranto, Domenico
2012-03-23
Canine Malassezia dermatitis is frequently treated with systemic ketoconazole (KTZ) and itraconazole (ITZ). However, no information is available on the antifungal susceptibility to azoles and allilamine of Malassezia pachydermatis isolates from dogs with or without skin lesions. The present study was designed to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains from dogs with or without skin lesions to KTZ, ITZ, miconazole (MICO), fluconazole (FLZ), posaconazole (POS), voriconazole (VOR) and terbinafine (TER) using the Clinical and Laboratory Standards Institute reference Broth Microdilution Method (CLSI M27-A2). The association between the susceptibility to antifungal compounds and the origin of M. pachydermatis, from skin with or without lesions has been also assessed. A total of 62 M. pachydermatis strains from healthy dogs (i.e., Group A=30) or with skin lesions (i.e., Group B=32) were tested. ITZ, KTZ and POS showed the highest activity against M. pachydermatis strains, whereas MICO TER and FLZ the lowest. A higher number of Malassezia resistant strains were registered among isolates from Group B than those from Group A. This study indicates that M. pachydermatis strains were susceptible to ITZ, KTZ, and POS. However, dogs with lesions may harbour strains with low susceptibility to antifungal agents and displaying cross-resistance phenomena to azole. The antifungal therapy in Malassezia infections requires careful appraisal of choice of drugs especially in cases of unresponsiveness to antifungal treatment or recurrent infections. Copyright © 2011 Elsevier B.V. All rights reserved.
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Dandruff: Lifestyle and Home Remedies
... can often help mild dandruff. When regular shampoos fail, dandruff shampoos you can buy at a drugstore ... antifungal agent that may work when other shampoos fail. It's available over-the-counter as well as ...
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Antifungal susceptibility testing of Malassezia yeast: comparison of two different methodologies.
Rojas, Florencia D; Córdoba, Susana B; de Los Ángeles Sosa, María; Zalazar, Laura C; Fernández, Mariana S; Cattana, María E; Alegre, Liliana R; Carrillo-Muñoz, Alfonso J; Giusiano, Gustavo E
2017-02-01
All Malassezia species are lipophilic; thus, modifications are required in susceptibility testing methods to ensure their growth. Antifungal susceptibility of Malassezia species using agar and broth dilution methods has been studied. Currently, few tests using disc diffusion methods are being performed. The aim was to evaluate the in vitro susceptibility of Malassezia yeast against antifungal agents using broth microdilution and disc diffusion methods, then to compare both methodologies. Fifty Malassezia isolates were studied. Microdilution method was performed as described in reference document and agar diffusion test was performed using antifungal tablets and discs. To support growth, culture media were supplemented. To correlate methods, linear regression analysis and categorical agreement was determined. The strongest linear association was observed for fluconazole and miconazole. The highest agreement between both methods was observed for itraconazole and voriconazole and the lowest for amphotericin B and fluconazole. Although modifications made to disc diffusion method allowed to obtain susceptibility data for Malassezia yeast, variables cannot be associated through a linear correlation model, indicating that inhibition zone values cannot predict MIC value. According to the results, disc diffusion assay may not represent an alternative to determine antifungal susceptibility of Malassezia yeast. © 2016 Blackwell Verlag GmbH.
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Furfural from Pine Needle Extract Inhibits the Growth of a Plant Pathogenic Fungus, Alternaria mali
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
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In vitro susceptibility and multilocus sequence typing of Fusarium isolates causing keratitis.
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.
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De-la-Torre, Janire; Ortiz-Samperio, María Esther; Marcos-Arias, Cristina; Marichalar-Mendia, Xabier; Eraso, Elena; Echebarria-Goicouria, María Ángeles; Aguirre-Urizar, José Manuel; Quindós, Guillermo
2017-06-01
Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.
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Evaluation of antifungal volatile compounds on the basis of the elongation rate of a single hypha.
Matsuoka, H; Ii, Y; Takekawa, Y; Teraoka, T
1990-01-01
A novel method is proposed for the evaluation of the activity of an antifungal agent administered as a gas. This system is composed of a batch-flow type reaction vessel, a gas flow system, and a microscopic observation system. The agar plate was prepared on the ceiling of the reaction vessel, and the mycelium of a fungus (Aspergillus niger or Rhizoctonia solani) was inoculated onto it. After preincubation at 25 degrees C for 24 h, the reaction vessel was connected to the gas flow system. An appropriate hypha was selected, and its elongation rate was measured. Then a sample holder containing an antifungal compound was inserted into the reaction vessel from the side hole to saturate the atmosphere inside with its vapor. The retardation or inhibition of the hypha elongation was observed on a television monitor and recorded on a video tape recorder. The antifungal compound was then removed, and the reaction vessel was flushed with air. If the hypha lived, it began to elongate again. By this method, antifungal activity of seven odor compounds could be evaluated quantitatively within several hours. Images PMID:2082824
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Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?
Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus
2016-01-01
Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288
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Khidre, Rizk E; Abu-Hashem, Ameen A; El-Shazly, Mohamed
2011-10-01
A new series of 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile such as hydrazide hydrazones 3a-h; ethane-1,2-diaminopyridine 6; phthalimidopyridines 8a,b; hydrazides 10a,b; urea 11a and thiourea 11b were synthesized in a good to excellent yield in step efficient process, using 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (1) as a key intermediate. The antibacterial and antifungal activities of the synthesized compounds were evaluated. The obtained data indicated that the majority of the tested compounds exhibited both antibacterial and antifungal activities, particularly compounds 8a and 8b showed a comparable effect to a well known antibacterial and antifungal agents. Published by Elsevier Masson SAS.
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Ansari, Anam; Ali, Abad; Asif, Mohd; Rauf, Mohd Ahmar; Owais, Mohammad; Shamsuzzaman
2018-06-01
A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents. Copyright © 2018 Elsevier Inc. All rights reserved.
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Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Maroszyńska, Marta
2017-01-01
Candida spp. cause significant health problems, inducing various types of superficial and deep-seated mycoses in humans. As a result of the increasing antibiotic resistance among pathogenic yeasts, the interest in alternative agents of antifungal activity is growing. This study evaluated the antimicrobial activity of selected essential oils (EOs) against Candida clinical and food-borne strains, including antibiotic-resistant isolates, in relation to yeast cell surface hydrophobicity (CSH). Candida strains showed different range of susceptibility to tea tree, thyme, peppermint, and clove oils, and peppermint oil demonstrated the lowest anticandidal activity with minimal inhibitory concentrations (MICs) of 0.03-8.0% v/v. MIC values for thyme and clove oils ranged from 0.03% to 0.25% v/v, and for tea tree oil-from 0.12% to 2.0% v/v. The exception was Candida tropicalis food-borne strain, the growth of which was inhibited after application of EOs at concentration of 8% v/v. Due to diverse yeast susceptibility to EOs, isolates were divided into five clusters in a principal component analysis model, each containing both clinical and food-borne strains. Hydrophobic properties of yeast were also diversified, and 37% of clinical and 50% of food-borne strains exhibited high hydrophobicity. The study indicates high homology of clinical and food-borne Candida isolates in relation to their susceptibility to anticandidal agents and hydrophobic properties. The susceptibility of yeasts to EOs could be partially related to their CSH. High antifungal activity of examined EOs, also against antibiotic-resistant isolates, indicates their usefulness as agents preventing the development of Candida strains of different origin.
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The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats
2013-01-01
Background Otomycosis is defined as an infection of the external ear canal with fungal agents. The treatment of the disease is cleansing and drying of the external ear canal, identification and treatment of any predisposing factors and application of topical antifungal agents. Terbinafine is used as an antifungal agent to treat otomycosis. We proposed to investigate the probable ototoxic effect of terbinafine solution on auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) when applied intratympanically in the middle ear of rats. Methods The experiment was performed on 30 female Wistar albino rats. Thirty animals were divided into three groups of 10 animals each. 1% terbinafine solution was administered to the first group (group T). The second group (group G) was administered 40 mg/ml gentamicin solution (ototoxic control). The third group (group S) was administered saline solution (negative control). Baseline DPOAE measurements and ABR testing from the left ears were obtained from the animals in all groups under general anesthesia. Ear solutions were applied in the middle ear intratympanically with a dental needle. Treatment was initiated after baseline measurements and repeated once every two days for fifteen days. Results Pre and post-treatment DPOAE responses for all tested frequencies of group T and Group S showed no statistically significant difference. However, the group G demonstrated a significant change in ABR thresholds and DPOAE responses. Conclusions Terbinafine solution is a broad spectrum antifungal agent effective in the treatment of otomycosis. The present study demonstrated that its direct administration in the middle ear of rats does not affect inner ear function as measured by ABR and DPOAE responses. PMID:23663536
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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
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NASA Astrophysics Data System (ADS)
Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi
2016-01-01
Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07918g
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Kikuchi, Izumi; Morimoto, Kensuke; Kawana, Seiji; Tanuma, Hiroyuki
2006-01-01
Potassium iodide, itraconazole (ITCZ), and terbinafine are widely known as oral antifungal agents for the treatment of sporotrichosis. Although potassium iodide has been used as the antifungal agent of first choice in Japan due to its high efficacy, its use is not covered by the health insurance programs. In this report, we present the disease course of 3 patients with sporotrichosis in which ITCZ was remarkably effective. By reviewing cases reported in the past, we found sufficient therapeutic effects of ITCZ against sporotrichosis. We also conducted a simple comparison of the efficacy of ITCZ in clinical trials with that of its post-market release; finding the latter to be lower. This seems to be attributable to the problem of compliance or the administration method.
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Oliveira, V M; Khalil, N M; Carraro, E
2018-02-01
Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting 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 black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.
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Gharamah, Abdullah A; Moharram, Ahmed M; Ismail, Mady A; AL-Hussaini, Ashraf K
2014-01-01
Purpose: This work was conducted to study the ability of bacterial and fungal isolates from keratitis cases in Upper Egypt to produce enzymes, toxins, and to test the isolated fungal species sensitivity to some therapeutic agents. Materials and Methods: One hundred and fifteen patients clinically diagnosed to have microbial keratitis were investigated. From these cases, 37 bacterial isolates and 25 fungal isolates were screened for their ability to produce extra-cellular enzymes in solid media. In addition, the ability of fungal isolates to produce mycotoxins and their sensitivity to 4 antifungal agents were tested. Results: Protease, lipase, hemolysins, urease, phosphatase, and catalase were detected respectively in 48.65%, 37.84%, 59.46%, 43.24%, 67.57%, and 100% out of 37 bacterial isolates tested. Out of 25 fungal isolates tested during the present study, 80% were positive for protease, 84% for lipase and urease, 28% for blood hemolysis, and 100% for phosphatase and catalase enzymes. Thirteen fungal isolates were able to produce detectable amounts of 7 mycotoxins in culture medium (aflatoxins (B1, B2, G1, and G2), sterigmatocystin, fumagillin, diacetoxyscirpenol, zearalenone, T-2 toxin, and trichodermin). Among the antifungal agents tested in this study, terbinafine showed the highest effect against most isolates in vitro. Conclusion: In conclusion, the ability of bacterial and fungal isolates to produce extracellular enzymes and toxins may be aid in the invasion and destruction of eye tissues, which, in turn, lead to vision loss. PMID:24008795
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Yeast Colonization and Drug Susceptibility Pattern in the Pediatric Patients With Neutropenia
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
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Evidence-Based Guidelines for Empirical Therapy of Neutropenic Fever in Korea
Kim, Sung-Han; Kim, Soo Young; Kim, Chung-Jong; Park, Wan Beom; Song, Young Goo; Choi, Jung-Hyun
2011-01-01
Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3-5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers. PMID:21716917
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Chouvenc, Thomas; Su, Nan-Yao
2010-08-01
The use of entomopathogens for biological control of subterranean termites (Rhinotermitidae) has attracted attention in the past four decades, and several laboratory studies have shown promising results with fungal agents. This approach was based on the concept of classical biological control with the use of a virulent agent that can self-replicate in a termite nest and be transmitted among individuals, resulting in an epizootic to kill the entire colony. However, the absence of positive results in field studies challenged the potential of fungal pathogens as a realistic approach for subterranean termite control, and the relationship between fungi and subterranean termites remains poorly understood. A multimodal approach of the currently identified defense mechanisms allowed us to show that subterranean termites have the ability to prevent an epizootic from occurring. The defense mechanisms involved in such resistance are reviewed and documented. Finally, the interactions among three major defense mechanisms (grooming, cellular encapsulation, and gut antifungal activity) were analyzed, and it is suggested that these mechanisms act synergistically to produce an efficient defense against the infection of the fungus at the individual and group level so as to protect the colony from epizootics.
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Essential Oil from Piper aduncum: Chemical Analysis, Antimicrobial Assessment, and Literature Review
Monzote, Lianet; Scull, Ramón; Cos, Paul; Setzer, William N.
2017-01-01
Background: The challenge in antimicrobial chemotherapy is to find safe and selective agents with potency that will not be compromised by previously developed resistance. Terrestrial plants could provide new leads to antibacterial, antifungal, or antiprotozoal activity. Methods: The essential oil (EO) of Piper aduncum L. (Piperaceae) from Cuba was analyzed by gas chromatography—mass spectrometry (GC-MS). A cluster analysis of P. aduncum EO compositions reported in the literature was carried out. The EO was screened against a panel of microorganisms (bacteria, fungi, parasitic protozoa) as well as for cytotoxicity against human cells. In addition, a review of scientific literature and a bibliometric study was also conducted. Results: A total of 90 compounds were identified in the EO, of which camphor (17.1%), viridiflorol (14.5%), and piperitone (23.7%) were the main components. The cluster analysis revealed at least nine different chemotypes. The EO did not show notable activity against bacteria or fungi, but was active against parasitic protozoa. Conclusions: The results from this study indicate P. aduncum from Cuba is a unique chemotype, support the importance of P. aduncum EOs as medicines, and demonstrate the promise of Cuban P. aduncum EO as a chemotherapeutic agent against parasitic protozoal infections. PMID:28930264
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Monzote, Lianet; Scull, Ramón; Cos, Paul; Setzer, William N
2017-07-02
Background: The challenge in antimicrobial chemotherapy is to find safe and selective agents with potency that will not be compromised by previously developed resistance. Terrestrial plants could provide new leads to antibacterial, antifungal, or antiprotozoal activity. Methods: The essential oil (EO) of Piper aduncum L. (Piperaceae) from Cuba was analyzed by gas chromatography-mass spectrometry (GC-MS). A cluster analysis of P. aduncum EO compositions reported in the literature was carried out. The EO was screened against a panel of microorganisms (bacteria, fungi, parasitic protozoa) as well as for cytotoxicity against human cells. In addition, a review of scientific literature and a bibliometric study was also conducted. Results: A total of 90 compounds were identified in the EO, of which camphor (17.1%), viridiflorol (14.5%), and piperitone (23.7%) were the main components. The cluster analysis revealed at least nine different chemotypes. The EO did not show notable activity against bacteria or fungi, but was active against parasitic protozoa. Conclusions: The results from this study indicate P. aduncum from Cuba is a unique chemotype, support the importance of P. aduncum EOs as medicines, and demonstrate the promise of Cuban P. aduncum EO as a chemotherapeutic agent against parasitic protozoal infections.
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Grzesiak, B; Krukowski, H; Głowacka, A
2018-04-16
The research concerns algae of the genus Prototheca. They are found in the natural environment and they can cause a disease in animals and humans called protothecosis. The aim of the study was to evaluate the in vitro activity of the fruit and vegetable rinse agent SunSmile ® Fruit & Vegetable Rinse (Sunrider International) against P. zopfii isolates. The materials consisted of ten P. zopfii strains isolated from the milk of cows with mastitis. The following antifungal chemotherapeutic agents were also used in the study for comparison: nystatin, ketoconazole, amphothericin B, miconazole, clotrimazole, econazole, fluconazole, and flucytosine. The tube dilution method were used to evaluate the effect of a fruit and vegetable rinse agent and the disc-diffusion method to evaluate the effect of antifungal chemotherapeutic agents on P. zopfii strains. All tested strains of P. zopfii were susceptible to the action of the SunSmile ® agent. The MMC was in the range of 0.0024-0.0190%. The SunSmile ® Fruit & Vegetable Rinse can be used in prevention of mastitis in cows and in human protothecosis due to its safe, natural composition and efficacy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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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.
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Inhibition of Propionibacterium acnes lipase activity by the antifungal agent ketoconazole.
Unno, Mizuki; Cho, Otomi; Sugita, Takashi
2017-01-01
The common skin disease acne vulgaris is caused by Propionibacterium acnes. A lipase secreted by this microorganism metabolizes sebum and the resulting metabolites evoke inflammation in human skin. The antifungal drug ketoconazole inhibits P. acnes lipase activity. We previously showed that the drug also inhibits the growth of P. acnes. Thus, ketoconazole may serve as an alternative treatment for acne vulgaris, which is important because the number of antibiotic-resistant P. acnes strains has been increasing. © 2017 The Societies and John Wiley & Sons Australia, Ltd.
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A Global Declaration on Appropriate Use of Antimicrobial Agents across the Surgical Pathway.
This declaration, signed by an interdisciplinary task force of 234 experts from 83 different countries with different backgrounds, highlights the threat posed by antimicrobial resistance and the need for appropriate use of antibiotic agents and antifungal agents in hospitals worldwide especially focusing on surgical infections. As such, it is our intent to raise awareness among healthcare workers and improve antimicrobial prescribing. To facilitate its dissemination, the declaration was translated in different languages.
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Van Gerven, F; Odds, F C
1995-01-01
Bifonazole, clotrimazole, flutrimazole, ketoconazole, miconazole and sertaconazole were tested for their activity against 23 isolates of Malassezia furfur by agar dilution in vitro. Topical formulations of the same agents were evaluated for efficacy against M. furfur skin infections in guinea pigs in vivo. The most potent inhibitor in vitro was ketoconazole (geometric mean minimum inhibitory concentration 0.51 microgram ml-1), followed by bifonazole (8.1 micrograms ml-1), then miconazole (14 micrograms ml-1), clotrimazole (15 micrograms ml-1) and flutrimazole (16 micrograms ml-1), with sertaconazole the least active (52 micrograms ml-1). In animal experiments involving three consecutive days of topical treatments, bifonazole 1% cream, clotrimazole 1% cream, flutrimazole 1% and 2% creams, ketoconazole 2% cream and shampoo and miconazole 2% cream all reduced M. furfur dermatitis lesion severity below that of untreated control animals; however, sertaconazole 2% gel and cream showed no reduction in lesion severity below control. The results confirm that ketoconazole is a more potent inhibitor of M. furfur in vitro than other topical antifungal agents of its class and suggest that sertaconazole is the least effective of such agents among those tested.
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Water quality and antifungal susceptibility of opportunistic yeast pathogens from rivers.
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.
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Training should be the first step toward an antifungal stewardship program.
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.
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Luo, Ze-Ping; Lin, Hai-Yan; Ding, Wen-Bing; He, Hua-Liang
2015-01-01
Sixty-one endophytic fungus strains with different colony morphologies were isolated from the leaves, stems and roots of Tephrosia purpurea with colonization rates of 66.95%, 37.50%, and 26.92%, respectively. Based on internal transcribed spacer sequence analysis, 61 isolates were classified into 16 genera belonging to 3 classes under the phylum Ascomycota. Of the 61 isolates, 6 (9.84%) exhibited antifungal activity against one or more indicator plant pathogenic fungi according to the dual culture test. Isolate TPL25 had the broadest antifungal spectrum of activity, and isolate TPL35 was active against 5 plant pathogenic fungi. Furthermore, culture filtrates of TPL25 and TPL35 exhibited greater than 80% growth inhibition against Sclerotinia sclerotiorum. We conclude that the endophytic fungal strains TPL25 and TPL35 are promising sources of bioactive compounds. PMID:26839503
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Plants from Lamiaceae family as source of antifungal molecules in humane and veterinary medicine.
Waller, Stefanie Bressan; Cleff, Marlete Brum; Serra, Emanoele Figueiredo; Silva, Anna Luiza; Gomes, Angelita Dos Reis; de Mello, João Roberto Braga; de Faria, Renata Osório; Meireles, Mário Carlos Araújo
2017-03-01
This work aimed to review the main plants of Lamiaceae family with activity against pathogenic fungi of medical and veterinary interest. Published studies in the main international databases between January 2002 and June 2016 showed that 55 botanical species belonging to 27 genus presented antifungal activity in different forms of extractions, mainly essential oils. Pathogenic fungi of Aspergillus spp., Candida spp., Malassezia spp., Cryptococcus spp., Sporothrix spp., Microsporum spp., Trichophyton spp. and Epidermophyton spp. genus were in vitro sensitive to several plants of Lamiaceae family. Chemical molecules isolated were described as promising use as antifungals in mycoses, highlighting estragole, 1,8-cineole, terpineol-4, γ-terpinene, among others. However, it should be alert to need of universal standardization in the laboratories tests with natural products. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Tale, Rajesh H; Rodge, Atish H; Hatnapure, Girish D; Keche, Ashish P
2011-08-01
A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Bigineli's reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 μM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 μg/mL against selected pathogenic bacteria and fungi. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Tafi, Andrea; Costi, Roberta; Botta, Maurizio; Di Santo, Roberto; Corelli, Federico; Massa, Silvio; Ciacci, Andrea; Manetti, Fabrizio; Artico, Marino
2002-06-20
The synthesis, anti-Candida activity, and quantitative structure-activity relationship (QSAR) studies of a series of 2,4-dichlorobenzylimidazole derivatives having a phenylpyrrole moiety (related to the antibiotic pyrrolnitrin) in the alpha-position are reported. A number of substituents on the phenyl ring, ranging from hydrophobic (tert-butyl, phenyl, or 1-pyrrolyl moiety) to basic (NH(2)), polar (CF(3), CN, SCH(3), NO(2)), or hydrogen bond donors and acceptor (OH) groups, were chosen to better understand the interaction of these compounds with cytochrome P450 14-alpha-lanosterol demethylase (P450(14DM)). Finally, the triazole counterpart of one of the imidazole compounds was synthesized and tested to investigate influence of the heterocyclic ring on biological activity. The in vitro antifungal activities of the newly synthesized azoles 10p-v,x-c' were tested against Candida albicans and Candida spp. at pH 7.2 and pH 5.6. A CoMFA model, previously derived for a series of antifungal agents belonging to chemically diverse families related to bifonazole, was applied to the new products. Because the results produced by this approach were not encouraging, Catalyst software was chosen to perform a new 3D-QSAR study. Catalyst was preferred this time because of the possibility of considering each compound as a collection of energetically reasonable conformations and of considering alternative stereoisomers. The pharmacophore model developed by Catalyst, named HYPO1, showed good performances in predicting the biological activity data, although it did not exhibit an unequivocal preference for one enantiomeric series of inhibitors relative to the other. One aromatic nitrogen with a lone pair in the ring plane (mapped by all of the considered compounds) and three aromatic ring features were recognized to have pharmacophoric relevance, whereas neither hydrogen bond acceptor nor hydrophobic features were found. These findings confirmed that the key interaction of azole antifungals with the demethylase enzyme is the coordination bond to the iron ion of the porphyrin system, while interactions with amino acids localized in proximity of heme could modulate the biological activity of diverse antifungal agents. In conclusion, HYPO1 conveys important information in an intuitive manner and can provide predictive capability for evaluating new compounds.
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El-Azizi, Mohamed; Farag, Noha; Khardori, Nancy
2015-04-03
Candida albicans is a common cause of a variety of superficial and invasive disseminated infections the majority of which are associated with biofilm growth on implanted devices. The aim of the study is to evaluate the activity of amphotericin B and voriconazole against the biofilm and the biofilm-dispersed cells of Candida albicans using a newly developed in vitro pharmacokinetic model which simulates the clinical situation when the antifungal agents are administered intermittently. RPMI medium containing 1-5 X 10(6) CFU/ml of C. albicans was continuously delivered to the device at 30 ml/h for 2 hours. The planktonic cells were removed and biofilms on the catheter were kept under continuous flow of RPMI medium at 10 ml/h. Five doses of amphotericin B or voriconazole were delivered to 2, 5 and 10 day-old biofilms at initial concentrations (2 and 3 μg/ml respectively) that were exponentially diluted. Dispersed cells in effluents from the device were counted and the adherent cells on the catheter were evaluated after 48 h of the last dose. The minimum inhibitory concentration of voriconazole and amphotericin B against the tested isolate was 0.0325 and 0.25 μg/ml respectively. Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm. The log10 reduction in the dispersed cells was 2.54-3.54, 2.30-3.55, and 1.94-2.50 following addition of 5 doses of amphotericin B to 2-, 5- and 10-day old biofilms respectively. The number of the viable cells within the biofilm was reduced by 18 (±7.63), 5 and 4% following addition of the 5 doses of amphotericin B to the biofilms respectively. Voriconazole showed no significant effect on the viability of C. albicans within the biofilm. Both antifungal agents failed to eradicate C. albicans biofilm or stop cell dispersion from them and the resistance progressed with maturation of the biofilm. These findings go along with the need for removal of devices in spite of antifungal therapy in patients with device-related infection. This is the first study which investigates the effects of antifungal agents on the biofilm and biofilm-dispersion of C. albicans in an in vitro pharmacokinetic biofilm model.
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Schmourlo, Gracilene; Mendonça-Filho, Ricardo R; Alviano, Celuta Sales; Costa, Sônia S
2005-01-15
In the search for bioactive compounds, bioautography and ethanol precipitation of macromolecules (proteins, polysaccharides, etc.) of plant aqueous extracts were associated in an antifungal screening. Thus, the supernatants, precipitates (obtained by ethanol precipitation) and aqueous extracts were investigated of medicinal and fruit bearing plants used against skin diseases by the Brazilian population. The agar diffusion and broth dilution methods were used to assess the activity against three fungi: Candida albicans, Trichophyton rubrum and Cryptococcus neoformans. The results, evaluated by the diameter of the inhibition zone of fungal growth, indicate that six plant species, among the 16 investigated, showed significant antifungal activity. The minimal inhibitory concentration (MIC) was determined on plant extracts that showed high efficacy against the tested microorganisms. The most susceptible yeast was Trichophyton rubrum and the best antifungal activity was shown by Xanthosoma sagittifolium supernatant. The bioautography was performed only for the aqueous extracts and supernatants of those plants that showed antifungal activity against Candida albicans and Cryptococcus neoformans, using n-butanol/acetic acid/water (BAW) 8:1:1 to develop silica gel TLC plates. Clear inhibition zones were observed for aqueous extracts of Schinus molle (R(f) 0.89) and Schinus terebinthifolius (R(f) 0.80) against Candida albicans, as for supernatant of Anacardium occidentale (R(f) 0.31) against Cryptococcus neoformans. The separation of macromolecules from metabolites, as in the case of Anacardium occidentale, Solanum sp. and Xanthosoma sagittifolium, enhances antifungal activity. In other cases, the antifungal activity is destroyed, as observed for Momordica charantia, Schinus molle and Schinus terebinthifolius.
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MacCallum, D M; Desbois, A P; Coote, P J
2013-08-01
The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections.
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Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales
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
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Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales.
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.
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Kumar, Neeraj; Shishu
2015-01-25
The study aims to statistically develop a microemulsion system of an antifungal agent, itraconazole for overcoming the shortcomings and adverse effects of currently used therapies. Following preformulation studies like solubility determination, component selection and pseudoternary phase diagram construction, a 3-factor D-optimal mixture design was used for optimizing a microemulsion having desirable formulation characteristics. The factors studied for sixteen experimental trials were percent contents (w/w) of water, oil and surfactant, whereas the responses investigated were globule size, transmittance, drug skin retention and drug skin permeation in 6h. Optimized microemulsion (OPT-ME) was incorporated in Carbopol based hydrogel to improve topical applicability. Physical characterization of the formulations was performed using particle size analysis, transmission electron microscopy, texture analysis and rheology behavior. Ex vivo studies carried out in Wistar rat skin depicted that the optimized formulation enhanced drug skin retention and permeation in 6h in comparison to conventional cream and Capmul 908P oil solution of itraconazole. The in vivo evaluation of optimized formulation was performed using a standardized Tinea pedis model in Wistar rats and the results of the pharmacodynamic study, obtained in terms of physical manifestations, fungal-burden score, histopathological profiles and oxidative stress. Rapid remission of Tinea pedis from rats treated with OPT-ME formulation was observed in comparison to commercially available therapies (ketoconazole cream and oral itraconazole solution), thereby indicating the superiority of microemulsion hydrogel formulation over conventional approaches for treating superficial fungal infections. The formulation was stable for a period of twelve months under refrigeration and ambient temperature conditions. All results, therefore, suggest that the OPT-ME can prove to be a promising and rapid alternative to conventional antifungal therapies against superficial fungal infections. Copyright © 2014 Elsevier B.V. All rights reserved.
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Rachitha, P.; Krupashree, K.; Jayashree, G. V.; Gopalan, Natarajan; Khanum, Farhath
2017-01-01
Objective: The aim of this study is to determine the phytochemical composition, antifungal activity of Mentha piperita essential oil (MPE) against Fusarium sporotrichioides. Methods: The phytochemical composition was conducted by gas chromatography mass spectrometry (GC MS) analysis and mycelia growth inhibition was determined by minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), the morphological characterization was observed by scanning electron microscopy. Finally, the membrane permeability was determined by the release of extracellular constituents, pH, and total lipid content. Result: In GC MS analysis, 22 metabolites were identified such as menthol, l menthone, pulegone, piperitone, caryophyllene, menthol acetate, etc. The antifungal activity against targeted pathogen, with MIC and MFC 500 μg/mL and 1000 μg/mL, respectively. The MPE altered the morphology of F. sporotrichoides hyphae with the loss of cytoplasm content and contorted the mycelia. The increasing concentration of MPE showed increase in membrane permeability of F. sporotrichoides as evidenced by the release of extracellular constituents and pH with the disruption of cell membrane indicating decrease in lipid content of F. sporotrichoides. Conclusion: The observed results showed that MPE exhibited promising new antifungal agent against Fusarium sporotrichioides. SUMMARY F. sporotrichioides, filamentous fungi contaminate to corn and corn--based productsF. sporotrichioides mainly responsible for the production of T-2 toxinPhytochemical composition was conducted by gas chromatography--mass spectrometry analysisMentha piperita essential oil (MPE) is commonly known as peppermintThe F. sporotrichioides growth was inhibited by MPE (minimum inhibitory concentration, minimum fungicidal concentration)Morphological observation by scanning electron microscope. Abbreviations Used: Cfu: Colony forming unit; DMSO: Dimethyl sulfoxide, °C: Degree celsius; F. Sporotrichoides: Fusarium sporotrichioides; EOs: Essential oils; M: Molar, g: Gram/gravity, mg: Milligram; μg: Microgram, ml: Milliliter; mm: Millimeter, min: Minutes; M. piperita: Mentha piperita, MIC: Minimum inhibitory concentration; MFC: Minimum fungicidal concentration; MAE: Mentha arvensis essential oil; Na2SO4: Sodium sulfate; pH: Potential Hydrogen; PDB: Potato Dextrose Broth; SEM: Scanning electron microscope PMID:28250658
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Contact killing and antimicrobial properties of copper.
Vincent, M; Duval, R E; Hartemann, P; Engels-Deutsch, M
2018-05-01
With the emergence of antibiotic resistance, the interest for antimicrobial agents has recently increased again in public health. Copper was recognized in 2008 by the United States Environmental Protection Agency (EPA) as the first metallic antimicrobial agent. This led to many investigations of the various properties of copper as an antibacterial, antifungal and antiviral agent. This review summarizes the latest findings about 'contact killing', the mechanism of action of copper nanoparticles and the different ways micro-organisms develop resistance to copper. © 2017 The Society for Applied Microbiology.
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Wang, Hui; Jiang, Mingyue; Li, Shujun; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo
2017-09-01
Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger ( A. niger ) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models ( R 2 = 0.9346 for A. niger , R 2 = 0.9590 for P. citrinum, ) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.
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Antibacterial, antifungal, and antiviral activities of the lipophylic extracts of Pistacia vera.
Ozçelik, Berrin; Aslan, Mustafa; Orhan, Ilkay; Karaoglu, Taner
2005-01-01
In the present study, antibacterial, antifungal, and antiviral properties of 15 lipohylic extracts obtained from different parts (leaf, branch, stem, kernel, shell skins, seeds) of Pistacia vera were screened against both standard and the isolated strains of Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. parapsilosis by microdilution method. Both Herpes simplex (DNA) and Parainfluenza viruses (RNA) were used for the determination of antiviral activity of the P. vera extracts by using Vero cell line. Ampicilline, ofloxocine, ketoconazole, fluconazole, acyclovir and oseltamivir were used as the control agents. The extracts showed little antibacterial activity between the range of 128-256 microg/ml concentrations whereas they had noticeable antifungal activity at the same concentrations. Kernel and seed extracts showed significant antiviral activity compared to the rest of the extracts as well as the controls.
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Wang, Hui; Jiang, Mingyue; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo
2017-01-01
Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID:28989758
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Inhibitors of amino acids biosynthesis as antifungal agents.
Jastrzębowska, Kamila; Gabriel, Iwona
2015-02-01
Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.
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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.
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Ketoconazole, an antifungal agent, protects against adiposity induced by a cafeteria diet.
Campión, J; Martínez, J A
2004-07-01
Ketoconazole, an anti-glucocorticoid agent, is widely used in humans as an antifungal agent. It inhibits ergosterol synthesis and reduces cortisol levels in the treatment of Cushing's Syndrome. The aim of this work was to study the drug's preventive potential against adiposity induced by a high-fat cafeteria diet in rats. Female Wistar rats were fed on standard pelleted diet or cafeteria diet during 42 days in the presence or absence of an oral treatment with ketoconazole (24 mg/kg of body weight). The cafeteria diet increased energy intake and body weight. In addition, this high-fat diet increased body-fat weight and adipose tissue depots analyzed. Interestingly, ketoconazole was able to protect against increased total body fat and adipose depot enlargement induced after cafeteria-diet feeding. Moreover, ex vivo isoproterenol-induced lipolysis was reduced in adipocytes from cafeteria-fed animals; this decrease was reverted by treatment with ketoconazole. Thus, ketoconazole was able to protect against adiposity induced by a cafeteria diet, revealing an interaction between fat intake and glucocorticoids on adipose deposition.
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Pagani, Danielle M; Heidrich, Daiane; Paulino, Gustavo V B; de Oliveira Alves, Karine; Dalbem, Paula T; de Oliveira, Caroline F; Andrade, Zélia M M; Silva, Carolini; Correia, Monica D; Scroferneker, Maria Lúcia; Valente, Patricia; Landell, Melissa Fontes
2016-12-01
Candida is a common fungus with the capacity to cause infections in humans. However, most studies have concentrated on clinical isolates and little is known about the identity, ecology and drug resistance of free living species/strains. Here, we isolate eight strains of Candida haemulonii and four strains of Cutaneotrichosporon dermatis from three marine cnidarian zoanthids species (Palythoa caribaeorum, Palythoa variabilis and Zoanthus sociatus) collected from Brazilian coral reefs. Strains were identified by sequencing of the D1/D2 domain LSU rDNA and ITS region. We tested these environmental isolates for their capacity to grow in media with increasing concentration of NaCl, capacity to grow in different temperatures, enzymatic activity and antifungal susceptibility. For C. haemulonii, all strains strongly produced gelatinase, esterase and albuminase and were either able to express lipase, phospholipase and keratinase, but not express urease and DNase. The strains were able to grow at 37 °C, but not at 39 °C, and except for LMS 40, all of them could grow in a 10 % NaCl medium. All isolates were resistant to all antifungals tested, with exception for ketoconazole and tioconazole (MIC = 2 µg/mL). For C. dermatis, all strains could grow at 39 °C and could not express phospholipase, keratinase or gelatinase. However, all were capable of expressing urease, lipase and esterase. Three out of four strains could grow in a 10 % NaCl medium, but none grew in a 30 % NaCl medium. The strains showed high values of minimal inhibitory concentration. LMPV 90 was resistant to tioconazole, terbinafine, fluconazole and posaconazole, and LMS 38 was resistant to all antifungal agents tested. We discuss the characterization of C. haemulonii and C. dermatis as a possible emerging pathogen due to its animal-related enzymatic arsenal and antifungal resistance.
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Ishida, Kelly; Fernandes Rodrigues, Juliany Cola; Cammerer, Simon; Urbina, Julio A; Gilbert, Ian; de Souza, Wanderley; Rozental, Sonia
2011-01-21
Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains. Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy. The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy)-phenyl}]-quinuclidine-2-ene) (WSP1267) had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a) loss of cell wall integrity, (b) detachment of the plasma membrane from the fungal cell wall, (c) accumulation of small vesicles in the periplasmic region, (d) presence of large electron-dense vacuoles and (e) significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei. Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new antifungal drugs.
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Topical anti-infective sinonasal irrigations: update and literature review.
Lee, Jivianne T; Chiu, Alexander G
2014-01-01
Sinonasal anti-infective irrigations have emerged as a promising therapeutic modality in the comprehensive management of chronic rhinosinusitis (CRS), particularly in the context of recalcitrant disease. The purpose of this article was to delineate the current spectrum of topical anti-infective therapies available and evaluate their role in the treatment of CRS. A systematic literature review was performed on all studies investigating the use of topical antimicrobial solutions in the medical therapy of CRS. Anti-infective irrigations were stratified into topical antibacterial, antifungal, and additive preparations according to their composition and respective microbicidal properties. The use of topical antibiotic irrigations has been supported by low-level studies in the treatment of refractory CRS, with optimal results achieved in patients who have undergone prior functional endoscopic sinus surgery and received culture-directed therapy. Multiple evidence-based reviews have not established any clinical benefit with the administration of topical antifungals, and their use is not currently recommended in the management of routine CRS. Topical additives including surfactants may be beneficial as adjunctive treatment for recalcitrant CRS, but additional research is needed to investigate their efficacy in comparison with other agents and establish safety profiles. Topical anti-infective solutions are not recommended as first-line therapy for routine CRS but may be considered as a potential option for patients with refractory CRS who have failed traditional medical and surgical intervention. Additional research is necessary to determine which patient populations would derive the most benefit from each respective irrigation regimen and identify potential toxicities associated with prolonged use.
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A Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance
Taff, Heather T.; Nett, Jeniel E.; Zarnowski, Robert; Ross, Kelly M.; Sanchez, Hiram; Cain, Mike T.; Hamaker, Jessica; Mitchell, Aaron P.; Andes, David R.
2012-01-01
Extracellular polysaccharides are key constituents of the biofilm matrix of many microorganisms. One critical carbohydrate component of Candida albicans biofilms, β-1,3 glucan, has been linked to biofilm protection from antifungal agents. In this study, we identify three glucan modification enzymes that function to deliver glucan from the cell to the extracellular matrix. These enzymes include two predicted glucan transferases and an exo-glucanase, encoded by BGL2, PHR1, and XOG1, respectively. We show that the enzymes are crucial for both delivery of β-1,3 glucan to the biofilm matrix and for accumulation of mature matrix biomass. The enzymes do not appear to impact cell wall glucan content of biofilm cells, nor are they necessary for filamentation or biofilm formation. We demonstrate that mutants lacking these genes exhibit enhanced susceptibility to the commonly used antifungal, fluconazole, during biofilm growth only. Transcriptional analysis and biofilm phenotypes of strains with multiple mutations suggest that these enzymes act in a complementary fashion to distribute matrix downstream of the primary β-1,3 glucan synthase encoded by FKS1. Furthermore, our observations suggest that this matrix delivery pathway works independently from the C. albicans ZAP1 matrix formation regulatory pathway. These glucan modification enzymes appear to play a biofilm-specific role in mediating the delivery and organization of mature biofilm matrix. We propose that the discovery of inhibitors for these enzymes would provide promising anti-biofilm therapeutics. PMID:22876186
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, J.; Bolstad, D; Smith, A
2008-01-01
Candida glabrata is a lethal fungal pathogen resistant to many antifungal agents and has emerged as a critical target for drug discovery. Over the past several years, we have been developing a class of propargyl-linked antifolates as antimicrobials and hypothesized that these compounds could be effective inhibitors of dihydrofolate reductase (DHFR) from C. glabrata. We initially screened a small collection of these inhibitors and found modest levels of potency. Subsequently, we determined the crystal structure of C. glabrata DHFR bound to a representative inhibitor with data to 1.6 A resolution. Using this structure, we designed and synthesized second-generation inhibitors. Thesemore » inhibitors bind the C. glabrata DHFR enzyme with subnanomolar potency, display greater than 2000-fold levels of selectivity over the human enzyme, and inhibit the growth of C. glabrata at levels observed with clinically employed therapeutics.« less
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Metabolism of Tryptophans by Pseudomonas aureofaciens
Elander, Richard P.; Mabe, James A.; Hamill, Robert H.; Gorman, Marvin
1968-01-01
Twenty-nine strains of Pseudomonas, classified as P. fluorescens biotype D or E or as P. multivorans, were examined for the production of pyrrolnitrin, an antifungal agent synthesized in P. aureofaciens. Eight strains were shown to produce pyrrolnitrin in shake-flask fermentation. Four cultures were from the multivorans taxon, and the remaining four were members of the fluorescens group. The antifungal agent produced in these strains was isolated and shown to be pyrrolnitrin by comparison with an authentic sample. The strains differed markedly with respect to the amount of pyrrolnitrin produced and in their utilization of exogenous tryptophan. Secondary metabolites, not related to pyrrolnitrin, were also examined and compared with those synthesized in P. aureofaciens. Marked differences were noted in both phenazine pigments and phenolic metabolites. The results of the study suggest that the production of pyrrolnitrin may be widespread in selected taxonomic groups of Pseudomonas. Images Fig. 1 PMID:4968963
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Bondaryk, Małgorzata; Kurzątkowski, Wiesław
2013-01-01
Recent progress in medical sciences and therapy resulted in an increased number of immunocompromised individuals. Candida albicans is the leading opportunistic fungal pathogen causing infections in humans, ranging from superficial mucosal lesions to disseminated or bloodstream candidiasis. Superficial candidiasis not always presents a risk to the life of the infected host, however it significantly lowers the quality of life. Superficial Candida infections are difficult to treat and their frequency of occurrence is currently rising. To implement successful treatment doctors should be up to date with better understanding of C. albicans resistance mechanisms. Despite high frequency of Candida infections there is a limited number of antimycotics available for therapy. This review focuses on current understanding of the mode of action and resistance mechanisms to conventional and emerging antifungal agents for treatment of superficial and mucosal candidiasis. PMID:24353489
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Nam, Hyo-Song; Yang, Hyun-Ju; Oh, Byung Jun; Anderson, Anne J.; Kim, Young Cheol
2016-01-01
Most biocontrol agents for plant diseases have been isolated from sources such as soils and plants. As an alternative source, we examined the feces of tertiary larvae of the herbivorous rhino beetle, Allomyrina dichotoma for presence of biocontrol-active microbes. The initial screen was performed to detect antifungal activity against two common fungal plant pathogens. The strain with strongest antifungal activity was identified as Bacillus amyloliquefaciens KB3. The inhibitory activity of this strain correlated with lipopeptide productions, including iturin A and surfactin. Production of these surfactants in the KB3 isolate varied with the culture phase and growth medium used. In planta biocontrol activities of cell-free culture filtrates of KB3 were similar to those of the commercial biocontrol agent, B. subtilis QST-713. These results support the presence of microbes with the potential to inhibit fungal growth, such as plant pathogens, in diverse ecological niches. PMID:27298603
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Cong, Lin; Lu, Xuelian
2016-01-01
Increasing drug resistance has brought enormous challenges to the management of Trichosporon spp. infections. The in vitro antifungal activities of non-steroidal anti-inflammatory drugs (NSAIDs) against Candida spp. and Cryptococcus spp. were recently discovered. In the present study, the in vitro interactions between three NSAIDs (aspirin, ibuprofen and diclofenac sodium) and commonly used antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) against planktonic and biofilm cells of T. asahii were evaluated using the checkerboard microdilution method. The spectrophotometric method and the XTT reduction assay were used to generate data on biofilm cells. The fractional inhibitory concentration index (FICI) and the ΔE model were compared to interpret drug interactions. Using the FICI, the highest percentages of synergistic effects against planktonic cells (86.67%) and biofilm cells (73.33%) were found for amphotericin B/ibuprofen, and caspofungin/ibuprofen showed appreciable percentages (73.33% for planktonic form and 60.00% for biofilm) as well. We did not observe antagonism. The ΔE model gave consistent results with FICI (86.67%). Our findings suggest that amphotericin B/ibuprofen and caspofungin/ibuprofen combinations have potential effects against T. asahii. Further in vivo and animal studies to investigate associated mechanisms need to be conducted. PMID:27275608
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Al-Wabli, Reem I; Al-Ghamdi, Alwah R; Ghabbour, Hazem A; Al-Agamy, Mohamed H; Monicka, James Clemy; Joe, Issac Hubert; Attia, Mohamed I
2017-02-28
Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was unequivocally determined via the single crystal X-ray technique. The title compound 4 , C 13 H 13 N₃O₃·C₃H₈O, crystallizes in the monoclinic space group P 2₁with a = 9.0963(3) Å, b = 14.7244(6) Å, c = 10.7035(4) Å, β = 94.298 (3)°, V = 1429.57(9) ų, Z = 2. The molecules were packed in the crystal structure by eight intermolecular hydrogen bond interactions. A comprehensive spectral analysis of the title molecule 4 has been performed based on the scaled quantum mechanical (SQM) force field obtained by density-functional theory (DFT) calculations. A molecular docking study illustrated the binding mode of the title compound 4 into its target protein. The preliminary antifungal activity of the title compound 4 was determined using a broth microdilution assay.
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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.
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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.
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Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian
2016-01-01
Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283
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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.
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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.
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Gregorí Valdes, Barbara S; Serro, Ana Paula; Gordo, Paulo M; Silva, Alexandra; Gonçalves, Lídia; Salgado, Ana; Marto, Joana; Baltazar, Diogo; Dos Santos, Rui Galhano; Bordado, João Moura; Ribeiro, Helena Margarida
2017-06-01
Onychomycosis is a fungal nail infection. The development of new topical antifungal agents for the treatment of onychomycosis has focused on formulation enhancements that optimize the pharmacological characteristics required for its effective treatment. Polyurethanes (PUs) have never been used in therapeutic nail lacquers. The aim of this work has been the development of new PU-based nail lacquers with antifungal activity containing 1.0% (wt/wt) of terbinafine hydrochloride. The biocompatibility, wettability, and the prediction of the free volume in the polymeric matrix were assessed using a human keratinocytes cell line, contact angle, and Positron Annihilation Lifetime Spectroscopy determinations, respectively. The morphology of the films obtained was confirmed by scanning electron microscopy, while the nail lacquers' bioadhesion to nails was determined by mechanical tests. Viscosity, in vitro release profiles, and antifungal activity were also assessed. This study demonstrated that PU-terbinafine-based nail lacquers have good keratinocyte compatibility, good wettability properties, and adequate free volume. They formed a homogenous film after application, with suitable adhesion to the nail plate. Furthermore, the antifungal test results demonstrated that the terbinafine released from the nail lacquer Formulation A PU 19 showed activity against dermatophytes, namely Trichophyton rubrum. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
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Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs
Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M. A.; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E.; Casadevall, Arturo
2015-01-01
The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. PMID:26711773
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Moreno, Ana Beatriz; Martínez Del Pozo, Alvaro; San Segundo, Blanca
2006-10-01
The mold Aspergillus giganteus produces a basic, low molecular weight protein showing antifungal properties against economically important plant pathogens, the AFP (Antifungal Protein). In this study, we investigated the mechanisms by which AFP exerts its antifungal activity against Magnaporthe grisea. M. grisea is the causal agent of rice blast, one of the most devastating diseases of cultivated rice worldwide. AFP was purified from the extracellular medium of A. giganteus cultures. The AFP protein was found to induce membrane permeabilization in M. grisea cells. Electron microscopy studies revealed severe cellular degradation and damage of plasma membranes in AFP-treated fungal cells. AFP however failed to induce membrane permeabilization on rice or human HeLa cells. Furthermore, AFP enters the fungal cell and targets to the nucleus, as revealed by co-localization experiments of Alexa-labeled AFP with the SYTOX Green dye. Finally, AFP binds to nucleic acids, including M. grisea DNA. Our results suggest that the combination of fungal cell permeabilization, cell-penetrating ability and nucleic acid-binding activity of AFP determines its potent antifungal activity against M. grisea. These results are discussed in relation to the potential of the AFP protein to enhance crop protection against fungal diseases.
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Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian
2016-04-01
Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. Copyright © 2016 Elsevier Ltd. All rights reserved.
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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
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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.
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[Adequacy of new systemic antifungal agents prescriptions in a teaching hospital].
Pavese, P; Ouachi, Z; Vittoz, J-P; Lebeau, B; Foroni, L; Allenet, B; Stahl, J-P; François, P
2007-12-01
The aim of this study was to evaluate the adequacy and the conformity of prescriptions of new systemic antifungal drugs to guidelines and scientific data. Each prescription of liposomal amphotericin B (lip Amb), voriconazole, and caspofungin made between May 2003 and May 2004 in a teaching hospital were reviewed by an infectious diseases specialist. He used criteria based on marketing authorization, national recommendations, and scientific data. One hundred and fifteen files were studied during the 12-month period and 203 prescriptions analyzed. Most patients were immunodepressed. The indication of the treatment was appropriate for 127 prescriptions (62.6%). Dose and drug interactions were compliant with prescription rules for 158 prescriptions (77.8%). Among the causes of misuse, 16.3% concerned combinations of antifungals. Prescriptions of liposomal amphotericin B, voriconazole and caspofungin complied with guidelines respectively in 69.7, 60.6 and 36.8% of the cases. Among the 127 appropriate prescriptions, the use of cheaper molecules with an equivalent clinical effectiveness would have allowed saving 13.6% of the total cost of these prescriptions. This study will lead us to implement policies for new antifungal prescription.
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Zhang, Ying-lao; Kong, Li-chun; Jiang, Dong-hua; Yin, Cai-ping; Cai, Qi-min; Chen, Qiong; Zheng, Jiang-yan
2011-02-01
Two main phytotoxic and antifungal phthalic acid butyl isobutyl ester (1) and radicinin (2) were isolated from the culture of Curvularia sp. FH01, a fungus residing in the Atractomorpha sinensis gut. The structures of isolated metabolites were established on the basis of spectral analysis. Metabolites 1 and 2 exhibited significant phytotoxic activity against the radical growth of Echinochloa crusgalli with their IC(50) values of 61.9 and 5.9 μg/mL, respectively, which were comparable to that 2,4-dichlorophenoxyacetic acid (2.0 μg/mL) used as a positive control. The antifungal test results showed that compound 2 possessed strong antifungal activity against Magnaporthe grisea (IC(50)=16.3 μg/mL) and Valsa mali (IC(50)=18.2 μg/mL). The findings of the present study suggest that bioactive properties of the fungus FH01 can be attributed to its major components, phthalic acid butyl isobutyl ester and radicinin, and both agents have a potential to be used as herbicide and fungicide. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Krizsán, Krisztina; Tóth, Eszter; Nagy, László G; Galgóczy, László; Manikandan, Palanisamy; Chandrasekaran, Muthusamy; Kadaikunnan, Shine; Alharbi, Naiyf S; Vágvölgyi, Csaba; Papp, Tamás
2015-10-01
A reliable identification method was developed for three closely related Curvularia species, which are frequently isolated from human keratomycoses. Since the traditionally used morphological method and the increasingly used internal transcribed spacer (ITS)-based molecular method proved to be insufficient to discern C. australiensis, C. hawaiiensis and C. spicifera, other molecular targets, such as β-tubulin, translation elongation factor 1-α and the nuclear ribosomal intergenic spacer (IGS), were tested. Among them, the use of the highly divergent IGS sequence is suggested and the species-specific discriminating characters were determined in appropriate reference strains. It was also concluded that C. hawaiiensis and C. spicifera can be predominantly isolated from eye infections among the three species. The in vitro antifungal susceptibility of 10 currently used antifungal agents against 32 Curvularia isolates was also investigated. MICs were determined in each case. Isolates of C. spicifera proved to be less susceptible to the tested antifungals than those of C. hawaiiensis, which underline the importance of the correct identification of these species. © 2015 Blackwell Verlag GmbH.
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Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal Tolerance.
Kim, Jong H; Chan, Kathleen L; Cheng, Luisa W
2017-10-21
Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three cinnamic acid derivatives was investigated against Saccharomyces cerevisiae slt2 Δ, bck1 Δ, mutants of the mitogen-activated protein kinase (MAPK), and MAPK kinase kinase, respectively, in cell wall integrity system, and glr1 Δ, mutant of CAS-responsive glutathione reductase. Cell wall mutants were highly susceptible to four cinnamic acids (4-chloro-α-methyl-, 4-methoxy-, 4-methyl-, 3-methylcinnamic acids), where 4-chloro-α-methyl- and 4-methylcinnamic acids possessed the highest activity. Structure-activity relationship revealed that 4-methylcinnamic acid, the deoxygenated structure of 4-methoxycinnamic acid, overcame tolerance of glr1 Δ to 4-methoxycinnamic acid, indicating the significance of para substitution of methyl moiety for effective fungal control. The potential of compounds as chemosensitizers (intervention catalysts) to cell wall disruptants (viz., 4-chloro-α-methyl- or 4-methylcinnamic acids + CAS or OG) was assessed according to Clinical Laboratory Standards Institute M38-A. Synergistic chemosensitization greatly lowers minimum inhibitory concentrations of the co-administered drug/agents. 4-Chloro-α-methylcinnamic acid further overcame fludioxonil tolerance of Aspergillus fumigatus antioxidant MAPK mutants ( sakA Δ, mpkC Δ). Collectively, 4-chloro-α-methyl- and 4-methylcinnamic acids possess chemosensitizing capability to augment antifungal efficacy of conventional drug/agents, thus could be developed as target-based (i.e., cell wall disruption) intervention catalysts.
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Oral yeast carriage in HIV-infected and non-infected populations in Rosario, Argentina.
Luque, A G; Biasoli, M S; Tosello, M E; Binolfi, A; Lupo, S; Magaró, H M
2009-01-01
The objectives of the present study were: (i) to assess the frequency of oral colonisation by Candida species in HIV-positive patients and to compare it with a population of HIV-negative individuals, (ii) to determine the prevalence of C. dubliniensis in both populations and (iii) to determine the susceptibility of C. dubliniensis and other Candida species isolated from HIV-positive patients to the most commonly used antifungal agents. Oral samples were obtained from 101 HIV-positive and 108 HIV-negative subjects. For yeast identification, we used morphology in cornmeal agar, the API 20C Aux, growth at 45 degrees C, d-xylose assimilation, morphology in sunflower seed agar and PCR. The frequency of isolation of Candida in HIV-positive patients was: C. albicans, 60.7%; C. dubliniensis, 20.2%; C. glabrata, 5.6%; C. krusei, 5.6%; C. tropicalis, 4.5%; others, <5%. The frequency of isolation of Candida in HIV-negative patients was: C. albicans, 73.9%; C. tropicalis, 15.5%; C. dubliniensis, 2.1%; C. glabrata, 2.1%; C. parapsilosis, 2.1%; others, <5%. The oral colonisation by yeast in the HIV-positive patients was higher than that in the HIV-negative subjects. The susceptibilities of 42 Candida isolates to three antifungal agents were determined. All isolates of C. dubliniensis were susceptible to fluconazole, although several individuals had been previously treated with this drug. Out of the 42 Candida isolates, 10 presented resistance to fluconazole and 10 to itraconazole. The presence of Candida species, resistant to commonly used antifungal agents, represents a potential risk in immunocompromised patients.
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Mohammadi, Ali; Hashemi, Maryam; Hosseini, Seyed Masoud
2015-01-01
Background and Objectives: The efficacy of Mentha piperita L, Zataria multiflora Boiss and Thymus vulgaris L essential oils (EOs) was evaluated for controlling the growth of Phytophthora drechsleri, the causative agent of damage to many crops that is consumed directly by humans. Materials and Methods: The EOs used in this study was purchased from Magnolia Co, Iran. The pour plate method in petri dishes containing Potato Dextrose Agar (PDA) was used to evaluate the antifungal properties of EOs. The minimal inhibitory concentrations (MIC), minimum fungicidal concentration (MFC) as well as mycelial growth inhibition (MGI) were measured. The IC50 value (the concentration inhibited 50% of the mycelium growth) was calculated by probit analysis. Results and Conclusion: The fungal growth was significantly reduced by increasing concentrations of tested EOs. The complete reduction was obtained with Shirazi thyme at all concentrations, whereas the complete reduction for peppermint and thyme was observed at 0.4% and 0.8% (v/v) concentrations, respectively. Meanwhile, the minimum inhibition was observed when 0.1% peppermint (MGI values of 9.37%) was used. The IC50, MIC and MFC values of Shirazi thyme was 0.053, 0.1% and 0.2%, respectively. Similarly, MIC and MFC values of peppermint and thyme were recorded 0.4% and 0.8%, respectively. The results obtained from this study may contribute to the development of new antifungal agents to protect the crops from this pathogenic fungus and many agricultural plant pathogens causing drastic crop losses. PMID:26644871
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Aspergillus vertebral osteomyelitis after simultaneous kidney-pancreas transplantation.
Salvalaggio, P R O; Bassetti, M; Lorber, M I; Micheletto, G C; Friedman, A L; Andriole, V T; Basadonna, G P
2003-12-01
Aspergillus osteomyelitis is a rare complication of invasive aspergillosis after organ transplantation. This is the report of a 46-year-old man who underwent a simultaneous pancreas and kidney transplantation, complicated by an Aspergillus osteomyelitis and diskitis of the lumbar spine. Prompt diagnosis with needle biopsy, followed by antifungal therapy using caspofungin, a new antifungal agent recommended for the treatment of refractory aspergillosis, in combination with amphotericin B and an early surgical intervention led to clinical resolution of the infection. Reported cases of spinal aspergillosis after transplantation are reviewed in terms of clinical presentation, risk factors, therapeutic options, and outcome.
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Biofilms and Antifungal Susceptibility Testing.
Simitsopoulou, Maria; Chatzimoschou, Athanasios; Roilides, Emmanuel
2016-01-01
Yeasts and filamentous fungi both exist as single cells and hyphal forms, two morphologies used by most fungal organisms to create a complex multilayered biofilm structure. In this chapter we describe the most widely used assays for the determination of biofilm production and assessment of susceptibility of biofilms to antifungal agents or host phagocytes as various methods, the most frequent of which are staining, confocal laser scanning microscopy, quantification of extracellular DNA and protein associated with extracellular matrix and XTT metabolic reduction assay. Pathway-focused biofilm gene expression profiling is assessed by real-time reverse transcriptase polymerase chain reaction.
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Essential Oils and Antifungal Activity
Coppola, Raffaele; De Feo, Vincenzo
2017-01-01
Since ancient times, folk medicine and agro-food science have benefitted from the use of plant derivatives, such as essential oils, to combat different diseases, as well as to preserve food. In Nature, essential oils play a fundamental role in protecting the plant from biotic and abiotic attacks to which it may be subjected. Many researchers have analyzed in detail the modes of action of essential oils and most of their components. The purpose of this brief review is to describe the properties of essential oils, principally as antifungal agents, and their role in blocking cell communication mechanisms, fungal biofilm formation, and mycotoxin production. PMID:29099084
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A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses.
Mercer, Derry K; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S; O Neil, Deborah A
2013-01-01
Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20-25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones.
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A Prodrug Approach to the Use of Coumarins as Potential Therapeutics for Superficial Mycoses
Mercer, Derry K.; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S.; O′Neil, Deborah A.
2013-01-01
Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20–25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones. PMID:24260474
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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.
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Negri, Clara E; Johnson, Adam; McEntee, Laura; Box, Helen; Whalley, Sarah; Schwartz, Julie A; Ramos-Martín, V; Livermore, Joanne; Kolamunnage-Dona, Ruwanthi; Colombo, Arnaldo L; Hope, William W
2018-01-01
Abstract Background Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Methods The pharmacokinetics (PK) and PD of F901318 were evaluated by developing new in vitro and in vivo models of invasive fungal sinusitis. Galactomannan was used as a pharmacodynamic endpoint in all models. Mathematical PK-PD models were used to describe dose-exposure-response relationships. Results F901318 minimum inhibitory concentrations (MICs) ranged from 0.015 to 0.06 mg/L. F901318 induced a concentration-dependent decline in galactomannan. In the in vitro model, a minimum concentration:MIC of 10 resulted in suppression of galactomannan; however, values of approximately 10 and 9–19 when assessed by survival of mice or the decline in galactomannan, respectively, were equivalent or exceeded the effect induced by posaconazole. There was histological clearance of lung tissue that was consistent with the effects of F901318 on galactomannan. Conclusions F901318 is a potential new agent for the treatment of invasive infections caused by A flavus with PDs that are comparable with other first-line triazole agents. PMID:28968675
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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
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In vitro and in vivo antifungal activities of selected Cameroonian dietary spices.
Dzoyem, Jean Paul; Tchuenguem, Roland T; Kuiate, Jules R; Teke, Gerald N; Kechia, Frederick A; Kuete, Victor
2014-02-17
Spices and herbs have been used in food since ancient times to give taste and flavor and also as food preservatives and disease remedies. In Cameroon, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their antifungal potential.The present work was designed to assess the antifungal properties of extracts from spices used in Cameroonian dietary. The in vitro antifungal activities of twenty three extracts from twenty one spices were assessed by the broth micro-dilution method against eight fungi. Also, the in vivo activity of Olax subscorpioidea extract (the most active extract) was evaluated in rat model of disseminated candidiasis due to Candida albicans by estimating the fungal burden in blood and kidney. Seven extracts (30%) exhibited moderate to significant antifungal activities, inhibiting the growth of the microorganisms at concentrations ranging from 0.048 to 0.39 mg/mL. Olax subscorpioidea extract exhibited the highest antifungal activity particularly against Candida albicans and Candida tropicalis (MIC of 0.097 mg/mL and 0.048 mg/mL respectively). Sixteen extracts (70%) were weakly active (MICs > 6.25 mg/mL). Oral administration of O. subscorpioidea extract at the dose 2 g/kg of body weight (bw) to artificially infected rats revealed a drop in the number of colony forming units per milliliter (cfu/mL) of Candida albicans cells in the blood below the detection limit (100 cfu/mL) while a modest decrease was observed in the kidney. The present work shows that some of the spices studied possess interesting antifungal properties and could be used to treat candidiasis. Among the plant species tested, Olax subscorpioidea displayed the most promising result.
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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.
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De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo
2016-01-01
Background: The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. Objective: The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. Methods: The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. Results: According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a concentration of 10× MIC. The values of the IC50 for the EO were 96.6 μg/mL (HepG-2) and 33.1 μg/mL (MRC-5). Conclusion: As a major virulence mechanism is attributed to these types of infections, the EO is a promising compound to inhibit Candida species, especially considering its action against biofilm. PMID:27517903
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De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; Dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo
2016-08-09
The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a concentration of 10× MIC. The values of the IC50 for the EO were 96.6 μg/mL (HepG-2) and 33.1 μg/mL (MRC-5). As a major virulence mechanism is attributed to these types of infections, the EO is a promising compound to inhibit Candida species, especially considering its action against biofilm.
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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
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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.
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Vella, Antonietta; De Carolis, Elena; Vaccaro, Luisa; Posteraro, Patrizia; Perlin, David S; Kostrzewa, Markus; Posteraro, Brunella; Sanguinetti, Maurizio
2013-09-01
The widespread use of antifungal agents, which is likely to expand with their enhanced availability, has promoted the emergence of drug-resistant strains. Antifungal susceptibility testing (AFST) is now an essential procedure for guiding appropriate antifungal therapy. Recently, we developed a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method that enables the detection of fungal isolates with reduced echinocandin susceptibility, relying on the proteome changes that are detectable after a 15-h exposure of fungal cells to serial drug concentrations. Here, we describe a simplified version of this approach that facilitates discrimination of the susceptible and resistant isolates of Candida albicans after a 3-h incubation in the presence of "breakpoint" level drug concentrations of the echinocandin caspofungin (CSF). Spectra at concentrations of 0 (null), 0.03 (intermediate), and 32 (maximal) μg/ml of CSF were used to create individual composite correlation index (CCI) matrices for 65 C. albicans isolates, including 13 fks1 mutants. Isolates are then classified as susceptible or resistant to CSF if the CCI values of spectra at 0.03 and 32 μg/ml are higher or lower, respectively, than the CCI values of spectra at 0.03 and 0 μg/ml. In this way, the drug resistance of C. albicans isolates to echinocandin antifungals can be quickly assessed. Furthermore, the isolate categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology. The ms-AFST approach may provide a rapid and reliable means of detecting emerging antifungal resistance and accelerating the initiation of appropriate antifungal treatment.
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A Class 1 Histone Deacetylase with Potential as an Antifungal Target.
Bauer, Ingo; Varadarajan, Divyavaradhi; Pidroni, Angelo; Gross, Silke; Vergeiner, Stefan; Faber, Birgit; Hermann, Martin; Tribus, Martin; Brosch, Gerald; Graessle, Stefan
2016-11-01
Histone deacetylases (HDACs) remove acetyl moieties from lysine residues at histone tails and nuclear regulatory proteins and thus significantly impact chromatin remodeling and transcriptional regulation in eukaryotes. In recent years, HDACs of filamentous fungi were found to be decisive regulators of genes involved in pathogenicity and the production of important fungal metabolites such as antibiotics and toxins. Here we present proof that one of these enzymes, the class 1 type HDAC RpdA, is of vital importance for the opportunistic human pathogen Aspergillus fumigatus Recombinant expression of inactivated RpdA shows that loss of catalytic activity is responsible for the lethal phenotype of Aspergillus RpdA null mutants. Furthermore, we demonstrate that a fungus-specific C-terminal region of only a few acidic amino acids is required for both the nuclear localization and catalytic activity of the enzyme in the model organism Aspergillus nidulans Since strains with single or multiple deletions of other classical HDACs revealed no or only moderate growth deficiencies, it is highly probable that the significant delay of germination and the growth defects observed in strains growing under the HDAC inhibitor trichostatin A are caused primarily by inhibition of catalytic RpdA activity. Indeed, even at low nanomolar concentrations of the inhibitor, the catalytic activity of purified RpdA is considerably diminished. Considering these results, RpdA with its fungus-specific motif represents a promising target for novel HDAC inhibitors that, in addition to their increasing impact as anticancer drugs, might gain in importance as antifungals against life-threatening invasive infections, apart from or in combination with classical antifungal therapy regimes. This paper reports on the fungal histone deacetylase RpdA and its importance for the viability of the fungal pathogen Aspergillus fumigatus and other filamentous fungi, a finding that is without precedent in other eukaryotic pathogens. Our data clearly indicate that loss of RpdA activity, as well as depletion of the enzyme in the nucleus, results in lethality of the corresponding Aspergillus mutants. Interestingly, both catalytic activity and proper cellular localization depend on the presence of an acidic motif within the C terminus of RpdA-type enzymes of filamentous fungi that is missing from the homologous proteins of yeasts and higher eukaryotes. The pivotal role, together with the fungus-specific features, turns RpdA into a promising antifungal target of histone deacetylase inhibitors, a class of molecules that is successfully used for the treatment of certain types of cancer. Indeed, some of these inhibitors significantly delay the germination and growth of different filamentous fungi via inhibition of RpdA. Upcoming analyses of clinically approved and novel inhibitors will elucidate their therapeutic potential as new agents for the therapy of invasive fungal infections-an interesting aspect in light of the rising resistance of fungal pathogens to conventional therapies. Copyright © 2016 Bauer et al.
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Graybill, John R.; Bocanegra, Rosie; Najvar, Laura K.; Loebenberg, David; Luther, Mike F.
1998-01-01
Outbred ICR mice were immune suppressed either with hydrocortisone or with 5-fluorouracil and were infected intranasally with Aspergillus fumigatus. Beginning 3 days before infection some groups of mice were given recombinant human granulocyte colony-stimulating factor (G-CSF), SCH56592 (an antifungal triazole), or both. Corticosteroid-pretreated mice responded to SCH56592 and had reduced counts in lung tissue and prolonged survival. In these mice, G-CSF strongly antagonized the antifungal activity of SCH56592. Animals treated with both agents developed large lung abscesses with polymorphonuclear leukocytes and large amounts of Aspergillus. In contrast, mice made neutropenic with 5-fluorouracil and then infected with A. fumigatus conidia benefited from either G-CSF or triazoles, and the effect of the combination was additive rather than antagonistic. Host predisposing factors contribute in different ways to the outcome of growth factor therapy in aspergillosis. PMID:9756743
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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.
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Effect of ferrocene-substituted porphyrin RL-91 on Candida albicans biofilm formation.
Lippert, Rainer; Vojnovic, Sandra; Mitrovic, Aleksandra; Jux, Norbert; Ivanović-Burmazović, Ivana; Vasiljevic, Branka; Stankovic, Nada
2014-08-01
Ferrocene-substituted porphyrin RL-91 exhibits antifungal activity against opportune human pathogen Candida albicans. RL-91 efficiently inhibits growth of both planktonic C. albicans cells and cells within biofilms without photoactivation. The minimal inhibitory concentration for plankton form (PMIC) was established to be 100 μg/mL and the same concentration killed 80% of sessile cells in the mature biofilm (SMIC80). Furthermore PMIC of RL-91 efficiently prevents C. albicans biofilm formation. RL-91 is cytotoxic for human fibroblasts in vitro in concentration of 10 μg/mL, however it does not cause hemolysis in concentrations of up to 50 μg/mL. These findings open possibility for application of RL-91 as an antifungal agent for external antibiofilm treatment of medical devices as well as a scaffold for further development of porphyrin based systemic antifungals. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Samaranayake, Y H; Cheung, B P K; Parahitiyawa, N; Seneviratne, C J; Yau, J Y Y; Yeung, K W S; Samaranayake, L P
2009-02-01
Denture related oral candidiasis is a recalcitrant fungal infection not easily resolved by topical antifungals. The antimycotic protein lysozyme, in saliva is an important host defense mechanism although its activity against Candida biofilms on denture acrylic has not been evaluated. (i) To establish a clinically relevant denture acrylic assay model to develop standardized Candida albicans biofilms, and (ii) assess the inhibitory effects of lysozyme alone and, the latter combined with antifungals (nystatin, amphotericin B, ketoconazole and 5-fluorocytosine) on sessile Candida cells and, finally (iii) to visualize the accompanying ultrastructural changes. The rotating-disc biofilm reactor was used to develop standardized 48 h Candida biofilms on acrylic discs in YNB/100 mM glucose medium and the biofilm metabolic activity was monitored using a tetrazolium reduction assay. The biofilm metabolic activity was similar in 18 identical denture acrylic discs (p<0.05) thus validating the rotating-disc biofilm model. Very low concentrations of lysozyme (6.25 microg/ml) significantly (p<0.01) inhibited Candida biofilm formation indicating that lysozyme may likely regulate intra-oral Candida biofilm development. Although 100 microg/ml lysozyme killed 45% of sessile Candida cells, further increasing its concentration (up to 240 microg/ml) had no such effect. Nystatin, amphotericin B, and ketoconazole in association with 100 microg/ml lysozyme exhibited effective synergistic killing of biofilm Candida in comparison to drug-free controls. Scanning electron and confocal scanning laser microscopy analysis confirmed the latter trends. Our results indicate that agents found in biological fluids such as lysozyme could be a safe adjunct to antifungals in future treatment strategies for recalcitrant candidal infections.
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Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis
2014-01-01
Background Sporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. Sporothrix infections notably occur in outbreaks, with large epidemics currently taking place in southeastern Brazil and northeastern China. Pathogenic species include Sporothrix brasiliensis, Sporothrix schenckii s. str., Sporothrix globosa, and Sporothrix luriei, which exhibit differing geographical distribution, virulence, and resistance to antifungals. The phylogenetically remote species Sporothrix mexicana also shows a mild pathogenic potential. Methods We assessed a genetically diverse panel of 68 strains. Susceptibility profiles of medically important Sporothrix species were evaluated by measuring the MICs and MFCs for amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS). Haplotype networks were constructed to reveal interspecific divergences within clinical Sporothrix species to evaluate genetically deviant isolates. Results ITC and PCZ were moderately effective against S. brasiliensis (MIC90 = 2 and 2 μg/mL, respectively) and S. schenckii (MIC90 = 4 and 2 μg/mL, respectively). PCZ also showed low MICs against the rare species S. mexicana. 5FC, CAS, and FLC showed no antifungal activity against any Sporothrix species. The minimum fungicidal concentration ranged from 2 to >16 μg/mL for AMB against S. brasiliensis and S. schenckii, while the MFC90 was >16 μg/mL for ITC, VRC, and PCZ. Conclusion Sporothrix species in general showed high degrees of resistance against antifungals. Evaluating a genetically diverse panel of strains revealed evidence of multidrug resistant phenotypes, underlining the need for molecular identification of etiologic agents to predict therapeutic outcome. PMID:24755107
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Synthesis and potent in vitro activity of novel 1H-benzimidazoles as anti-MRSA agents.
Karataş, Hacer; Alp, Mehmet; Yildiz, Sulhiye; Göker, Hakan
2012-08-01
A new class of 1H-benzimidazolecarboxamidines was synthesized and evaluated for in vitro antibacterial and antifungal activities, including drug-resistant bacterial strains. The most potent compound (32) has the same ratio of anti-MRSA activity as Vancomycin (minimal inhibitory concentrations value 0.78 μg/mL). The mechanism of action for 1H-benzimidazolecarboxamidine appears to be different from existing antibacterial agents. These compounds have potential for development as a new class of potent anti-MRSA agent. © 2012 John Wiley & Sons A/S.
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Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide
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
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El Shehry, Mohamed F; Ghorab, Mostafa M; Abbas, Samir Y; Fayed, Eman A; Shedid, Said A; Ammar, Yousry A
2018-01-01
In an attempt for development of new antimicrobial agents, three series of quinoline derivatives bearing pyrazole moiety have been synthesized. The first series was synthesized through the synthesis of 4-(quinolin-2-yloxy)benzaldehyde and 4-(quinolin-2-yloxy)acetophenone and then treatment with ketone or aldehyde derivatives to afford the corresponding chalcones. Cyclization of the latter chalcones with hydrazine derivatives led to the formation of new pyrazoline derivatives. The second series was synthesized via the synthesis of 2-hydrazinylquinoline and then treatment with formylpyrazoles to afford the corresponding hydrazonyl pyrazole derivatives. The third series was synthesized through the treatment of 2-hydrazinylquinoline with ethoxyethylidene, dithioacetal and arylidene derivatives to afford the corresponding pyrazole derivatives. The synthesized compounds were evaluated for their expected antibacterial and antifungal activities; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Pyrazole derivative 13b showed better results when compared with the reference drugs as revealed from their MIC values (0.12-0.98 μg/mL). The pyrazole derivative 13b showed fourfold potency of gentamycin in inhibiting the growth of S. flexneri (MIC 0.12 μg/mL). Also, compound 13b showed fourfold potency of amphotericin B in inhibiting the growth of A. clavatus (MIC 0.49 μg/mL) and C. albicans (MIC 0.12 μg/mL), respectively. The same compound showed twofold potency of gentamycin in inhibiting the growth of P. vulgaris (MIC 0.98 μg/mL), equipotent to the ampicillin and amphotericin B in inhibiting the growth of S. epidermidis (MIC 0.49 μg/mL), A. fumigatus (MIC 0.98 μg/mL), respectively. Thus, these studies suggest that quinoline derivatives bearing pyrazole moiety are interesting scaffolds for the development of novel antibacterial and antifungal agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.
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.
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Topical antifungals for seborrhoeic dermatitis
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
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Castanheira, Mariana; Duncanson, Frederick P; Diekema, Daniel J; Guarro, Josep; Jones, Ronald N; Pfaller, Michael A
2012-01-01
Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.
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Duncanson, Frederick P.; Diekema, Daniel J.; Guarro, Josep; Jones, Ronald N.; Pfaller, Michael A.
2012-01-01
Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC90 was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC50 for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC90 for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results. PMID:22083469
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Abbaszadeh, S; Tavakoli, R; Sharifzadeh, A; Shokri, H
2015-12-01
The aim of this study was to assess the potential of lactic acid bacteria (LAB) such as Lactobacillus acidophilus, L. rhamnosus, L. casei, L. paracasei and Bifidobacterium bifidum to inhibit the outgrowth of some common food-spoiling fungi including Aspergillus niger, A. flavus, A. parasiticus and Penicillium chrysogenum. Bacterial isolates were cultured on Mann Rogosa Sharpe (MRS) broth and liquid cultures and supernatants were prepared. The antifungal activity was tested using the agar well diffusion method. Both liquid culture and supernatant of L. casei isolate exhibited high antifungal activity, followed by L. acidophilus and L. paracasei isolates. The least activity was recorded for the isolates B. bifidum, while the isolate L. rhamnosus was moderately active against tested fungi. The antifungal activity of the supernatants obtained from all probiotic isolates against fungi was significantly less than that of liquid cultures (P<0.05). Antifungal activity evaluation showed that A. flavus was the most inhibited fungus by probiotic bacteria, followed by P. chrysogenum, A. niger and A. parasiticus. These results suggest that probiotic bacteria strains have the ability to prevent the growth of pathogenic and mycotoxigenic fungi as antifungal agents for various biomedical applications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Evaluation of 1,3-benzoxathiol-2-one Derivatives as Potential Antifungal Agents.
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.
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Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.
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.
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Essential oil of Algerian Eucalyptus citriodora: Chemical composition, antifungal activity.
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.
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Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs.
Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M A; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E; Casadevall, Arturo; Gonçalves, Teresa
2015-12-28
The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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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.
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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.
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In vitro antifungal susceptibility of Trichophyton violaceum isolated from tinea capitis patients.
Deng, S; de Hoog, G S; Verweij, P E; Zoll, J; Ilkit, M; Morsali, F; Abliz, P; Wang, X; Zhan, P; Yang, L; Hasimu, H; Liao, W; Pan, W; Seyedmousavi, S
2015-04-01
Trichophyton violaceum is an anthropophilic dermatophyte that is endemic to parts of Africa and Asia and is sporadic in Europe. T. violaceum mainly causes tinea capitis in both children and adolescents. Although the infections caused by T. violaceum are of considerable medical importance, its antifungal susceptibility profile remains poorly examined. In this study, we tested the in vitro antifungal susceptibility of a set of clinical T. violaceum isolates obtained from tinea capitis patients, using the CLSI broth microdilution method. We tested eight antifungals and used isolates collected from Western China (21), Eastern China (12), the Middle East (1), Europe (20), South Africa (7) and Canada (1). The geometric means of the MICs of the antifungals for all isolates were as follows (in increasing order): posaconazole, 0.021 mg/L; terbinafine, 0.023 mg/L; voriconazole, 0.062 mg/L; amphotericin B, 0.20 mg/L; itraconazole, 0.34 mg/L; caspofungin, 0.56 mg/L; fluconazole, 4.23 mg/L; and flucytosine, 8.46 mg/L. No statistically significant differences in the susceptibility profiles of T. violaceum were detected within the geographical regions tested. Posaconazole, terbinafine and voriconazole were shown to be the most potent antifungal agents against T. violaceum isolates obtained from tinea capitis patients worldwide. These results might help clinicians in developing appropriate therapies that have a high probability of successfully treating tinea capitis due to T. violaceum. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Lopes, Marcos Roberto; Klein, Mariana Nadjara; Ferraz, Luriany Pompeo; da Silva, Aline Caroline; Kupper, Katia Cristina
2015-06-01
In this study, we evaluated the efficiency of six isolates of Saccharomyces cerevisiae in controlling Colletotrichum acutatum, the causal agent of postbloom fruit drop that occur in pre-harvest citrus. We analyzed the mechanisms of action involved in biological control such as: production of antifungal compounds, nutrient competition, detection of killer activity, and production of hydrolytic enzymes of the isolates of S. cerevisiae on C. acutatum and their efficiency in controlling postbloom fruit drop on detached citrus flowers. Our results showed that all six S. cerevisiae isolates produced antifungal compounds, competed for nutrients, inhibited pathogen germination, and produced killer activity and hydrolytic enzymes when in contact with the fungus wall. The isolates were able to control the disease when detached flowers were artificially inoculated, both preventively and curatively. In this work we identified a novel potential biological control agent for C. acutatum during pre-harvest. This is the first report of yeast efficiency for the biocontrol of postbloom fruit drop, which represents an important contribution to the field of biocontrol of diseases affecting citrus populations worldwide. Copyright © 2015 Elsevier GmbH. All rights reserved.
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Badali, Hamid; Fakhim, Hamed; Zarei, Fereshteh; Nabili, Mojtaba; Vaezi, Afsane; Poorzad, Nafiseh; Dolatabadi, Somayeh; Mirhendi, Hossein
2016-04-01
Black aspergilli, particularly Aspergillus niger and A. tubingensis, are the most common etiological agents of otomycosis followed by onychomycosis, pulmonary aspergillosis and aspergilloma. However, so far there is no systematic study on their antifungal susceptibility profiles. A collection of 124 clinical and environmental species of black aspergilli consisted of A. niger, A. tubingensis, A. uvarum. A. acidus and A. sydowii were verified by DNA sequencing of the partial β-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MECs of caspofungin were performed based on CLSI M38-A2. Posaconazole and caspofungin had the lowest MIC range (0.016-0.125 µg/ml and 0.008-0.031 µg/ml, respectively), followed by amphotericin B (0.25-4 µg/ml), voriconazole (0.125-16 µg/ml) and itraconazole (0.25 to >16) in an increasing order. Some strains of A. niger showed high MIC value for itraconazole and voriconazole (>16 µg/ml), in contrast only environmental isolates of A. tubingensis had high itraconazole MICs (>16 µg/ml). These results confirm that posaconazole and caspofungin are potential drugs for treatment of aspergillosis due to opportunistic agents of Aspergillus Nigri complex. However, in vivo efficacy remains to be determined.
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Antimicrobial activity of pomegranate peel extracts as affected by cultivar.
Rosas-Burgos, Ema C; Burgos-Hernández, Armando; Noguera-Artiaga, Luis; Kačániová, Miroslava; Hernández-García, Francisca; Cárdenas-López, José L; Carbonell-Barrachina, Ángel A
2017-02-01
Some studies have reported that different parts of the pomegranate fruit, especially the peel, may act as potential antimicrobial agents and thus might be proposed as a safe natural alternative to synthetic antimicrobial agents. The high tannin content, especially punicalagin, found in pomegranate extracts, has been reported as the main compound responsible for such antimicrobial activity. Because the pomegranate peel chemical composition may vary with the type of cultivar (sweet, sour-sweet and sour), pomegranates may also differ with respect to their antimicrobial capacity. The extract from PTO8 pomegranate cultivar peel had the highest antimicrobial activity, as well as the highest punicalagins (α and β) and ellagic acid concentrations. In the results obtained from both antibacterial and antifungal activity studies, the sour-sweet pomegranate cultivar PTO8 showed the best antimicrobial activity, and the highest ellagic acid concentrations. The results of the present study suggest that ellagic acid content has a significant influence on the antimicrobial activity of the pomegranate extracts investigated. The pomegranate peel of the PTO8 cultivar is a good source of antifungal and antibacterial compounds, and may represent an alternative to antimicrobial agents of synthetic origin. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
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Khosravi, A R; Sharifzadeh, A; Nikaein, D; Almaie, Z; Gandomi Nasrabadi, H
2018-06-01
Systemic candidiasis has become an emerging fungal infection in recent years. Anti-Candida resistance to conventional antifungal agents has subsequently increased. This study reported the chemical composition, antioxidant and anti-Candida activity of Origanum majorana, Artemisia dracunculus, Cymbopogon citrate, Cinnamomum verum and Caryophyllus aromaticus essential oils. Different Candida species, from urine tracts of hospitalized patients, were included to be challenged with understudied essential oils. Chemical compositions were determined using gas chromatography/mass spectroscopy (GC/MS) analysis and antioxidant activity was measured using DDPH assay. MIC of these essential oils was evaluated using broth micro-dilution test. Caryophyllus aromaticus had the highest antioxidant activity while the lowest antioxidant activity was for Artemisia dracunculus. MICs of Cinnamomum verum, Caryophillium aromaticus, Artemisia dracunculus, Origanum vulgare and Cymbopogon citratus essential oils ranged from 125 to 175μg/mL (mean value: 147.7±25.5μg/mL), 700 to 1000μg/mL (mean value: 740.9±105.4μg/mL), 1000 to 2000μg/mL (mean value: 1454.5±509.6μg/mL), 173 to 350μg/mL (mean value: 208±55.8μg/mL) and 125 to 175μg/mL (mean value: 156.8±24.6μg/mL) for different Candida species, respectively. In general, natural compounds are suitable to be used as anti-Candida and antioxidant agents. However in this stage, these compounds could be applied as supplementary agents along with conventional antifungal drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Neppelenbroek, Karin Hermana; Lima, Jozely Francisca Mello; Hotta, Juliana; Galitesi, Lucas Lulo; Almeida, Ana Lucia Pompéia Fraga; Urban, Vanessa Migliorini
2018-02-01
To investigate the ultimate tensile strength of temporary soft denture liners modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm (SC5314) determined in previous microbiological research. Dumbbell-shaped specimens (n = 7) with a central cross-sectional area of 6 × 3 × 33 mm were produced by Softone and Trusoft, without (control) or with incorporation of drugs in powder form at MICs for C. albicans biofilm (per g of material powder): nystatin (0.032 g), chlorhexidine diacetate (0.064 g), ketoconazole (0.128 g), miconazole (0.256 g), and itraconazole (0.256 g). After plasticization, specimens were immersed in distilled water at 37°C for 24 hours, 7 or 14 days, and then tested in tension in a universal testing machine at 40 mm/min. Data of tensile strength (MPa) and elongation percentage (%) were submitted to 3-way ANOVA and Tukey's test (α = 0.05). At the end of 14 days, the tensile strength for both materials was significantly lower in the groups modified by miconazole and itraconazole compared to the other groups (p < 0.0001), which showed no significant difference between them (p > 0.05). After 7 and 14 days in water, miconazole and itraconazole added into both materials resulted in significantly lower elongation percentages compared to the other antifungal agents and control (p < 0.0001), which were similar to each other (p > 0.05). The addition of the nystatin, chlorhexidine, and ketoconazole at MICs for C. albicans biofilm resulted in no harmful effects on the tensile strength and elongation percentage of the temporary soft denture liner materials up to 14 days. © 2017 by the American College of Prosthodontists.
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Zarei Mahmoudabadi, Ali; Rezaei-Matehkolaei, Ali; Navid, Mojgan; Torabizadeh, Mehdi; Mazdarani, Shahnam
2015-07-01
Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis. The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals. In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida . Morphology on cornmeal agar, germ tube formation and growth at 45°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method. In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of ≤8 μg/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at ≥8 μg/mL. This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards.
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Zarei Mahmoudabadi, Ali; Rezaei-Matehkolaei, Ali; Navid, Mojgan; Torabizadeh, Mehdi; Mazdarani, Shahnam
2015-01-01
Background: Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis. Objectives: The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals. Materials and Methods: In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida . Morphology on cornmeal agar, germ tube formation and growth at 45°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method. Results: In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of ≤8 μg/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at ≥8 μg/mL. Conclusions: This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards. PMID:26312235
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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.
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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
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Mello, Enrica; Posteraro, Brunella; Vella, Antonietta; De Carolis, Elena; Torelli, Riccardo; D'Inzeo, Tiziana; Verweij, Paul E; Sanguinetti, Maurizio
2017-06-01
We tested 59 common and 27 uncommon Aspergillus species isolates for susceptibility to the mold-active azole antifungal agents itraconazole, voriconazole, and posaconazole using the Sensititre method. The overall essential agreement with the CLSI reference method was 96.5% for itraconazole and posaconazole and was 100% for voriconazole. By the Sensititre method as well as the CLSI reference method, all of 10 A. fumigatus isolates with a cyp51 mutant genotype were classified as being non-wild-type isolates (MIC > epidemiological cutoff value [ECV]) with respect to triazole susceptibility. Copyright © 2017 American Society for Microbiology.
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Mello, Enrica; Posteraro, Brunella; Vella, Antonietta; De Carolis, Elena; Torelli, Riccardo; D'Inzeo, Tiziana; Verweij, Paul E.
2017-01-01
ABSTRACT We tested 59 common and 27 uncommon Aspergillus species isolates for susceptibility to the mold-active azole antifungal agents itraconazole, voriconazole, and posaconazole using the Sensititre method. The overall essential agreement with the CLSI reference method was 96.5% for itraconazole and posaconazole and was 100% for voriconazole. By the Sensititre method as well as the CLSI reference method, all of 10 A. fumigatus isolates with a cyp51 mutant genotype were classified as being non-wild-type isolates (MIC > epidemiological cutoff value [ECV]) with respect to triazole susceptibility. PMID:28416538
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Functional expression and characterization of CYP51 from dandruff-causing Malassezia globosa.
Kim, Donghak; Lim, Young-Ran; Ohk, Seul Ong; Kim, Beom Joon; Chun, Young-Jin
2011-02-01
Malassezia globosa is one of the most common yeasts to cause various human skin diseases including dandruff and seborrheic dermatitis. Genomic analysis of M. globosa revealed four putative cytochrome P450 (CYP) enzymes. Here, we report the purification and characterization of recombinant CYP51, a putative lanosterol 14α-demethylase, from M. globosa. The M. globosa CYP51 was expressed heterologously in Escherichia coli, followed by purification. Purified CYP51 showed a typical reduced CO-difference spectrum of P450, with a maximum absorption at 447 nm. Purified CYP51 exhibited tight binding to azole antifungal agents such as ketoconazole, econazole, fluconazole, or itraconazole, with K(d) values around 0.26-0.84 μM, which suggests that CYP51 is an orthologous target for antifungal agents in the M. globosa. In addition, three mutations (Y127F, A169S, and K176N) in the amino acid sequence of M. globosa CYP51 were identified in one of the azole-resistant strains. Homology modeling of M. globosa CYP51 suggested that the Y127F mutation may influence the resistance to azoles by blocking substrate access channels. Taken together, functional expression and characterization of the CYP51 enzyme can provide a fundamental basis for a specific antifungal drug design for dandruff caused by M. globosa. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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2018-01-01
Background Green synthesis is an ecological technique for the production of well characterized metallic nanoparticles using plants. This study investigated the synthesis of silver nanoparticles (AgNPs) using a Caesalpinia ferrea seed extract as a reducing agent. Methods The formation of AgNPs was identified by instrumental analysis, including ultraviolet–visible (UV–Vis) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) of the AgNPs, and surface-enhanced Raman scattering (SERS) spectra of rhodamine-6G (R6G). We studied the physicochemical characterization of AgNPs, evaluated them as an antifungal agent against Candida albicans, Candida kruzei, Candida glabrata and Candida guilliermondii, and estimated their minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. Lastly, this study evaluated the cytotoxicity of the AgNPs in murine L929 fibroblasts cells using an MTT assay. Results The UV–Vis spectroscopy, SERS, SEM and XRD results confirmed the rapid formation of spheroidal 30–50 nm AgNPs. The MIC and MFC values indicated the antifungal potential of AgNPs against most of the fungi studied and high cell viability in murine L929 fibroblasts. In addition, this study demonstrated that C. ferrea seed extracts may be used for the green synthesis of AgNPs at room temperature for the treatment of candidiasis. PMID:29576936
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[Tinea in the genital area : A diagnostic and therapeutic challenge].
Ginter-Hanselmayer, G; Nenoff, P; Kurrat, W; Propst, E; Durrant-Finn, U; Uhrlaß, S; Weger, W
2016-09-01
Pubogenital tinea or tinea genitalis represents a rare type of dermatophytosis which, however, is increasingly being diagnosed. The mons pubis is affected, but also the outer regions to the penis shaft and the labia together with the groins. Pubogenital tinea is a more superficial erythrosquamous type, but strong inflammatory dermatomycoses of the genital area as tinea genitalis profunda ranging to kerion celsi are observed. A total of 30 patients (14-63 years of age, 11 men and 19 women) with pubogenital tinea are described. Most patients originated from Graz, Austria, while 2 patients were from Germany (Saxony and Isle of Sylt). Causative agents were mainly zoophilic dermatophytes: Microsporum (M.) canis (11), Trichophyton (T.) interdigitale (9), T. anamorph of Arthroderma benhamiae (2), and T. verrucosum (1). Anthropophilic fungi were T. rubrum (6) and T. tonsurans (1). Anamnestic questions should include contact with pets, physical activities, and travel. Genital shaving and concurrent tinea pedis and onychomycosis are disposing factors. Treatment consisted of oral antifungals except in the three women who were pregnant. Preferably, itraconazole or terbinafine was used, while in a single case, fluconazole was administered. Griseofulvin was not used, because this classic systemic antifungal agent is not allowed any more in Austria. In one patient, oral antifungal therapy was changed from itraconazole to terbinafine due to inefficacy.
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Experimental and Conformational Analyses of Interactions between Butenafine and Lipids
Mingeot-Leclercq, Marie-Paule; Gallet, Xavier; Flore, Christel; Van Bambeke, Françoise; Peuvot, Jacques; Brasseur, Robert
2001-01-01
Butenafine (N-4-tert-butylbenzyl-N-methyl-1-naphtalenemethylamine hydrochloride) is an antifungal agent of the benzylamine class that has excellent therapeutic efficacy and a remarkably long duration of action when applied topically to treat various mycoses. Given the lipophilic nature of the molecule, efficacy may be related to an interaction with cell membrane phospholipids and permeabilization of the fungal cell wall. Similarly, high lipophilicity could account for the long duration of action, since fixation to lipids in cutaneous tissues might allow them to act as local depots for slow release of the drug. We have therefore used computer-assisted conformational analysis to investigate the interaction of butenafine with lipids and extended these observations with experimental studies in vitro using liposomes. Conformational analysis of mixed monolayers of phospholipids with the neutral and protonated forms of butenafine highlighted a possible interaction with both the hydrophilic and hydrophobic domains of membrane phospholipids. Studies using liposomes demonstrated that butenafine increases membrane fluidity [assessed by fluorescence polarization of 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenylhexatriene] and membrane permeability (studied by release of calcein from liposomes). The results show, therefore, that butenafine readily interacts with lipids and is incorporated into membrane phospholipids. These findings may help explain the excellent antifungal efficacy and long duration of action of this drug when it is used as a topical antifungal agent in humans. PMID:11709307
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Species spectrum and antifungal susceptibility profile of vaginal isolates of Candida in Kuwait.
Alfouzan, W; Dhar, R; Ashkanani, H; Gupta, M; Rachel, C; Khan, Z U
2015-03-01
The study was undertaken to determine the prevalence of vulvovaginal candidiasis (VVC) among patients with vaginitis, frequency of different Candida species, and their susceptibility profile. Over six months period, high vaginal swabs were cultured on Sabouraud's dextrose agar and isolates were identified by culture on CHROMagar Candida and Vitek2 yeast identification system or/and API 20C (BioMerieux, France). Antifungal susceptibility of the Candida isolates was determined by E-test against amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole and caspofungin. One thousand seven hundred and fifty-two women with vaginitis were screened for the prevalence of Candida spp. Vaginal swab cultures of 231 (13.2%) women yielded Candida spp. The isolation rates of different species were as follows: Candida albicans (73.9%), Candida glabrata (19.8%), Candida kefir (1.94%), Candida tropicalis (0.96%), Candida parapsilosis (0.96%), Candida krusei (0.96%), Candida guilliermondii (0.96%), and Saccharomyces cerevisiae (0.52%). All strains of C. albicans and non-C. albicans were susceptible to most of the antifungal agents tested. The high frequency with which C. albicans was recovered and its azole susceptibility support the continued use of azole agents for empirical therapy of uncomplicated VVC. However, a larger controlled study is required to determine the role of non-C. albicans in recurrent VVC. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
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Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.
Vargas-Muñiz, José M; Renshaw, Hilary; Waitt, Greg; Soderblom, Erik J; Moseley, M Arthur; Palmer, Jonathan M; Juvvadi, Praveen R; Keller, Nancy P; Steinbach, William J
2017-04-01
Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal. Copyright © 2017 Elsevier Inc. All rights reserved.
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Phytochemicals as Inhibitors of Candida Biofilm.
Raut, Jayant Shankar; Karuppayil, Sankunny Mohan
2016-01-01
Candida biofilm and associated infections is a serious threat to the large population of immunocompromised patients. Biofilm growth on prosthetic devices or host tissue shows reduced sensitivity to antifungal agents and persists as a reservoir of infective cells. Options for successful treatment of biofilm associated Candida infections are restricted because most of the available antifungal drugs fail to eradicate biofilms. Various plant actives are known to possess interesting antifungal properties. To explore and review the potential of phytochemicals as a novel strategy against Candida biofilms is the intent of present article. Thorough literature search is performed to identify Candida biofilm inhibitors of plant origin. An account of efficacy of selected phytochemicals is presented taking into consideration their biofilm inhibitory concentrations. This review discusses biofilm formation by Candida species, their involvement in human infections, and associated drug resistance. It gives insight into the biofilm inhibitory potential of various phytochemicals. Based on the available reports including the work done in our laboratory, several plant extracts, essential oils and phytomolecules have been identified as excellent inhibitors of biofilms of C. albicans and non-albicans Candida species (NACS). Selected phytochemicals which exhibit activities at low concentrations without displaying toxicity to host are potential therapeutic agents against biofilm associated Candida infections. In vivo testing in animal models and clinical trials in humans are required to be taken up seriously to propose few of the phytochemicals as candidate drug molecules.
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In vitro inhibitory activities of magnolol against Candida spp.
Zhou, Peiru; Fu, Jingya; Hua, Hong; Liu, Xiaosong
2017-01-01
Candida spp. cause various infections involving the skin, mucosa, deep tissues, and even life-threatening candidemia. They are regarded as an important pathogen of nosocomial bloodstream infection, with a high mortality rate. As a result of prolonged exposure to azoles, the therapeutic failure associated with azoles resistance has become a serious challenge in clinical situations. Therefore, novel, alternative antifungals are required urgently. In the present study, the CLSI M-27A broth microdilution method and the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay were used to evaluate the antifungal effects of magnolol against various standard Candida strains in planktonic mode and biofilm formation, respectively. The antifungal activity of magnolol was demonstrated in planktonic C. albicans and non-albicans Candida species, especially fluconazole-resistant Candida krusei , with the minimum inhibitory concentrations ranging from 10 to 40 μg/mL. The BMIC 90 (minimum concentration with 90% Candida biofilm inhibited) values of magnolol ranged from 20 to 160 μg/mL, whereas the BMIC 90 values of fluconazole were more than 128 μg/mL. As an alternative and broad-spectrum antifungal agent, magnolol might be of benefit to the treatment of refractory Candida infection.
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Antifungal activity of Cymbopogon winterianus jowitt ex bor against Candida albicans
de Oliveira, Wylly Araújo; de Oliveira Pereira, Fillipe; de Luna, Giliara Carol Diniz Gomes; Lima, Igara Oliveira; Wanderley, Paulo Alves; de Lima, Rita Baltazar; de Oliveira Lima, Edeltrudes
2011-01-01
Candida albicans is an opportunistic yeast and a member of the normal human flora that commonly causes infections in patients with any type of deficiency of the immune system. The essential oils have been tested for antimycotic activity and pose much potential as antifungal agents. This work investigated the activity of the essential oil of Cymbopogon winterianus against C. albicans by MIC, MFC and time-kill methods. The essential oil (EO) was obtained by hydrodistillation using a Clevenger-type apparatus. It was tested fifteen strains of C. albicans. The MIC was determined by the microdilution method and the MFC was determined when an aliquot of the broth microdilution was cultivated in SDA medium. The phytochemical analysis of EO showed presence of citronellal (23,59%), geraniol (18,81%) and citronellol (11,74%). The EO showed antifungal activity, and the concentrations 625 µg/mL and 1250 µg/mL inhibited the growth of all strains tested and it was fungicidal, respectively. The antimicrobial activity of various concentrations of EO was analyzed over time, it was found concentration-dependent antifungal activity, whose behavior was similar to amphotericin B and nystatin. PMID:24031651
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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
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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.
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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.
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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.
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Antifungal properties of essential oils for improvement of indoor air quality: a review.
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.
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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.
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Proteomics of drug resistance in Candida glabrata biofilms.
Seneviratne, C Jayampath; Wang, Yu; Jin, Lijian; Abiko, Y; Samaranayake, Lakshman P
2010-04-01
Candida glabrata is a fungal pathogen that causes a variety of mucosal and systemic infections among compromised patient populations with higher mortality rates. Previous studies have shown that biofilm mode of the growth of the fungus is highly resistant to antifungal agents compared with the free-floating or planktonic mode of growth. Therefore, in the present study, we used 2-D DIGE to evaluate the differential proteomic profiles of C. glabrata under planktonic and biofilm modes of growth. Candida glabrata biofilms were developed on polystyrene surfaces and age-matched planktonic cultures were obtained in parallel. Initially, biofilm architecture, viability, and antifungal susceptibility were evaluated. Differentially expressed proteins more than 1.5-fold in DIGE analysis were subjected to MS/MS. The transcriptomic regulation of these biomarkers was evaluated by quantitative real-time PCR. Candida glabrata biofilms were highly resistant to the antifungals and biocides compared with the planktonic mode of growth. Candida glabrata biofilm proteome when compared with its planktonic proteome showed upregulation of stress response proteins, while glycolysis enzymes were downregulated. Similar trend could be observed at transcriptomic level. In conclusion, C. glabrata biofilms possess higher amount of stress response proteins, which may potentially contribute to the higher antifungal resistance seen in C. glabrata biofilms.
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Fungous and Bacterial Skin Infections in the Tropics.
1975-01-01
reactions. A new topical antifungal agent, Clotrimazole, was shown to be effective against Tinea Corporis, Tinea Cruris and Tinea Pedis . Control of...was effective in the treatment of Tinea Cruris and Candidiasis, but the Thimerosol preservative in the cream was responsible for several allergic skin
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76 FR 16297 - Aspergillus flavus
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-23
... commodities, when applied/used as an antifungal agent. The Arizona Cotton Research and Protection Council... petition (PP 9E7662) by the Arizona Cotton Research and Protection Council, 3721 East Wier Ave., Phoenix... Cotton Research and Protection Council, which is available in the docket, http://www.regulations.gov...
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Sertaconazole nitrate cream 2% for the treatment of tinea pedis.
Ribotsky, Bret M
2009-05-01
Tinea pedis, both in its acute and chronic phase, is a common skin condition that often is overlooked but can lead to onychomycosis and acute bacterial cellulitis if left untreated. Therefore, aggressive treatment with a topical antifungal agent is warranted. Sertaconazole nitrate cream 2% is a newer imidazole agent that possesses both fungicidal and fungistatic properties to eradicate existing infections. In addition to antifungal properties, it exhibits anti-inflammatory and antipruritic effects. Controlled clinical trials have confirmed its safety, tolerability, and efficacy in participants with tinea pedis. We report 2 patients with chronic tinea pedis of many years' duration and demonstrate the usefulness of sertaconazole nitrate cream 2% in the clinical setting. Tinea pedis was confirmed by results of a potassium hydroxide preparation. Both patients experienced marked improvement by the second week of twice-daily treatment with sertaconazole nitrate cream 2%. Clinical cure was achieved in both patients. These findings suggest that sertaconazole nitrate cream 2% is an effective option for the treatment of tinea pedis.
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Past, Recent Progresses and Future Perspectives of Nanotechnology Applied to Antifungal Agents.
Roque, Luis; Molpeceres, Jesus; Reis, Claudia; Rijo, Patrícia; Reis, Catarina Pinto
2017-01-01
Candida species remain a significant cause of nosocomial bloodstream infections, associated with prolonged hospital stay in the ICU and high healthcare cost. The incidence of Candida is very high in certain risk groups of patients (AIDS, diabetes, cancer, etc.). Recent developments of nanotechnology have strongly contributed to the design of new multifunctional drug carriers that improve drug bioavailability through a controlled and prolonged release profile or even through a more specific targeted delivery of the antifungal agent. Those types of systems have strongly increased with a progressive generation of new structures, permitting the conjunction of new materials, biomolecules, physical and chemical techniques, for better outcomes. Nanotechnology shows expanded possibilities within the medical field and in the case of the yeast infections it may overcome several issues related with the fungal proliferation or higher inhibition of the pathogen causing the infection. This review covers a period of the most representative research of Candidiasis since 1993 to the present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Mondal, Prithusayak; Kumar, Rajesh; Gogoi, Robin
2017-02-01
Fungal diseases posing a severe threat to the production of pulses, a major protein source, necessitates the need of new highly efficient antifungal agents. The present study was aimed to develop azomethine based nano-fungicides for protecting the crop from fungal pathogens and subsequent yield losses. The protocol for the formation of nano-azomethines was generated and standardized. Technically pure azomethines were transformed into their nano-forms exploiting polyethylene glycol as the surface stabilizer. Characterization was performed by optical (imaging) probe (Zetasizer) and electron probe (TEM) characterization techniques. The mean particle sizes of all nano-fungicides were below 100nm. In vitro fungicidal potential of nano-chemicals was increased by 2 times in comparison to that of conventional sized azomethines against pathogenic fungi, namely, Rhizoctonia solani, Rhizoctonia bataticola and Sclerotium rolfsii. The performance of nano-chemicals in pot experiment study was also superior to conventional ones as antifungal agent. Copyright © 2016 Elsevier Inc. All rights reserved.
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Odio, C M
2010-04-01
Fungal nosocomial infections have gradually and consistently increased since the 90s.This increasing threat is closely related with the growing number of people with immune system disorders and their survival. It is also related with the destruction of their physical barriers against infection due to the use of cytotoxic drugs or invasive procedures, such is the case of cancer patients and bone marrow and solid organ transplant patients. Increased survival of patients with congenital or acquired immunodeficiency, premature babies and patients with complex congenital malformations, especially in the gastrointestinal tract, also add up to this scenario. The occurrence of yeast and filamentous fungi infections, especially of the Candida species, has been on the rise. Azole agents overuse, especially fluconazole, for the treatment and prophylaxis of fungal infections has put selective pressure on Candida spp. which resulted in an increase of non-albican species such as C. krusei, C. glabrata and C. famata, among others, as well as their growing resistance to these antifungal agents.
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Moghadam, Mahboube Eslami; Divsalar, Adeleh; Zare, Marziye Shahraki; Gholizadeh, Roghayeh; Mahalleh, Doran; Saghatforosh, Lotfali; Sanati, Soheila
2017-11-02
Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The structures of the compounds were determined by UV-visible and FT-IR spectroscopic methods and elemental analysis. The biological activities of Ni and Cu complexes, as anticancer agents, were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The MTT studies showed Cc 50 values are 21 and 160 µM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex has Cc 50 almost seven times of that obtained for cisplatin. Biological activity of the Ni(II) and Cu(II) complexes were also assayed against selective microorganisms by disc diffusion method. These results showed that the Cu(II) complex is antifungal agent but Ni(II) complex has antibacterial activity.
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NASA Astrophysics Data System (ADS)
Karakurt, Tuncay; Cukurovali, Alaaddin; Subasi, Nuriye Tuna; Onaran, Abdurrahman; Ece, Abdulilah; Eker, Sıtkı; Kani, Ibrahim
2018-02-01
In the present study, a single crystal of a Schiff base, 2,2‧(hydrazine-1,2-diylidenebis(propan-1-yl-1-ylidene))diphenol, was synthesized. The structure of the synthesized crystal was confirmed by 1H and 13C NMR spectroscopic and X-ray diffraction analysis techniques. Experimental and theoretical studies were carried out on two tautomeric structures. It has been observed that the title compound studied can be in two different tautomeric forms, phenol-imine and keto-amine. Theoretical calculations have been performed to support experimental results. Accordingly, the geometric parameters of the compound were optimized by the density functional theory (DFT) method using the Gaussian 09 and Quantum Espresso (QE) packet program was used for periodic boundary conditions (PBC) studies. Furthermore, the compound was also tested for in vitro antifungal activity against Sclerotinia sclerotiorum, Alternaria solani, Fusarium oxysporum f. sp. lycopersici and Monilinia fructigena plant pathogens. Promising inhibition profiles were observed especially towards A. solani. Finally, molecular docking studies and post-docking procedure based on Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) were also carried out to get insight into the compound's binding interactions with the potential. Although theoretical calculations showed that the phenol-imine form was more stable, keto-amine form was predicted to have better binding affinity which was concluded to result from loss of rotational entropy in phenol-imine upon binding. The results obtained here from both experimental and computational methods might serve as a potential lead in the development of novel anti-fungal agents.