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Sample records for antifungals myclobutanil propiconazole

  1. COMPARATIVE LIVER P450 ENZYME ACTIVITY AND HISTOPATHOLOGY IN MICE TREATED WITH THE CONAZOLE FUNGICIDES: MYCLOBUTANIL, PROPICONAZOLE AND TRIADIMETON

    EPA Science Inventory

    Conazoles used in agriculture and pharmaceutical products comprise a class of chemicals which inhibit ergosterol biosynthesis to act as fungicides. Both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen....

  2. TRANSCRIPTIONAL PROFILES IN LIVER FROM RATS TREATED WITH TUMORIGENIC AND NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on t...

  3. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  4. TOXICITY PROFILES IN RATS TREATED WITH TUMORIGENIC AND NONTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepa...

  5. Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

    EPA Science Inventory

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

  6. TOXICITY PROFILES IN MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles comprise a class of fungicides used in agriculture and as pharmaceutical products. The fungicidal properties of conazoles are due to their inhibition of ergosterol biosynthesis. Certain conazoles are tumorigenic in rodents; both propiconazole and triadimefon are hepatot...

  7. Propiconazole

    Integrated Risk Information System (IRIS)

    Propiconazole ; CASRN 60207 - 90 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  8. Development of a difenoconazole/propiconazole microemulsion and its antifungal activities against Rhizoctonia solani AG1-IA.

    PubMed

    Leng, Pengfei; Zhang, Zhiming; Li, Qian; Zhang, Yunsong; Zhao, Maojun; Pan, Guangtang

    2012-06-01

    According to its physical and chemical properties, the composition of difenoconazole/propiconazole microemulsion was as follows: xylene as solvent, emulsifier HSH as surfactant and methanol as cosurfactant. The optimal formulation of difenoconazole/propiconazole microemulsion was oil/SAA/water = 1/2/5 (w/w), in which the SAA consisted of emulsifier HSH and methanol with ratio of 3/2 (w/w). The cloud point of difenoconazole/propiconazole microemulsion was 70 degrees C and its effective ingredient content was 2.5% measured by High Performance Liquid Chromatography (HPLC). Its heat storage stability was studied according to the standards. The decomposition rates of the difenoconazole/propiconazole microemulsion were merely 2.45%, 2.63% respectively and met the Food and Agriculture Organization (FAO) standards of pesticide microemulsion. Investigated by Transmission Electron Microscopy (TEM) the particle size of difenoconazole/propiconazole microemulsion was 90-140 nm and its antifungal activities against Rhizoctonia solani AG1-IA were tested and compared with that of Meiyu. We found that the inhibition rates in the difenoconazole/propiconazole microemulsion treatment group were significantly higher than that of the emulsion group with the same content of effective ingredients and the study also revealed that its inhibiting ability on the formation and germination of sclerotia was significant. PMID:22822543

  9. CAR and PXR-dependent transcriptional changes in the mouse liver after exposure to propiconazole

    EPA Science Inventory

    Exposure to the conazoles propiconazole and triadimefon but not myclobutanilled to tumors in mice after 2 years. Transcript profiling studies in the livers ofwild-type mice after short-term exposure to the conazoles revealed signatures indicating the involvement ofthe nuclear rec...

  10. INDUCTION OF CYTOCHROME P450 ISOFORMS IN RAT LIVER BY TWO CONAZOLES, TRIADIMEFON AND MYCLOBUTANIL

    EPA Science Inventory

    1. This study was undertaken to examine the inductive effects of two triazole antifungal agents, myclobutanil and triadimefon on the expression of hepatic cytochrome P450 (CYP) genes and on the activities of CYP enzymes in male Sprague-Dawley rats. Rats were dosed by gavage for 1...

  11. 40 CFR 180.434 - Propiconazole; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Propiconazole; tolerances for residues. 180.434 Section 180.434...EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances ...Propiconazole; tolerances for residues. (a) General ....

  12. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY

    EPA Science Inventory

    Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

  13. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS

    EPA Science Inventory

    Toxicogenomic analysis of five environmental contaminants was performed to investigate the ability of genomics to categorize chemicals and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole and triadimefon) and two perfluorinated compounds (...

  14. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent investigations into its carcinogenic mechanism of action. The goals of this study were: 1. To identify metabolomic changes induced in the liver by increasing doses of propiconazole in mice; 2...

  15. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent mechanistic investigations on its carcinogenic mechanism of action. The goals of this study were: 1. To identify metabolomic changes induced in the liver by increasing doses of propiconazole i...

  16. TRANSCRIPTIONAL PROFILES IN LIVER FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study (Allen et al. 2006) under...

  17. Toxicogenomic effects common to triazole antifungals and conserved between rats and humans

    SciTech Connect

    Goetz, Amber K.; Dix, David J.

    2009-07-01

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple timepoints and various study designs, gene expression profiling was conducted on rat livers from three separate studies with triazole treatment groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult exposures via feed. To explore conservation of responses across species, gene expression from the rat liver studies were compared to in vitro data from rat and human primary hepatocytes exposed to the triazoles. Toxicogenomic data on triazoles from 33 different treatment groups and 135 samples (microarrays) identified thousands of probe sets and dozens of pathways differentially expressed across time, dose, and species - many of these were common to all three triazoles, or conserved between rodents and humans. Common and conserved pathways included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver and hepatocytes were concentrated in biological pathways regulating lipid, sterol and steroid homeostasis, identifying a potential common mode of action conserved between rodents and humans. Modulation of hepatic sterol and steroid metabolism is a plausible mode of action for changes in serum testosterone and adverse reproductive outcomes observed in rat studies, and may be relevant to human risk assessment.

  18. 77 FR 75039 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ...for residues of propiconazole in or on sugarcane, cane. Syngenta Crop Protection, LLC...expressed as parent compound in or on sugarcane, cane at 1.0 parts per million...an Amended Section 3 Registration on Sugarcane'' on pages 12-18 in docket...

  19. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... . II. Summary of Petitioned-For Tolerance In the Federal Register of May 23, 2012 (Volume 77, FR 30481..., chronic, developmental and reproductive studies in animal studies. Dogs appeared to be more sensitive to... not carcinogenic to rats or to female mice. The Agency classified propiconazole as a possible...

  20. 40 CFR 180.434 - Propiconazole; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Propiconazole; tolerances for residues. 180.434 Section 180.434 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.434 Propiconazole; tolerances for...

  1. PROPICONAZOLE-INDUCED CARCINOGENESIS: ROLE OF OXIDATIVE STRESS

    EPA Science Inventory

    Propiconazole is a systemic foliar fungicide with a broad range of activity. Rodents fed with propiconazole at high dose resulted in diminished body weight, increased liver weight of adults and pups, and eventually liver carcinogenesis. In order to unravel the toxic processes inv...

  2. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J. (Waukee, IA); Ellanskaya, Irina (Kyiv, UA); Ellanskaya, legal representative, Natalia (Kyiv, UA); Gilliam, Jacob T. (Norwalk, IA); Hunter-Cevera, Jennie (Elliott City, MD); Presnail, James K. (Avondale, PA); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2009-09-15

    The invention relates to antifungal compositions and methods for protecting a plant from a fungal pathogen. Compositions including antifungal polypeptides isolated from a fungal fermentation broth are provided.

  3. Interaction of propiconazole in the peanut leafspot disease complex

    SciTech Connect

    Hancock, H.G.

    1985-01-01

    (/sup 14/C)-Propiconazole exhibited characteristics of an apoplastic xenobiotic being acropetally translocated via the transpiration stream to the foliage following root exposure in peanut (Arachis hypogeaea). When applied to leaves, radioactivity was detected distal to the point of application and accumulated along the margins of treated leaves. Redistribution to untreated plant parts was not observed. (/sup 14/C)-propiconazole rapidly penetrated the cuticle of leaves. However, leaves treated with a mixture of (/sup 14/C)-propiconazole and Penetrator 3 exhibited significantly greater foliar uptake of radioactivity than leaves treated with (/sup 14/C)-propiconazole alone. In replicated experiments, leafspot infection (caused by Cercospora arachidicola or Cercosporidium personatum) decreased quadratically with increasing application rate of Tilt 3.6EC (propiconazole) or Vangard 1.0EC (etaconazole). Combinations of fungicide and penetrator 3 gave slightly greater reductions of infection relative to fungicide alone but had no effect on yield. Propiconazole had no effect on the uptake or incorporation of (/sup 14/C)-acetate into the total lipid (TL) of peanut leaf tissue. (/sup 14/C) in the total fatty acids and non-saponifiable lipids was 10 to 20% greater, respectively, in treated tissue relative to the untreated control. Radioactivity of 4-demethyl sterols was up to 57% lower in treated leaves but no differences in radioactivity were detected in 4-methyl and 4,14-dimethyl sterols.

  4. Effects of myclobutanil on soil microbial biomass, respiration, and soil nitrogen transformations.

    PubMed

    Ju, Chao; Xu, Jun; Wu, Xiaohu; Dong, Fengshou; Liu, Xingang; Zheng, Yongquan

    2016-01-01

    A 3-month-long experiment was conducted to ascertain the effects of different concentrations of myclobutanil (0.4 mg kg(-1) soil [T1]; 1.2 mg kg(-1) soil [T3]; and 4 mg kg(-1) soil [T10]) on soil microbial biomass, respiration, and soil nitrogen transformations using two typical agricultural soils (Henan fluvo-aquic soil and Shanxi cinnamon soil). Soil was sampled after 7, 15, 30, 60, and 90 days of incubation to determine myclobutanil concentration and microbial parameters: soil basal respiration (RB), microbial biomass carbon (MBC) and nitrogen (MBN), [Formula: see text] and [Formula: see text] concentrations, and gene abundance of total bacteria, N2-fixing bacteria, fungi, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB). The half-lives of the different doses of myclobutanil varied from 20.3 to 69.3 d in the Henan soil and from 99 to 138.6 d in the Shanxi soil. In the Henan soil, the three treatments caused different degrees of short-term inhibition of RB and MBC, [Formula: see text] , and gene abundance of total bacteria, fungi, N2-fixing bacteria, AOA, and AOB, with the exception of a brief increase in [Formula: see text] content during the T10 treatment. The MBN (immobilized nitrogen) was not affected. In the Shanxi soil, MBC, the populations of total bacteria, fungi, and N2-fixing bacteria, and [Formula: see text] concentration were not significantly affected by myclobutanil. The RB and MBN were decreased transitorily in the T10 treatment. The [Formula: see text] concentrations and the abundance of both AOA and AOB were erratically stimulated by myclobutanil. Regardless of whether stimulation or suppression occurred, the effects of myclobutanil on the two soil types were short term. In summary, myclobutanil had no long-term negative effects on the soil microbial biomass, respiration, and soil nitrogen transformations in the two types of soil, even at 10-fold the recommended dosage. PMID:26590854

  5. Protein Carbonyl Formation in Response to Propiconazole-Induced Oxidative Stress.

    EPA Science Inventory

    Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propico...

  6. Effects of fungicides triadimefon and propiconazole on soil bacterial communities.

    PubMed

    Yen, Jui-Hung; Chang, Jin-Shu; Huang, Pin-Jui; Wang, Yei-Shung

    2009-09-01

    The impact of fungicides triadimefon and propiconazole on soil bacterial populations from a strawberry field was investigated. Two fungicides were applied to the soil at concentrations of 10 mg/kg or 100 mg/kg with soil water contents 20.2% (fresh soil water content) or 26.0% (field capacity). Changes in bacterial communities were assessed using DNA extraction, polymerase chain reaction (PCR) amplification of the 16S rDNA and denaturing gradient gel electrophoresis (DGGE). High performance liquid chromatography (HPLC) was utilized to detect the residue of fungicides in soils. The results showed that propiconazole was more persistent than triadimefon in soils, and the two soil water contents did not cause significant differences in dissipation rates between the two fungicides. A high concentration of propiconazole could inhibit the existence of soil microbes while one of triadimefon might induce the microbial population in the first stage. From unweighted pair-group method using arithmetic averages (UPGMA) dendrograms, the effect of triadimefon and propiconazole at the two applied concentrations on a soil bacterial community could be long term. After triadimefon was applied for 60 days and propiconazole for 75 days, the compositions of microbial communities were not recovered. From the viewpoint of environmental protection, it was of significant importance to pay more attention not only to the residues of pesticide but also to the change in soil microbial communities. PMID:20183078

  7. Occurrence of azoxystrobin, propiconazole, and selected other fungicides in US streams, 2005-2006

    USGS Publications Warehouse

    Battaglin, William A.; Sandstrom, Mark W.; Kuivila, Kathryn M.; Kolpin, Dana W.; Meyer, Michael T.

    2011-01-01

    Fungicides are used to prevent foliar diseases on a wide range of vegetable, field, fruit, and ornamental crops. They are generally more effective as protective rather than curative treatments, and hence tend to be applied before infections take place. Less than 1% of US soybeans were treated with a fungicide in 2002 but by 2006, 4% were treated. Like other pesticides, fungicides can move-off of fields after application and subsequently contaminate surface water, groundwater, and associated sediments. Due to the constant pressure from fungal diseases such as the recent Asian soybean rust outbreak, and the always-present desire to increase crop yields, there is the potential for a significant increase in the amount of fungicides used on US farms. Increased fungicide use could lead to increased environmental concentrations of these compounds. This study documents the occurrence of fungicides in select US streams soon after the first documentation of soybean rust in the US and prior to the corresponding increase in fungicide use to treat this problem. Water samples were collected from 29 streams in 13 states in 2005 and/or 2006, and analyzed for 12 target fungicides. Nine of the 12 fungicides were detected in at least one stream sample and at least one fungicide was detected in 20 of 29 streams. At least one fungicide was detected in 56% of the 103 samples, as many as five fungicides were detected in an individual sample, and mixtures of fungicides were common. Azoxystrobin was detected most frequently (45% of 103 samples) followed by metalaxyl (27%), propiconazole (17%), myclobutanil (9%), and tebuconazole (6%). Fungicide detections ranged from 0.002 to 1.15 ?/L. There was indication of a seasonal pattern to fungicide occurrence, with detections more common and concentrations higher in late summer and early fall than in spring. At a few sites, fungicides were detected in all samples collected suggesting the potential for season-long occurrence in some streams. Fungicide occurrence appears to be related to fungicide use in the associated drainage basins; however, current use information is generally lacking and more detailed occurrence data are needed to accurately quantify such a relation. Maximum concentrations of fungicides were typically one or more orders of magnitude less than current toxicity estimates for freshwater aquatic organisms or humans; however, gaps in current toxicological understandings of the effects of fungicides in the environment limit these interpretations.

  8. Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals.

    PubMed

    Kjćrstad, Mia B; Taxvig, Camilla; Nellemann, Christine; Vinggaard, Anne Marie; Andersen, Helle R

    2010-12-01

    Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole~miconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17?-estradiol (miconazole>econazole~ketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole?tebuconazole>propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity. PMID:20708073

  9. Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes

    EPA Science Inventory

    Abstract: Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen and has adverse reproductive and developmental toxicities in exp...

  10. Altered microRNA expression induced by tumorigenic conazoles in mouse liver.

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants ...

  11. A microRNA signature for tumorigenic conazoles in mouse liver.

    EPA Science Inventory

    Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants o...

  12. A potential microRNA signature for tumorigenic conazoles in mouse liver

    EPA Science Inventory

    Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumor...

  13. In vivo mutagenicity of conazole fungicides correlates with tumorigenicity

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity te...

  14. IN VIVO MUTAGENICITY OF CONAZOLE FUNGICIDES CORRELATES WITH TUMORIGENICITY-JOURNAL

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity t...

  15. Propiconazole inhibits steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

    EPA Science Inventory

    This study assessed effects of the conazole-fungicide propiconazole on endocrine function and reproductive success of the fathead minnow, using an experimental approach based on previously defined adverse outcome pathways (AOPs) for chemicals that inhibit steroidogenesis in fish...

  16. Propiconazole increases reactive oxygen species levels in mouse hepatic cells in culture and in mouse liver by a cytochrome P450 enzyme mediated process

    EPA Science Inventory

    Propiconazole induces hepatocarcinomas and hepatoadenomas in mice and is a rat liver tumor promoter. Transcriptional, proteomic, metabolomic and biochemical studies of hepatic tissues from mice treated with propiconazole under the conditions of the chronic bioassay indicate that ...

  17. Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

  18. Proteomic Analysis of Propiconazole Responses in Mouse Liver-Comparison of Genomic and Proteomic Profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this commonly used fungicide. Utilizing t...

  19. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing twodimensional...

  20. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  1. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  2. Short-term effects of propiconazole on hypothalamic-pituitary-gonadal function in the fathead minnows (Pimephales promelas)

    EPA Science Inventory

    Propiconazole is an ergosterol inhibitor commonly used in agriculture and has been detected in aquatic environments. Ergosterol inhibitors decrease fungal growth through effects on 14á-demethylase, a cytochrome P450 (CYP), isoform important for ergosterol biosynthesis. In higher ...

  3. Antifungal nanoparticles and surfaces.

    PubMed

    Paulo, Cristiana S O; Vidal, Maria; Ferreira, Lino S

    2010-10-11

    Nosocomial fungal infections, an increasing healthcare concern worldwide, are often associated with medical devices. We have developed antifungal nanoparticle conjugates that can act in suspension or attach to a surface, efficiently killing fungi. For that purpose, we immobilized covalently amphotericin B (AmB), a potent antifungal agent approved by the FDA, widely used in clinical practice and effective against a large spectrum of fungi, into silica nanoparticles. These antifungal nanoparticle conjugates are fungicidal against several strains of Candida sp., mainly by contact. In addition, they can be reused up to 5 cycles without losing their activity. Our results show that the antifungal nanoparticle conjugates are more fungistatic and fungicidal than 10 nm colloidal silver. The antifungal activity of the antifungal nanoparticle conjugates is maintained when they are immobilized on a surface using a chemical adhesive formed by polydopamine. The antifungal nanocoatings have no hemolytic or cytotoxic effect against red blood cells and blood mononuclear cells, respectively. Surfaces coated with these antifungal nanoparticle conjugates can be very useful to render medical devices with antifungal properties. PMID:20845938

  4. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish.

    PubMed

    Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen

    2016-01-01

    Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53(-/-) mutant of medaka fish (Oryzias latipes) to propiconazole (2.5-250?g/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53(-/-) mutant medaka with early life exposure to propiconazole showed increased incidence of hepatocarcionogensis, as compared to the p53(-/-) control group and wild type strain. We demonstrated that propiconazole can initiate ROS-mediated oxidative stress and induce hepatic tumorigenesis associated with CYP1A- and/or p53 -mediated pathways with the use of wild type and p53(-/-) mutant of medaka fish. The toxic response of medaka to propiconazole is compatible with that observed in rodents. PMID:26619215

  5. Propiconazole enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras famesylation

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic ...

  6. Loss of Propiconazole and its Four Stereoisomers from the Water Phase of Two Soil-Water Slurries as Measured by Capillary Electrophoresis

    EPA Science Inventory

    Propiconazole is a chiral fungicide used in agriculture for control of many fungal diseases on a variety of crops. This use provides opportunities for pollution of soil and, subsequently, groundwater. The rate of loss of propiconazole from the water phase of two different soil-wa...

  7. Antifungal Compounds from Cyanobacteria

    PubMed Central

    Shishido, Tânia K.; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P.; Permi, Perttu; Andreote, Ana P. D.; Fiore, Marli F.; Sivonen, Kaarina

    2015-01-01

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders. PMID:25871291

  8. Evaluation of the reproductive toxicity of fungicide propiconazole in male rats.

    PubMed

    Costa, Nathália Orlandini; Vieira, Milene Leivas; Sgarioni, Vanessa; Pereira, Marina Rangel F; Montagnini, Bruno Garcia; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

    2015-09-01

    The propiconazole (Prop) is a fungicide extensively used in agriculture. There are evidences that this compound may cause endocrine disrupting effects. In vitro studies have demonstrated that Prop inhibits the activity of CYP 19 (aromatase), responsible for converting androgens into estrogens and also is an androgen and estrogen receptor antagonist. Therefore, this study evaluated the reproductive toxicity of Prop treatment in male rats. The Wistar rats were divided in three groups and were treated daily, by gavage, with corn oil (control group), propiconazole 4 mg/kg (Prop 4) and 20 mg/kg (Prop 20), from post-natal day 50 to 120. The following were observed: the body weight gain, sexual behavior, testosterone and estradiol plasmatic levels, organs weight, sperm count and morphology and testicular histomorphology. There was an increase in abnormal tail morphology sperm, seminal vesicle and vas deferens weight, and a decrease in estradiol levels in Prop 4 group. Sexual behavior was affected only in the Prop 20 group. These results suggest that Prop treatment induced alterations in some reproductive parameters, what could be related with an endocrine disruption. PMID:26169826

  9. Antifungal Amphiphilic Aminoglycosides.

    PubMed

    Chang, C-W T; Takemoto, J Y

    2014-08-01

    The attachment of alkyl and other hydrophobic groups to traditional antibacterial kanamycins and neomycins creates amphiphilic aminoglycosides with altered antimicrobial properties. In this review, we summarize the discovery of amphiphilic kanamycins that are antifungal, but not antibacterial, and that inhibit the growth of fungi by perturbation of plasma membrane functions. With low toxicities against plant and mammalian cells, they appear to specifically target the fungal plasma membrane. These new antifungal agents offer new options for fighting fungal pathogens and are examples of reviving old drugs to confront new therapeutic challenges. PMID:25110571

  10. Antifungal Amphiphilic Aminoglycosides

    PubMed Central

    Chang, C.-W. T.; Takemoto, J.Y.

    2014-01-01

    The attachment of alkyl and other hydrophobic groups to traditional antibacterial kanamycins and neomycins creates amphiphilic aminoglycosides with altered antimicrobial properties. In this review, we summarize the discovery of amphiphilic kanamycins that are antifungal, but not antibacterial, and that inhibit the growth of fungi by perturbation of plasma membrane functions. With low toxicities against plant and mammalian cells, they appear to specifically target the fungal plasma membrane. These new antifungal agents offer new options for fighting fungal pathogens and are examples of reviving old drugs to confront new therapeutic challenges. PMID:25110571

  11. Residues and dissipation kinetics of triazole fungicides difenoconazole and propiconazole in wheat and soil in Chinese fields.

    PubMed

    Zhang, Zhiyong; Jiang, Wayne; Jian, Qiu; Song, Wencheng; Zheng, Zuntao; Wang, Donglan; Liu, Xianjin

    2015-02-01

    An analytical method for simultaneously determining the residues of difenoconazole and propiconazole in wheat straw, wheat grain and soil was developed. Mean recoveries and relative standard deviations in all samples ranged 86.2-101.3% and 3.1-12.1% for propiconazole and difenoconazole. The half-lives of difenoconazole and propiconazole were 3.6-5.5days and 5.1-6.9days in wheat straws, and 4.9-5.8days and 6.1-8.4days in soil, respectively. The residues in wheat grain were found to be <0.01mg/kg, based on the application rate (135g a.i./ha) and the pre-harvest interval (PHI=28days) recommended by the manufacturer. The results suggest that the use of difenoconazole and propiconazole on wheat is considered to be safe under the Good Agricultural Practices (GAP) in the Chinese fields, and the main factors for pesticide residue in crops are application times, rates and pre-harvest intervals. PMID:25172726

  12. Propiconazole-enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras farnesylation

    SciTech Connect

    Murphy, Lynea A.; Moore, Tanya; Nesnow, Stephen

    2012-04-15

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2 activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular fractions from control, MVAL or propiconazole-treated cells revealed increased Ras protein in the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL reversed these effects. Western blot analysis indicated that phosphorylation of Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data indicate that propiconazole increases cell proliferation by increasing the levels of cholesterol biosynthesis intermediates presumably through a negative feedback mechanism within the pathway, a result of CYP51 inhibition. This feedback mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation. These results provide an explanation for the observed effects of propiconazole on hepatic cholesterol pathways and on the increased hepatic cell proliferation induced by propiconazole in mice. Highlights: ? Propiconazole increases cell proliferation in AML12 mouse hepatocytes. ? Propiconazole increases Ras farnesylation and alters Ras membrane localization. ? Propiconazole increases Erk1/2 phosphorylation. ? Dysregulation of the cholesterol biosynthesis pathway can explain these results. ? These results can explain similar effects induced by propiconazole in mice.

  13. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive ?,?-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen–Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  14. PROPICONAZOLE-INDUCED CYTOCHROME P450 GENE EXPRESSION AND ENZYMATIC ACTIVITIES IN RAT AND MOUSE LIVER

    EPA Science Inventory

    Conazoles are N-substituted azole antifungal agents used as both pesticides and drugs. Some of these compounds are hepatocarcinogenic in mice and some can induce thyroid tumors in rats. Many of these compounds are able to induce and/or inhibit mammalian hepatic cytochrome P450s t...

  15. The hepatocarcinogenic conazoles: cyproconazole, epoxiconazole, and propiconazole induce a common set of toxicological and transcriptional responses.

    PubMed

    Hester, Susan; Moore, Tanya; Padgett, William T; Murphy, Lynea; Wood, Charles E; Nesnow, Stephen

    2012-05-01

    Conazoles are fungicides used as agricultural pesticides and pharmaceutical products. We investigated whether a common core of toxicological and transcriptional responses underlies the observed carcinogenic effects of three conazoles: cyproconazole, epoxiconazole, and propiconazole. In studies where mice were fed diets of these conazoles for 30 days, we found a common set of toxicological effects altered by these conazoles: hepatomegaly, hepatocellular hypertrophy, decreased serum cholesterol, decreased hepatic levels of all-trans-retinoic acid, and increased hepatic cell proliferation. Microarray-based transcriptional analysis revealed 330 significantly altered probe sets common to these conazoles, many of which showed strong dose responses for cytochrome P450, glutathione S-transferase, and oxidative stress genes. More detailed analyses identified a subset of 80 altered genes common to the three conazoles that were associated with cancer. Pathways associated with these genes included xenobiotic metabolism, oxidative stress, cell signaling, and cell proliferation. A common TGF?-centric pathway was identified within the 80-gene set, which, in combination with the toxicological and other transcriptomic findings, provides a more refined toxicity profile for these carcinogenic conazoles. PMID:22334560

  16. Molecular impact of propiconazole on Daphnia magna using a reproduction-related cDNA array.

    PubMed

    Soetaert, Anneleen; Moens, Lotte N; Van der Ven, Karlijn; Van Leemput, Koen; Naudts, Bart; Blust, Ronny; De Coen, Wim M

    2006-01-01

    We have developed a first version cDNA microarray of the cladoceran Daphnia magna. Through Suppression Subtractive Hybridisation PCR (SSH-PCR) 855 life stage-specific cDNAs were collected and used to document the toxicological mode of action of the pesticide propiconazole. DNA sequencing analysis revealed gene fragments related to important functional classes such as embryo development, energy metabolism, molting and cell cycle. Major changes in transcription were observed in organisms exposed for 4 and 8 days to 1 microg/mL. After 4 days a 3-fold down-regulation of the gene encoding the yolk protein, vitellogenin, was observed indicating impaired oocyte maturation. Moreover, genes such as a larval-specific gene and chaperonin were repressed, whereas the heat shock 90 protein and ATP synthase were induced. Organismal effects clearly confirmed the major molecular findings: at the highest concentration (1 microg/mL) adult growth was significantly (p < 0.05) impaired and increased developmental effects in the offspring could be noted. We have demonstrated the potential of microarray analysis in toxicity screening with D. magna. The use of vitellogenin mRNA as a rapid biomarker of reproductive effects in chronic toxicity studies with cladocerans is suggested. PMID:16311075

  17. Insight into the antifungal mechanism of Neosartorya fischeri antifungal protein.

    PubMed

    Virágh, Máté; Marton, Annamária; Vizler, Csaba; Tóth, Liliána; Vágvölgyi, Csaba; Marx, Florentine; Galgóczy, László

    2015-07-01

    Small, cysteine-rich, highly stable antifungal proteins secreted by filamentous Ascomycetes have great potential for the development of novel antifungal strategies. However, their practical application is still limited due to their not fully clarified mode of action. The aim of this work was to provide a deep insight into the antifungal mechanism of Neosartorya fischeri antifungal protein (NFAP), a novel representative of this protein group. Within a short exposure time to NFAP, reduced cellular metabolism, apoptosis induction, changes in the actin distribution and chitin deposition at the hyphal tip were observed in NFAP-sensitive Aspergillus nidulans. NFAP did show neither a direct membrane disrupting-effect nor uptake by endocytosis. Investigation of A. nidulans signalling mutants revealed that NFAP activates the cAMP/protein kinase A pathway via G-protein signalling which leads to apoptosis and inhibition of polar growth. In contrast, NFAP does not have any influence on the cell wall integrity pathway, but an unknown cell wall integrity pathway-independent mitogen activated protein kinase A-activated target is assumed to be involved in the cell death induction. Taken together, it was concluded that NFAP shows similarities, but also differences in its mode of antifungal action compared to two most investigated NFAP-related proteins from Aspergillus giganteus and Penicillium chrysogenum. PMID:25994413

  18. Variation in sorption of propiconazole with biochars: The effect of temperature, mineral, molecular structure, and nano-porosity.

    PubMed

    Sun, Ke; Kang, Mingjie; Ro, Kyoung S; Libra, Judy A; Zhao, Ye; Xing, Baoshan

    2016-01-01

    Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal waste-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) (300, 450 and 600°C) (e.g., BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 was investigated. PLABs belonged to high- or medium-C biochars and ANIBs were low-C biochars. Surface C concentrations of the tested biochars were generally higher than their corresponding bulk C. Surface polar groups were mainly composed of O-containing groups of minerals within biochars. The nonlinearity coefficients (n) of propiconazole (PROPI) sorption isotherms ranged from 0.23 to 0.64, which was significantly and negatively related to organic carbon (OC)-normalized CO2-surface area (CO2-SA/OC) of biochars. This correlation along with the positive relationship between CO2-SA/OC and aromaticity indicates that pore-filling in nanopores within aromatic C dominate nonlinear PROPI sorption. HTTs or C contents do not necessarily regulate PROPI sorption. Removal of minerals from BCs450 elevated PROPI sorption because minerals may exert certain influence on sorption via impacting spatial arrangement of polar groups and/or organic matter (OM)-mineral interactions. This study helps to better understand sorption behavior of PROPI to biochars and evaluate the potential role of biochar in water treatment systems. PMID:26206746

  19. Letter to the Editor, Response to Commentary "Re-Evaluation of the Big Blue® Mouse Assay of Propiconazole Suggests Lack of Mutagenicity"

    EPA Science Inventory

    In their commentary titled "Re-Evaluation of the Big Blue® Mouse Assay of Propiconazole Suggests Lack of Mutagenicity", Shane et 01. present an overview of portions of our previously reported work examining the potential for some conazole fungicides to induce increases in mutant ...

  20. Antifungal activity of juniper extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sawdust from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane or ethanol and the extracts tested for antifungal activity against four species of wood-rot fungi. These species studied represent the junipers with the greatest potential for co...

  1. New antifungal and antiviral dosing.

    PubMed

    Wade, Kelly C; Monk, Heather M

    2015-03-01

    Neonatal fungal and viral infections are associated with mortality and neurologic impairment among survivors. Advances in pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial medications have led to improved dosing guidance for neonates. This article discusses the basic PK/PD properties and dosing of the most common antifungal and antiviral medications used in neonates. PMID:25678004

  2. Antibacterial and Antifungal Compounds from Marine Fungi

    PubMed Central

    Xu, Lijian; Meng, Wei; Cao, Cong; Wang, Jian; Shan, Wenjun; Wang, Qinggui

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review. PMID:26042616

  3. Defensins: antifungal lessons from eukaryotes

    PubMed Central

    Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

    2014-01-01

    Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

  4. Quantitative changes in endogenous DNA damage correlate with conazole mutagenicity and tumorigenicity.

    EPA Science Inventory

    The mouse liver tumorigenic conazolefungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil w...

  5. COMPARISON OF HEPATIC GENE EXPRESSION PROFILES FROM MICE EXPOSED TO THREE TOXICOLOGICALLY DIFFERENT CONAZOLES

    EPA Science Inventory

    Conazoles comprise a chemical class of fungicides used as agricultural and pham-taceutical products. Both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen. The tumorigenic activities of these conazoles ...

  6. CHARACTERIZATION OF CYPS IN THE METABOLISM OF ALL TRANS RETINOIC ACID BY LIVER MICROSOMES FROM MICE TREATED WITH CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may involve in conazole-...

  7. COMPARISON OF GENE EXPRESSION PROFILES FROM RATS FED THREE TOXICOLOGICALLY DIFFERENT CONAZOLES

    EPA Science Inventory

    Conazoles arc a class of fungicides used as pharmaceutical and agricultural products. In chronic bioassays, triadimefon was hepatotoxic and induced transitional cell adenomas in the thyroid gland. Both propiconazole and myclobutanil were hepatotoxic but had no effect on the thyro...

  8. ALTERATIONS IN A11 TRANS RETINOIC ACID METABOLISM IN LIVER MICROSOMES FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may be a key event in co...

  9. DIFFERENTIAL EXPRESSION OF RETINOIC ACID BIOSYNTHETIC AND METABOLISM GENES IN LIVERS FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may play a key event in ...

  10. RAMAN SPECTROSCOPY-BASED METABOLOMICS FOR DIFFERENTIATING EXPOSURES TO TRIAZOLE FUNGICIDES USING RAT URINE

    EPA Science Inventory

    Normal Raman spectroscopy was evaluated as a metabolomic tool for assessing the impacts of exposure to environmental contaminants, using rat urine collected during the course of a toxicological study. Specifically, one of three triazole fungicides, myclobutanil, propiconazole or ...

  11. Gene Expression Profiling in Liver and Testis of Rats to Characterize the Toxicity of Triazole Fungicides

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  12. GENE EXPRESSION PROFILING IN LIVER AND TESTIS OF RATS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES.

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  13. Ultraviolet induction of antifungal activity in plants.

    PubMed

    Schumpp, O; Bruderhofer, N; Monod, M; Wolfender, J-L; Gindro, K

    2012-11-01

    Ultraviolet-C irradiation as a method to induce the production of plant compounds with antifungal properties was investigated in the leaves of 18 plant species. A susceptibility assay to determine the antifungal susceptibility of filamentous fungi was developed based on an agar dilution series in microtiter plates. UV irradiation strongly induced antifungal properties in five species against a clinical Fusarium solani strain that was responsible for an onychomycosis case that was resistant to classic pharmacological treatment. The antifungal properties of three additional plant species were either unaffected or reduced by UV-C irradiation. This study demonstrates that UV-C irradiation is an effective means of modulating the antifungal activity of very diverse plants from a screening perspective. PMID:22509892

  14. Biofilms and Antifungal Susceptibility Testing.

    PubMed

    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. PMID:26519074

  15. The antifungal action of dandruff shampoos.

    PubMed

    Bulmer, A C; Bulmer, G S

    1999-01-01

    The disease commonly known as "dandruff" is caused by numerous host factors in conjunction with the normal flora yeast Malassezia furfur (Pityrosporum ovale). Indeed, clinical studies have shown that administration of antifungal agents correlates with an improved clinical condition. Almost all commercially available hair shampoos publicize that they contain some form of antifungal agent(s). However, few studies have been published in which antifungal activity of commercially available hair shampoos have been contrasted experimentally. In this study six commercially available shampoos (in the Philippines) were assessed for antifungal activity against a human (dandruff) isolate of M. furfur: (a) Head & Shoulders (Proctor & Gamble); (b) Gard Violet (Colgate-Palmolive); (c) Nizoral 1% (Janssen); (d) Nizoral 2% (Janssen); (e) Pantene Blue (Proctor & Gamble); and (f) Selsun Blue (Abbott). The results demonstrated that all six of the assayed hair shampoos have some antifungal effect on the test yeast. However, there was consider variation in potency of antifungal activity. Nizoral 1% and Nizoral 2% shampoo preparations were the most effective. The 1% Nizoral shampoo was consistently 10X better at killing yeast cells than the next closest rival shampoo. The 2% Nizoral shampoo was 10X better than the Nizoral 1% product and 100 times better than any of the other products assayed. The study demonstrated that shampoos containing a proven antifungal compound were the most effective in controlling the causative yeast. PMID:10967964

  16. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  17. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

    Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. Ketoconazole Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I˛ = 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 encounte

  18. New Antifungal Pyranoisoflavone from Ficus tikoua Bur.

    PubMed Central

    Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

    2012-01-01

    Considering the undesirable attributes of synthetic fungicides and the availability of Ficus species in China, the stem of Ficus tikoua Bur. was investigated. One new antifungal pyranoisoflavone, 5,3?,4?-trihydroxy-2?,2?-dimethylpyrano (5?,6?:7,8) isoflavone (1), together with two known isoflavones, wighteone (2) and lupiwighteone (3) (with previously reported antifungal activities), were isolated from ethyl acetate extract by bioassay-guided fractionation. Their structures were determined by spectroscopic analysis, such as NMR (1H-1H COSY, HMQC, HMBC and NOESY), IR, UV and HRMS, as well as ESI-MSn analyses. The antifungal activities of 1–3 against Phytophthora infestans were evaluated by direct spore germination assay, and the IC50 values were 262.442, 198.153 and 90.365 ?g·mL?1, respectively. PMID:22837700

  19. Rechargeable infection-responsive antifungal denture materials.

    PubMed

    Cao, Z; Sun, X; Yeh, C-K; Sun, Y

    2010-12-01

    Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin discs were sustained for a prolonged period of time (weeks and months). Drug release was much faster at acidic conditions (pH 5) than at pH 7. Drugs bound to the denture materials could be "washed out" by treatment with EDTA, and the drug-depleted resins could be recharged with the same or a different class of anticandidal drugs. These results suggest clinical potential of the newly developed antifungal denture materials in the management of CADS and other infectious conditions. PMID:20940361

  20. Candida endocarditis: role of new antifungal agents.

    PubMed

    Talarmin, J P; Boutoille, D; Tattevin, P; Abgueguen, P; Ansart, S; Roblot, F; Raffi, F

    2009-01-01

    Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report seven cases, which occurred during a period of 1 year in western France. Six cases were because of Candida albicans, and one pacemaker endocarditis was because of Candida parapsilosis. All patients were men and presented risk factors for candidaemia. Of the six patients with valvular involvement, five received caspofungin and two had surgical valve replacement. Three patients treated with caspofungin antifungal therapy without valve replacement were cured from endocarditis. Antifungal and surgical strategies are discussed, in particular, the possible role of new antifungal therapies and long-term suppression therapy without surgery. One patient died in the acute phase of endocarditis, three patients died of causes unrelated to infective endocarditis and three patients had a favourable outcome. PMID:18498304

  1. Antifungal effect of some spice hydrosols.

    PubMed

    Boyraz, Nuh; Ozcan, Musa

    2005-12-01

    The antifungal effects of rosemary, cumin, sater (savory), basil and pickling herb hydrosols were investigated against Rhizoctonia solani, Fusarium oxysporum f. sp tulipae, Botrytis cinerea and Alternaria citri. Hydrosols of sater and pickling herb showed the most relevant fungicidal activity. PMID:16243447

  2. Synthetic Multivalent Antifungal Peptides Effective against Fungi

    PubMed Central

    Li, Jianguo; Nandhakumar, Muruganantham; Aung, Thet Tun; Goh, Eunice; Chang, Jamie Ya Ting; Saraswathi, Padhmanaban; Tang, Charles; Safie, Siti Radiah Binte; Lin, Lim Yih; Riezman, Howard; Lei, Zhou; Verma, Chandra S.; Beuerman, Roger W.

    2014-01-01

    Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2–4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. PMID:24498363

  3. Efflux-mediated antifungal drug resistance.

    PubMed

    Cannon, Richard D; Lamping, Erwin; Holmes, Ann R; Niimi, Kyoko; Baret, Philippe V; Keniya, Mikhail V; Tanabe, Koichi; Niimi, Masakazu; Goffeau, Andre; Monk, Brian C

    2009-04-01

    Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps. PMID:19366916

  4. Efflux-Mediated Antifungal Drug Resistance†

    PubMed Central

    Cannon, Richard D.; Lamping, Erwin; Holmes, Ann R.; Niimi, Kyoko; Baret, Philippe V.; Keniya, Mikhail V.; Tanabe, Koichi; Niimi, Masakazu; Goffeau, Andre; Monk, Brian C.

    2009-01-01

    Summary: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps. PMID:19366916

  5. Synthetic multivalent antifungal peptides effective against fungi.

    PubMed

    Lakshminarayanan, Rajamani; Liu, Shouping; Li, Jianguo; Nandhakumar, Muruganantham; Aung, Thet Tun; Goh, Eunice; Chang, Jamie Ya Ting; Saraswathi, Padhmanaban; Tang, Charles; Safie, Siti Radiah Binte; Lin, Lim Yih; Riezman, Howard; Lei, Zhou; Verma, Chandra S; Beuerman, Roger W

    2014-01-01

    Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. PMID:24498363

  6. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  7. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    PubMed Central

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  8. In vitro antifungal susceptibility of coelomycete agents of black grain eumycetoma to eight antifungals.

    PubMed

    Ahmed, Sarah Abdalla; de Hoog, G Sybren; Stevens, David A; Fahal, Ahmed H; van de Sande, Wendy W J

    2015-04-01

    Fungal mycetoma (eumycetoma) represents one of the most difficult infections to appropriately manage. The current recommended treatment is based on extensive surgical debridement combined with prolonged antifungal therapy with ketoconazole or itraconazole. Despite the different phylogenetic positions of black-grain eumycetoma species, they are all treated with the same antifungal agents. The in vitro antifungal susceptibility of coelomycetous eumycetoma agents in the order of Pleosporales presently is largely unknown. Here we determined the in vitro activity of eight antifungal agents against seven species causing human eumycetoma using the Sensititre YeastOne method. High minimum inhibitory concentrations (MICs) were found with fluconazole, caspofungin, flucytosine, and amphotericin B. Voriconazole and posaconazole were found to be active against all species tested. Of the species included in the investigation, MICs of Medicopsis romeroi differed from the rest of the mycetoma causative agents belonging to the order of the Pleosporales. We found significantly lower MICs for amphotericin B and significantly higher MICs for fluconazole, ketoconazole, and itraconazole against this species. Our results emphasised that identification of black grain mycetoma agent is important as well as performing susceptibility testing before starting of antifungal treatment. PMID:25631481

  9. A new antifungal coumarin from Clausena excavata.

    PubMed

    Kumar, Ramashish; Saha, Aniruddha; Saha, Dipanwita

    2012-01-01

    A new ?-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2-enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human pathogen, Candida tropicalis and the plant pathogens Rhizoctonia solani and Sclerotinia sclerotiorum. Antifungal activities against the human pathogens, Aspergillus fumigatus and Mucor circinelloides and plant pathogens, Colletotrichum gloeosporioides, Lasiodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were stronger than that of the standard antimicrobials. PMID:22088496

  10. Current and Emerging Azole Antifungal Agents

    PubMed Central

    Sheehan, Daniel J.; Hitchcock, Christopher A.; Sibley, Carol M.

    1999-01-01

    Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided. PMID:9880474

  11. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    PubMed Central

    Ascacio-Valdés, Juan; Burboa, Edgardo; Aguilera-Carbo, Antonio F; Aparicio, Mario; Pérez-Schmidt, Ramón; Rodríguez, Raúl; Aguilar, Cristóbal N

    2013-01-01

    Objective To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica (E. antisyphilitica) Zucc in the wax extraction process. Methods An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16, until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder. An aqueous solution was prepared and treated through ionic exchange liquid chromatography (Q XL) and gel permeation chromatography (G 25). The ellagitannin-rich fraction was thermogravimetrically evaluated (TGA and DTA) to test the thermo-stability of ellagic acid (monomeric unit). Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and, also mass spectroscopy was used to determine the molecular ion. Results The principal functional groups of ellagitannin were determined, the molecular weight was 860.7 g/mol; and an effective antifungal activity against phytopathogenic fungi was demonstrated. Conclusions It can be concluded that the new ellagitannin (860.7 g/mol) isolated from E. antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata, Fusarium oxyzporum, Colletotrichum gloeosporoides and Rhizoctnia solani. PMID:23570015

  12. Antifungal Resistance and New Strategies to Control Fungal Infections

    PubMed Central

    Vandeputte, Patrick; Ferrari, Selene; Coste, Alix T.

    2012-01-01

    Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology. PMID:22187560

  13. Mutation Spectrum Induced by Conazole Fungicides in LacI Transgenic C57BL/6 Mouse Liver.

    EPA Science Inventory

    Conazoles are antifungal agents used in both agricultural and pharmaceutical settings. Some conazoles, including propiconazole and triadimefon, induce hepatocellular tumors in mice, while other conazoles do not. We reported in a previous study that both propiconazole and triadime...

  14. Optimization of Antifungal Extracts from Ficus hirta Fruits Using Response Surface Methodology and Antifungal Activity Tests.

    PubMed

    Chen, Chuying; Wan, Chunpeng; Peng, Xuan; Chen, Yuhuan; Chen, Ming; Chen, Jinyin

    2015-01-01

    The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio and temperature, were chosen to identify their effects on the diameters of inhibition zones (DIZs) against these two Penicillium molds. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimal extraction parameters for maximum antifungal activity were: 90% (v/v) ethanol concentration, 65 min extraction time, 31 mL/g solvent to solid ratio and 51 °C temperature. Under the abovementioned extraction conditions, the experimental DIZs values obtained experimentally were 57.17 ± 0.75 and 39.33 ± 0.82 mm, which were very close to the values of 57.26 and 39.29 mm predicted by the model. Further, nine kinds of phytopathogens were tested in vitro to explore the antifungal activity of the FH extracts. It was found for the first time that the FH extracts showed significant inhibition on the growth of P. italicum, A. citri, P. vexans, P. cytosporella and P. digitatum. PMID:26528961

  15. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  16. Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil

    PubMed Central

    Vieira, Silvia Cristina Heredia; de Paulo, Luis Fernando; Svidzinski, Terezinha Inez Estivaleti; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; de Souza, Amanda; Young, Maria Cláudia Marx; Cortez, Diógenes Aparício Garcia

    2011-01-01

    In vitro activity of the essential oil from Piper diospyrifolium leaves was tested using disk diffusion techniques. The antifungal assay showed significant potencial antifungal activity: the oil was effective against several clinical fungal strains. The majority compounds in the essential oil were identified as sesquiterpenoids by GC-MS and GC-FID techniques. PMID:24031717

  17. Synthesis, antifungal, and phytotoxic effects of some benzopyrone derivatives.

    PubMed

    Khan, Khalid Mohammed; Saify, Zafar S; Khan, Muhammad Zarrar; Hayat, Safdar; Begum, Saeedan; Noor, Fatima; Choudhary, M Iqbal; Perveen, Shahnaz; Atta-Ur-Rahman

    2004-02-01

    Syntheses of benzopyrones 1, 13, and their derivatives, as well as their phytotoxic (in vitro) and antifungal (in vitro) screening was carried out. Compounds 2, 7, 8, and 10 showed significant phytotoxic activity, whereas 3, 8, 10, and 12 exhibited significant antifungal (in vitro) activity. PMID:14974613

  18. Antifungal and antiviral products of marine organisms.

    PubMed

    Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper ?-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry. PMID:24562325

  19. Microbial Biotransformation to Obtain New Antifungals

    PubMed Central

    Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact.

  20. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    PubMed

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. PMID:26586600

  1. Novel drug delivery strategies for improving econazole antifungal action.

    PubMed

    Firooz, Alireza; Nafisi, Shohreh; Maibach, Howard I

    2015-11-10

    Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections. PMID:26383840

  2. Antifungal activities of ethanolic extract from Jatropha curcas seed cake.

    PubMed

    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. PMID:20208435

  3. Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components.

    PubMed

    Jiang, Hongxia; Wang, Xiaohui; Xiao, Chengze; Wang, Weiyan; Zhao, Xu; Sui, Junkang; Sa, Rongbo; Guo, Tai L; Liu, Xunli

    2015-10-01

    The establishment of safe and effective methods for controlling fungal disease is an urgent issue in agriculture and forestry. Microbiological control of plant disease is expected to achieve better results than use of chemically derived fungicides. This study aimed to establish Brevibacillus laterosporus JX-5 as a potential microbiological control agent of poplar canker. The bacterium was isolated from the poplar rhizosphere and demonstrated significant growth inhibition of several pathogenic fungi in vitro. The antifungal components of Br. laterosporus JX-5 were isolated and identified. The fermentation broth of Br. laterosporus JX-5 and its main antifungal component, designated as component B, reduced Botryosphaeria dothidea associated canker of the excised poplar branch by 70 and 90%, respectively. Component B is considerably heat-stable, adaptable to a broad pH range, and UV-resistant. It could inhibit Bo. dothidea by permeating the fungal membrane, fracturing the nuclei, damaging the cell wall, and eventually killing the pathogenic fungus. The antifungal activity exhibited by Br. laterosporus JX-5 and its bioactive metabolic products indicate its feasibility as a potential biocontrol agent for plant diseases. PMID:26265360

  4. Antifungal Susceptibilities of Bloodstream Isolates of Candida Species from Nine Hospitals in Korea: Application of New Antifungal Breakpoints and Relationship to Antifungal Usage

    PubMed Central

    Won, Eun Jeong; Shin, Jong Hee; Choi, Min Ji; Lee, Wee Gyo; Park, Yeon-Joon; Uh, Young; Kim, Shine-Young; Lee, Mi-Kyung; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

    2015-01-01

    We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ?4 ?g/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman’s correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ?4 ?g/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI. PMID:25706866

  5. Overview of medically important antifungal azole derivatives.

    PubMed Central

    Fromtling, R A

    1988-01-01

    Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739). PMID:3069196

  6. Antifungal saponins from Paris polyphylla Smith.

    PubMed

    Deng, Dawei; Lauren, Denis R; Cooney, Janine M; Jensen, Dwayne J; Wurms, Kirstin V; Upritchard, Jenine E; Cannon, Richard D; Wang, Ming Zhong; Li, Ming Zhang

    2008-09-01

    Three steroidal saponins, including one new and two known compounds, were isolated from the rhizomes of Paris polyphylla Smith. One- and two-dimensional NMR, LC-MS, and interpretation of hydrolytic cleavage experiments led to the identification of the structure of the new saponin as ( 25R)-spirost-5-ene-3 beta,17 alpha-diol (pennogenin) 3- O-{ O- alpha- L-rhamnopyranosyl-(1-->2)- O-[ O- beta-xylopyranosyl-(1-->5)- alpha- L-arabinofuranosyl-(1-->4)]- beta- D-glucopyranoside}. The isolated saponins were evaluated for their antifungal activity against Cladosporium cladosporioides and Candida species and showed comparable activity to chemicals used in some commercial products. PMID:18729041

  7. A new antifungal metabolite from Penicillium expansum.

    PubMed

    He, Guochun; Matsuura, Hideyuki; Takushi, Tetsuya; Kawano, Shinji; Yoshihara, Teruhiko

    2004-07-01

    A new antifungal compound, (3S)-4,6-dihydro-8-methoxy-3,5-dimethyl-6-oxo-3H-2-benzopyran (4), was isolated from Penicillium expansum. During the isolation procedure 4 was determined to be unstable and readily reacted with methanol, ethanol, and water, forming three new isochromans, (1S,3S)-6-hydroxy-1,8-dimethoxy-3,5-dimethylisochroman (1), 1-ethoxy-6-hydroxy-8-methoxy-3,5-dimethylisochroman (2), and 1,6-dihydroxy-8-methoxy-3,5-dimethylisochroman (3), respectively. (3S)-6-Hydroxy-8-methoxy-3,5-dimethylisochroman (5) was reisolated from P. expansum. In fungicide disk assays, compounds 1, 2, and 4 inhibited the mycelial growth of Lasiodiplodia theobromae at 100 microg/mL by 76%, 74%, and 69%, respectively. PMID:15270557

  8. 21 CFR 333.250 - Labeling of antifungal drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of antifungal drug products. 333.250 Section 333.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  9. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    PubMed

    Kfoury, Miriana; Lounčs-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélčne; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability. PMID:26593522

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

    PubMed

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

    2015-11-01

    In the present study, in vitro antifungal activities of five antipsychotic drugs (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ; amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB; caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were investigated in broth microdilution tests against four clinical and five environmental Scedosporium and Pseudallescheria isolates. When used alone, phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in vitro combinations with AMB, CSP, VRC, and TRB were also examined against the clinical isolates. In combination with antifungal agents, CPZ was able to act synergistically with AMB and TRB in cases of one and two isolates, respectively. In all other cases, indifferent interactions were revealed. Antagonism was not observed between the tested agents. These combinations may establish a more effective and less toxic therapy after further in vitro and in vivo studies for Scedosporium and Pseudallescheria infections. PMID:26316212

  11. Macrocyclic trichothecenes as antifungal and anticancer compounds.

    PubMed

    de Carvalho, Maira Peres; Weich, Herbert; Abraham, Wolf-Rainer

    2016-01-01

    Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy. PMID:26572613

  12. Terbinafine: novel formulations that potentiate antifungal activities.

    PubMed

    Ma, Y; Chen, X; Guan, S

    2015-03-01

    Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. PMID:25876563

  13. Antifungal and antibacterial activity of marine microorganisms.

    PubMed

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

    2014-03-01

    In order to explore marine microorganisms with pharmaceutical potential, marine bacteria, collected from different coastal areas of the Moroccan Atlantic Ocean, were previously isolated from seawater, sediment, marine invertebrates and seaweeds. The antimicrobial activities of these microorganisms were investigated against the pathogens involved in human pathologies. Whole cultures of 34 marine microorganisms were screened for antimicrobial activities using the method of agar diffusion against three Gram-positive bacteria, two Gram-negative bacteria, and against yeast. The results showed that among the 34 isolates studied, 28 (82%) strains have antimicrobial activity against at least one pathogen studied, 11 (32%) strains have antifungal activity and 24 (76%) strains are active against Gram-positive bacteria, while 21 (62%) strains are active against Gram-negative bacteria. Among isolates having antimicrobial activity, 14 were identified and were assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms can produce antibiotic substance; therefore, these marine microorganisms were expected to be potential resources of natural antibiotic products. PMID:24630312

  14. Antifungal hydroxy fatty acids produced during sourdough fermentation: microbial and enzymatic pathways, and antifungal activity in bread.

    PubMed

    Black, Brenna A; Zannini, Emanuele; Curtis, Jonathan M; Gänzle, Michael G

    2013-03-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C(18:1) fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter(-1). Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter(-1). L. hammesii accumulated the monohydroxy C(18:1) fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter(-1) (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread. PMID:23315734

  15. Antifungal Hydroxy Fatty Acids Produced during Sourdough Fermentation: Microbial and Enzymatic Pathways, and Antifungal Activity in Bread

    PubMed Central

    Black, Brenna A.; Zannini, Emanuele; Curtis, Jonathan M.

    2013-01-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C18:1 fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter?1. Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter?1. L. hammesii accumulated the monohydroxy C18:1 fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter?1 (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread. PMID:23315734

  16. Exploring the molecular basis of antifungal synergies using genome-wide approaches

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Antifungal activity of essential oils against selected terverticillate penicillia.

    PubMed

    Felšöciová, So?a; Ka?ániová, Miroslava; Horská, Elena; Vukovi?, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stri?ík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis. PMID:25780826

  18. 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 ?g/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.

  19. Natural products--antifungal agents derived from plants.

    PubMed

    Arif, Tasleem; Bhosale, J D; Kumar, Naresh; Mandal, T K; Bendre, R S; Lavekar, G S; Dabur, Rajesh

    2009-07-01

    A new spectrum of human fungal infections is increasing due to increased cancer, AIDS, and immunocompromised patients. The increased use of antifungal agents also resulted in the development of resistance to the present drugs. It makes necessary to discover new classes of antifungal compounds to cure fungal infections. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, saponins, alkaloids, flavonoids, and other compounds, reported to have in vitro antifungal properties. Since the plant kingdom provides a useful source of lead compounds of novel structure, a wide-scale investigation of species from the tropics has been considered. Therefore, the research on natural products and compounds derived from natural products has accelerated in recent years due to their importance in drug discovery. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans. These molecules may be used directly or considered as a precursor for developing better molecules. This review attempts to summarize the current status of important antifungal compounds from plants. PMID:20183299

  20. Comparison of antifungal activities of Vietnamese citrus essential oils.

    PubMed

    Van Hung, Pham; Chi, Pham Thi Lan; Phi, Nguyen Thi Lan

    2013-03-01

    Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries. PMID:22799453

  1. Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis

    PubMed Central

    Boisard, Séverine; Le Ray, Anne-Marie; Landreau, Anne; Kempf, Marie; Cassisa, Viviane; Flurin, Catherine; Richomme, Pascal

    2015-01-01

    During this study, the in vitro antifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains including Staphylococcus aureus. Organic extracts showed a significant antifungal activity against C. albicans and C. glabrata (MIC80 between 16 and 31?µg/mL) but only a weak activity towards A. fumigatus (MIC80 = 250?µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially against S. aureus (SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100 30–97?µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study. PMID:25873978

  2. Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery

    PubMed Central

    Anastassopoulou, Cleo G.; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios

    2013-01-01

    The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-c. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future. PMID:21470110

  3. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    PubMed

    Breger, Julia; Fuchs, Beth Burgwyn; Aperis, George; Moy, Terence I; Ausubel, Frederick M; Mylonakis, Eleftherios

    2007-02-01

    There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi. PMID:17274686

  4. ALTERATIONS IN mRNA GENE EXPRESSION ASSOCIATED WITH CHOLESTEROL METABOLISM, CELL CYCLE, AND OXIDATIVE STRESS INDUCED BY TRIAZOLE CONTAINING CONAZOLES IN RAT LIVER

    EPA Science Inventory

    Conazoles are fungicides used as pharmaceuticals and in agriculture. Triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland. In contrast,propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. It was proposed that tri...

  5. Atmospheric pressure cold plasma as an antifungal therapy

    SciTech Connect

    Sun Peng; Wu Haiyan; Sun Yi; Liu Wei; Li Ruoyu; Zhu Weidong; Lopez, Jose L.; Zhang Jue; Fang Jing

    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.

  6. Impact of brief exposure to antifungal agents on the post-antifungal effect and hemolysin activity of oral Candida albicans.

    PubMed

    Ellepola, Arjuna Nishantha; Khajah, Rana; Jayatilake, Sumedha; Samaranayake, Lakshman; Sharma, Prem; Khan, Zia

    2015-08-01

    Post-antifungal effect (PAFE) of Candida and its production of hemolysin are determinants of candidal pathogenicity. Candida albicans is the foremost aetiological agent of oral candidosis, which can be treated with polyene, azole, and echinocandin antifungals. However, once administered, the intraoral concentrations of these drugs tend to be subtherapeutic and transient due to the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, Candidamay undergo a brief exposure to antifungal drugs.Objective Therefore, the PAFE and hemolysin production of oral C. albicans isolates following brief exposure to sublethal concentrations of the foregoing antifungals were evaluated.Material and Methods A total of 50 C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for 60 min. Thereafter, the drugs were removed and the PAFE and hemolysin production were determined by previously described turbidometric and plate assays, respectively.Results Nystatin, amphotericin B, caspofungin and ketoconazole induced mean PAFE (hours) of 2.2, 2.18, 2.2 and 0.62, respectively. Fluconazole failed to produce a PAFE. Hemolysin production of these isolates was suppressed with a percentage reduction of 12.27, 13.47, 13.33, 8.53 and 4.93 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole, respectively.Conclusions Brief exposure to sublethal concentrations of antifungal drugs appears to exert an antifungal effect by interfering with the growth as well as hemolysin production of C. albicans. PMID:26398514

  7. Identification and biological activity of antifungal saponins from shallot ( Allium cepa L. Aggregatum group).

    PubMed

    Teshima, Yoshiki; Ikeda, Tsuyoshi; Imada, Kiyoshi; Sasaki, Kazunori; El-Sayed, Magdi A; Shigyo, Masayoshi; Tanaka, Shuhei; Ito, Shin-Ichi

    2013-08-01

    The n-butanol extract of shallot basal plates and roots showed antifungal activity against plant pathogenic fungi. The purified compounds from the extract were examined for antifungal activity to determine the predominant antifungal compounds in the extract. Two major antifungal compounds purified were determined to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal activity against a wide range of fungi. The products of acid hydrolysis of ALA showed a reduced antifungal activity, suggesting that the compound's sugar chain is essential for its antifungal activity. Fungal cells treated with ALA showed rapid production of reactive oxygen species. The fungicidal action of ALA was partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide anion generation in the fungal cells may be related to the compound's action. Inoculation experiments showed that ALA protected strawberry plants against Colletotrichum gloeosporioides , indicating that ALA has the potential to control anthracnose of the plant. PMID:24138065

  8. Antifungal activity of heartwood extracts from three Juniperus species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heartwood samples from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane, ethanol and methanol and the hexane and ethanol extracts were tested for antifungal activity against four species of wood-rot fungi. These three species represent the ...

  9. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

    Pa?kowski, ?ukasz; B?aszczy?ski, Jerzy; Skrzypczak, Andrzej; B?aszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Ko?uszko, Sylwia; Gospodarek, Eugenia; S?owi?ski, Roman; Krysi?ski, Jerzy

    2015-01-01

    The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds. PMID:25961015

  10. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... percent. (e) Tolnaftate 1 percent. (f) Undecylenic acid, calcium undecylenate, copper undecylenate,...

  11. Enhancement of commercial antifungal agents by kojic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay

    E-print Network

    Ausubel, Frederick M.

    of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows

  13. Chemosensitization as a means to augment commercial antifungal agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is growing list of papers on antimycotic chemosensitization and the mechanisms by which they function. Currently, antifungal agents used in agriculture and in human or veterinary medicine are confronted by a number of obstacles, the main one being continual development of resistance to one, or...

  14. The bacteriome-mycobiome interaction and antifungal host defense.

    PubMed

    Oever, Jaap Ten; Netea, Mihai G

    2014-11-01

    Large communities of microorganisms, collectively termed the microbiome, inhabit our body surfaces. With the advent of next-generation sequencing, the diversity and abundance of these communities are being unravelled. Besides an imporant role in metabolic processes, the microbiome is essential for proper functioning of our immune system, including the defense against fungi. Despite the progress of the past years, studies aimed at characterizing our fungal colonizers (the mycobiome) are limited; nevertheless fungi are important players of the microbiome, either as a cofactor in disease or as potential pathogens. In this review, we describe the role of the bacterial microbiome in antifungal host defense. On the one hand, bacteria provide colonization resistance to fungi, inhibit Candida virulence by preventing yeast-hyphal transition and contribute to epithelial integrity, all factors are important for the pathogenesis of invasive fungal disease. On the other hand, several bacterial species modulate mucosal (antifungal) immune responses. Murine studies demonstrate important effects of the microbiome on the antifungal responses of T-helper 17 cells, regulatory T cells and innate lymphoid cells. Inferred from these studies, perturbation of the healthy microbiome should be avoided and microbiome manipulation and interventions based on bacteria-derived pathways involved in immunomodulation are attractive options for modulating antifungal host defense. PMID:25256886

  15. In Vitro Screening of 10 Edible Thai Plants for Potential Antifungal Properties

    PubMed Central

    Luplertlop, Natthanej

    2014-01-01

    Growing rates of fungal infections and increasing resistance against standard antifungal drugs can cause serious health problems. There is, therefore, increasing interest in the potential use of medicinal plants as novel antifungal agents. This study investigates the antifungal properties of crude plant extracts from ten medicinal plant species. Crude samples were extracted using the hot water extraction process. The minimum inhibitory concentrations (MIC) and diameter zone of inhibition were determined in each extract against ten fungal strains, and fluconazole was used as a positive control. The cytotoxicity of crude extracts on in vitro human skin fibroblast (HSF) cell models was determined by MTT assay. Of the ten crude extracts, Psidium guajava L. exhibited the highest antifungal activity, diameter zone of inhibition, and percentage HSF cell viability. Although all extracts exhibited antifungal activity, Psidium guajava L. had the greatest potential for developing antifungal treatments. PMID:24516502

  16. Synthesis of heterocycle-attached methylidenebenzenesulfonohydrazones as antifungal agents.

    PubMed

    Gao, Zhinan; Lv, Min; Li, Qin; Xu, Hui

    2015-11-15

    A series of heterocycle-attached methylidenebenzenesulfonohydrazone derivatives were synthesized and evaluated for their antifungal activities against seven phytopathogenic fungi such as Fusarium graminearum, Alternaria solani, Valsa mali, Phytophthora capsici, Fusarium solani, Botrytis cinerea, and Glomerella cingulata. Compounds 7b, 8d, 9a, 9b and 9d exhibited a good and broad-spectrum of antifungal activities against at least five phytopathogenic fungi at the concentration of 100?g/mL. It demonstrated that addition of one double bond between the phenylsulfonylhydrazone fragment and the furan ring of 6a,b,d could afford more active compounds 9a,b,d; however, introduction of the nitro group on the phenyl ring of 6a-9a gave less potent compounds 6e-9e. PMID:26471091

  17. Trichoharzianol, a new antifungal from Trichoderma harzianum F031.

    PubMed

    Jeerapong, Chotika; Phupong, Worrapong; Bangrak, Phuwadol; Intana, Warin; Tuchinda, Patoomratana

    2015-04-15

    A new decalin derivative, trichoharzianol (1), together with three known compounds, eujavanicol A (2), 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (3), and 4,6-dihydroxy-5-methylphthalide (4), were isolated from Trichoderma harzianum F031. For the first time, compounds 2-4 were reported from the Trichoderma species. Their structures were characterized by spectroscopic methods. Trichoharzianol (1) showed the highest antifungal activity against Colletotrichum gloeosporioides, with a minimum inhibitory concentration (MIC) of 128 ?g/mL. PMID:25817439

  18. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

    PubMed Central

    Shrestha, Sanjib K.; Chang, Cheng-Wei T.; Meissner, Nicole; Oblad, John; Shrestha, Jaya P.; Sorensen, Kevin N.; Grilley, Michelle M.; Takemoto, Jon Y.

    2014-01-01

    K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20?s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate (FITC), 20–25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30–80% in 15 min) of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications. PMID:25538692

  19. Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia?

    PubMed Central

    Alastruey-Izquierdo, Ana; Cuesta, Isabel; Walther, Grit; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

    2010-01-01

    Forty-four isolates belonging to human pathogenic species of Lichtheimia were tested against nine antifungal agents by using the EUCAST methodology. No remarkable differences were found between the clinical species, although L. ramosa showed slightly higher MICs for all drugs. Amphotericin B was the most active drug. Among azole drugs, posaconazole had the best activity in vitro and voriconazole was inactive. Echinocandins showed activity for some isolates, suggesting a potential role in combination therapy. PMID:20421405

  20. Antifungal Activity of Ellagic Acid In Vitro and In Vivo.

    PubMed

    Li, Zhi-Jian; Guo, Xin; Dawuti, Gulina; Aibai, Silafu

    2015-07-01

    Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti-inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38-A and M27-A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33?µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0?µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC?=?18.75?µg/ml). Studies on the mechanism of action using an HPLC-based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14?-demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0?mg/cm(2) ) significantly enhanced the cure rate in a guinea-pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. PMID:25919446

  1. Antifungal susceptibilities of dermatophytic agents isolated from clinical specimens.

    PubMed

    Cetinkaya, Zafer; Kiraz, Nuri; Karaca, Semsettin; Kulac, Mustafa; Ciftci, Ihsan H; Aktepe, Orhan C; Altindis, Mustafa; Kiyildi, Nilay; Piyade, Meltem

    2005-01-01

    The aim of this study was to investigate the susceptibility to four antifungal agents: ketoconazole, terbinafine, itraconazole and fluconazole, of the different species of dermatophyte strains isolated from clinical specimens. A total of 128 specimens were collected from toe nail, foot, inguinal region, trunk, hands and head. The dermatophytes tested included Trichophyton rubrum 108 (84.4%), Trichophyton mentagrophytes 11 (8.6%), Epidermophyton floccosum 5 (3.9%), Microsporum canis 2 (1.5%) and Trichophyton tonsurans 2 (1.5%). The mean minimum inhibitory concentrations (MIC) for the five species of dermatophytes ranged between 0.09-1.12 microg/mL for ketoconazole, 0.04-0.27 microg/mL for terbinafine, 0.08-0.43 microg/mL for itraconazole and 16.18-24.0 microg/mL for fluconazole. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different systemic antifungals, which in turn may clarify the reasons for the lack of clinical response or serve as an effective therapy for patients with chronic infection. PMID:16048753

  2. New constitutive latex osmotin-like proteins lacking antifungal activity.

    PubMed

    Freitas, Cleverson D T; Silva, Maria Z R; Bruno-Moreno, Frederico; Monteiro-Moreira, Ana C O; Moreira, Renato A; Ramos, Márcio V

    2015-11-01

    Proteins that share similar primary sequences to the protein originally described in salt-stressed tobacco cells have been named osmotins. So far, only two osmotin-like proteins were purified and characterized of latex fluids. Osmotin from Carica papaya latex is an inducible protein lacking antifungal activity, whereas the Calotropis procera latex osmotin is a constitutive antifungal protein. To get additional insights into this subject, we investigated osmotins in latex fluids of five species. Two potential osmotin-like proteins in Cryptostegia grandiflora and Plumeria rubra latex were detected by immunological cross-reactivity with polyclonal antibodies produced against the C. procera latex osmotin (CpOsm) by ELISA, Dot Blot and Western Blot assays. Osmotin-like proteins were not detected in the latex of Thevetia peruviana, Himatanthus drasticus and healthy Carica papaya fruits. Later, the two new osmotin-like proteins were purified through immunoaffinity chromatography with anti-CpOsm immobilized antibodies. Worth noting the chromatographic efficiency allowed for the purification of the osmotin-like protein belonging to H. drasticus latex, which was not detectable by immunoassays. The identification of the purified proteins was confirmed after MS/MS analyses of their tryptic digests. It is concluded that the constitutive osmotin-like proteins reported here share structural similarities to CpOsm. However, unlike CpOsm, they did not exhibit antifungal activity against Fusarium solani and Colletotrichum gloeosporioides. These results suggest that osmotins of different latex sources may be involved in distinct physiological or defensive events. PMID:26231325

  3. Antifungal activities and chemical composition of some medicinal plants.

    PubMed

    Mohammadi, A; Nazari, H; Imani, S; Amrollahi, H

    2014-06-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists and natural-products scientists are combing the earth for phytochemicals and leads, which could be developed for treatment of infectious diseases. The aim of this study was to investigate the antifungal activities of the essential oils of some medicinal plants such as Stachys pubescens, Thymus kotschyanus, Thymus daenensis and Bupleurum falcatum against Fusarium oxysporum, Aspergillus flavus and Alternaria alternata. The essential oils were used to evaluate their MICs and MFCs compared to the amphotricin B as a standard drug. The essential oils were also analyzed by GC/MS. Essential oils isolated from the S. pubescens, T. kotschyanus and B. falcatum showed strong antifungal activities. The essential oil of T. daenensis exhibited a moderate activity against the selected fungi in comparison with the other plants' essential oils. In addition, the results showed that 26, 23, 22 and 15 components were identified from the essential oils of T. kotschyanus, S. pubescens, T. daenensis and B. falcatum, respectively. These oils exhibited a noticeable antifungal activity against the selected fungi. Regarding obtained results and that natural antimicrobial substances are inexpensive and have fewer side effects, they convey potential for implementation in fungal pathogenic systems. PMID:24768063

  4. Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings.

    PubMed

    Boehm, Ryan D; Daniels, Justin; Stafslien, Shane; Nasir, Adnan; Lefebvre, Joe; Narayan, Roger J

    2015-01-01

    In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius?=?25?±?3??m) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9?±?0.3?GPa) and hardness (588.2?±?33.8?MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions. PMID:25732934

  5. Pothomorphe umbellata: antifungal activity against strains of Trichophyton rubrum.

    PubMed

    Rodrigues, E R; Nogueira, N G P; Zocolo, G J; Leite, F S; Januario, A H; Fusco-Almeida, A M; Fachin, A L; de Marchi, M R R; dos Santos, A G; Pietro, R C L R

    2012-09-01

    Trichophyton rubrum is a dermatophyte, which can cause infections in human skin, hair and nail. Pothomorphe umbellata (L.) Miq. (Piperaceae) is a native Brazilian plant, in which phytochemical studies have demonstrated the presence of steroids, 4-nerolidylcatechol, sesquiterpenes and essential oils. The objective of this study was to analyze the in vitro activity of extracts and fractions of P. umbellata on resistant strains of T. rubrum. The microdilution plate method was utilized to test Tr1, H6 and ?TruMDR2 strains of T. rubrum; ?TruMDR2 strain was obtained from H6 by TruMDR2 gene rupture, which is involved in multiple drugs resistance. The highest antifungal activity to all strains was observed for dichloromethane and hexane fractions of the 70% ethanolic extract which showed minimal inhibitory concentration (MIC) and minimal fungicide concentration (MFC) of 78.13 ?g/mL. This antifungal activity was also obtained by 70% ethanolic extract, which presented MIC and MFC of 78.13 ?g/mL to ?TruMDR2, whereas the MIC values for Tr1 and H6 were 78.13 and 156.25 ?g/mL, respectively. Our results suggest the potential for future development of new antifungal drugs from P. umbellata, especially to strains presenting multiple resistance. PMID:23518086

  6. Antifungal defensins and their role in plant defense

    PubMed Central

    Lacerda, Ariane F.; Vasconcelos, Érico A. R.; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F.

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term “plant defensin,” after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 ?M and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  7. Antifungal defensins and their role in plant defense.

    PubMed

    Lacerda, Ariane F; Vasconcelos, Erico A R; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term "plant defensin," after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 ?M and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  8. Antifungal and cytotoxic activities of Nannorrhops ritchiana roots extract.

    PubMed

    Rashid, Rehana; Mukhtar, Farah; Khan, Abida

    2014-01-01

    This atudy was designed to evaluate the antifungal and cytotoxic activities of the Nannorrhops ritchiana (Mazari Palm) 80% methanol extract (NR-M) and its four crude extracts i.e., petroleum ether (NR-A), dichloromethane (NR-B), ethyl acetate (NR-C) and butanol (NR-D). The antifungal activity was determined by agar tube dilution method against nine fungal strains; Aspergillus flavus, Trichophyton longifusis, Trichophyton mentagrophytes, Aspergillus flavus and Microsporum canis were susceptible to the extracts with percentage inhibition of (70-80%). Extracts exhibited significant and good antifungal activity against various fungal strains. The results were deduced by comparing with those for miconazole, amphotericin B and ketoconazole as standard drugs. The fractions of methanolic extract were assayed for their brine shrimp cytotoxic activity. They exhibited low toxicity with LC50 values ranging from 285.7 to 4350.75 ?g/mL at the concentration of obtained results warrant follow up through bioassay guided isolation of the active principles, future antiinfectious research. PMID:25362807

  9. Phylogenetic Relationships Matter: Antifungal Susceptibility among Clinically Relevant Yeasts

    PubMed Central

    Schmalreck, A. F.; Becker, K.; Fegeler, W.; Czaika, V.; Ulmer, H.; Lass-Flörl, C.

    2014-01-01

    The objective of this study was 2-fold: to evaluate whether phylogenetically closely related yeasts share common antifungal susceptibility profiles (ASPs) and whether these ASPs can be predicted from phylogeny. To address this question, 9,627 yeast strains were collected and tested for their antifungal susceptibility. Isolates were reidentified by considering recent changes in taxonomy and nomenclature. A phylogenetic (PHYLO) code based on the results of multilocus sequence analyses (large-subunit rRNA, small-subunit rRNA, translation elongation factor 1?, RNA polymerase II subunits 1 and 2) and the classification of the cellular neutral sugar composition of coenzyme Q and 18S ribosomal DNA was created to group related yeasts into PHYLO groups. The ASPs were determined for fluconazole, itraconazole, and voriconazole in each PHYLO group. The majority (95%) of the yeast strains were Ascomycetes. After reclassification, a total of 23 genera and 54 species were identified, resulting in an increase of 64% of genera and a decrease of 5% of species compared with the initial identification. These taxa were assigned to 17 distinct PHYLO groups (Ascomycota, n = 13; Basidiomycota, n = 4). ASPs for azoles were similar among members of the same PHYLO group and different between the various PHYLO groups. Yeast phylogeny may be an additional tool to significantly enhance the assessment of MIC values and to predict antifungal susceptibility, thereby more rapidly initiating appropriate patient management. PMID:24366735

  10. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13mg/ml and 1mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13mg/ml and 4mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry. PMID:26593505

  11. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

  12. Antifungal activity of antifungal drugs, as well as drug combinations against Exophiala dermatitidis.

    PubMed

    Sun, Yi; Liu, Wei; Wan, Zhe; Wang, Xiaohong; Li, Ruoyu

    2011-02-01

    To evaluate the in vitro efficacy of common antifungal drugs, as well as the interactions of caspofungin with voriconazole, amphotericin B, or itraconazole against the pathogenic black yeast Exophiala dermatitidis from China, the minimal inhibitory concentrations (MICs) of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against 16 strains of E. dermatitidis were determined by using CLSI broth microdilution method (M38-A2). The minimal fungicidal concentrations (MFCs) were also determined. Additionally, the interactions of caspofungin with voriconazole, amphotericin B, itraconazole or fluconazole, that of terbinafine with itraconazole, or that of fluconazole with amphotericin B were assessed by using the checkerboard technique. The fractional inhibitory concentration index (FICI) was used to categorize drug interactions as following, synergy, FICI ? 0.5; indifference, FICI > 0.5 and ?4.0; or antagonism, FICI > 4.0. The MIC ranges of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against E. dermatitidis were 0.06-0.125 mg/l, 0.25-1.0 mg/l, 1.0-2.0 mg/l, 1.0-2.0 mg/l, 16-64 mg/l, and 32-64 mg/l, respectively. The in vitro interactions of caspofungin with voriconazole, amphotericin B, and itraconazole showed synergic effect against 10/16(62.5%), 15/16(93.75%), and 16/16(100%) isolates, while that of caspofungin with fluconazole showed indifference. Besides, the interaction of terbinafine with itraconazole as well as that of fluconazole with amphotericin B showed indifference. Terbinafine, voriconazole, itraconazole, and amphotericin B have good activity against E. dermatitidis. The combinations of caspofungin with voriconazole, amphotericin B or itraconazole present synergic activity against E. dermatitidis. These results provide the basis for novel options in treating various E. dermatitidis infections. PMID:20803255

  13. The search for antifungals from Amazonian trees: a bio-inspired screening.

    PubMed

    Basseta, Charlie; Eparvier, Véronique; Espindolab, Laila S

    2015-04-01

    The anti-fungal activity of 60 extracts from 15 tree species in the French Guiana rainforest against human and wood-rotting fungi was studied. In this way (+)-mopanol (1) was isolated from the ethyl acetate extract of Peltogyne sp. (Caesalpiniaceae) wood. This work demonstrated that (1) the natural durability of wood can indeed guide the search for antifungal agents, (2) that extracts selected in this bio-inspired process exhibit a broad spectrum of antifungal activity and (3) that the method allows for the isolation of strongly active antifungals. PMID:25973487

  14. Study of the antifungal activity of Acinetobacter baumannii LCH001 in vitro and identification of its antifungal components.

    PubMed

    Liu, C H; Chen, X; Liu, T T; Lian, B; Gu, Yucheng; Caer, V; Xue, Y R; Wang, B T

    2007-08-01

    An Acinetobacter strain, given the code name LCH001 and having the potential to be an endophytic antagonist, has been isolated from healthy stems of the plant Cinnamomum camphora (L.) Presl, guided by an in vitro screening technique. The bacterium inhibited the growth of several phytopathogenic fungi such as Cryphonectria parasitica, Glomerella glycines, Phytophthora capsici, Fusarium graminearum, Botrytis cinerea, and Rhizoctonia solani. Biochemical, physiological, and 16S rDNA sequence analysis proved that it is Acinetobacter baumannii. When the filtrate from the fermentation broth of strain LCH001 was tested in vitro and in vivo, it showed strong growth inhibition against several phytopathogens including P. capsici, F. graminearum, and R. solani, indicating that suppression of the growth of the fungi was due to the presence of antifungal compounds in the culture broth. Moreover, the antifungal activity of the culture filtrate was significantly correlated with the cell growth of strain LCH001. The active metabolites in the filtrate were relatively thermally stable, but were sensitive to acidic conditions. Three antifungal compounds were isolated from the culture broth by absorption onto macropore resin, ethanol extraction, chromatography on silica gel or LH-20 columns, and crystallization. The structures of the bioactive compounds were identified by spectroscopic methods as isomers of iturin A, namely, iturin A2, iturin A3, and iturin A6. The characterization of an unusual endophytic bacterial strain LCH001 and its bioactive components may provide an alternative resource for the biocontrol of plant diseases. PMID:17534613

  15. Optimization of Spore and Antifungal Lipopeptide Production during the Solid State Fermentation of Bacillus subtilis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus subtilis strain TrigoCor 1448 was grown on wheat middlings in 0.5-liter solid state fermentation (SSF) bioreactors for the production of an antifungal biological control agent. Total antifungal activity was quantified using a 96-well microplate bioassay against the plant pathogen Fusarium ...

  16. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrazone derivatives possess good antifungal and insecticidal activities and their structure are used in pesticide design. In the present study, ten hydrazone derivatives (2a-j) were evaluated for their antifungal activity against Colletotrichum, Botrytis, Fusarium and Phomopsis species and for the...

  17. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant ...

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

    PubMed Central

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

    2008-01-01

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

  20. Suppressive Drug Interactions between Antifungals Marjon G.J. de Vos1 and Tobias Bollenbach1,*

    E-print Network

    Suppressive Drug Interactions between Antifungals Marjon G.J. de Vos1 and Tobias Bollenbach1,* 1IST a systematic study of drug interactions be- tween antifungal compounds. Suppressive drug interactions occur. When two drugs are combined, they may interact synergistically or antago- nistically; for synergistic

  1. Antifungal activity of gold nanoparticles prepared by solvothermal method

    SciTech Connect

    Ahmad, Tokeer; Wani, Irshad A.; Lone, Irfan H.; Ganguly, Aparna; Manzoor, Nikhat; Ahmad, Aijaz; Ahmed, Jahangeer; Al-Shihri, Ayed S.

    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: 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.

  2. Evaluation of antifungal susceptibility testing in Candida isolates by Candifast and disk-diffusion method.

    PubMed

    Giri, Sidhartha; Kindo, Anupma Jyoti

    2014-01-01

    With the increase in invasive fungal infections due to Candida species and resistance to antifungal therapy, in vitro antifungal susceptibility testing is becoming an important part of clinical microbiology laboratories. Along with broth microdilution and disk diffusion method, various commercial methods are being increasingly used for antifungal susceptibility testing, especially in the developed world. In our study, we compared the antifungal susceptibility patterns of 39 isolates of Candida to three antifungal drugs (fluconazole, amphotericin B, ketoconazole) by Candifast and disk diffusion method. The following resistance pattern was found by Candifast: Fluconazole (30.8%), ketoconazole (12.8%), amphotericin B (0%). The results obtained by disk diffusion method were in complete agreement with Candifast results. PMID:25308014

  3. Antifungal activity of essential oils from leaves and flowers of Inula viscosa (Asteraceae) by Apulian region.

    PubMed

    Cafarchia, C; De Laurentis, N; Milillo, M A; Losacco, V; Puccini, V

    2002-12-01

    Some essential oils from several plants (Artemisia verlotorum, Lavandula augustifolia, Ocimum gratissimum) have proved to have acaricidal, antifungal and antibacterial activity. Inula viscosa Ait. (Asteraceae), a plant growing spontaneously in the Mediterranean area, is currently used by popular medicine for its therapeutic effects. Flavonoids, azulenes, sesquiterpenes, and essential oils have been isolated and identified from its leaves. This paper reports the results of the composition and antifungal activity in vitro against dermatophytes and Candida spp. of the four essential oils obtained by steam distillation of the leaves, flowers, whole plant and whole plants without flower extracts of I. viscosa. All the extracts proved to have a significant antifungal activity against dermatophytes even at low concentrations (0.01 mg/ml). The leaf extracts exhibited the greatest antifungal efficacy. The high concentration of the sesquiterpene (carboxyeudesmadiene), occurring in the leaf extracts, may explain its greater antifungal activity. PMID:12701377

  4. Mechanism of Action of Efinaconazole, a Novel Triazole Antifungal Agent

    PubMed Central

    Nagashima, Maria; Shibanushi, Toshiyuki; Iwata, Atsushi; Kangawa, Yumi; Inui, Fumie; Siu, William J. Jo; Pillai, Radhakrishnan; Nishiyama, Yayoi

    2013-01-01

    The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4?-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14?-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

  5. Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.

    PubMed

    Asner, Sandra A; Giulieri, Stefano; Diezi, Manuel; Marchetti, Oscar; Sanglard, Dominique

    2015-12-01

    Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [?g/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [?g/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [?g/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [?g/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [?g/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy. PMID:26438490

  6. Antifungal activity of Lactobacillus against Microsporum canis, Microsporum gypseum and Epidermophyton floccosum

    PubMed Central

    Guo, Jiahui; Brosnan, Brid; Furey, Ambrose; Arendt, Elke; Murphy, Padraigin; Coffey, Aidan

    2012-01-01

    A total of 220 lactic acid bacteria isolates were screened for antifungal activity using Aspergillus fumigatus and Aspergillus niger as the target strains. Four Lactobacillus strains exhibited strong inhibitory activity on agar surfaces. All four were also identified as having strong inhibitory activity against the human pathogenic fungi Microsporum canis, Microsporum gypseum and Epidermophyton floccosum. One of the four lactobacilli, namely Lb. reuteri ee1p exhibited the most inhibition against dermatophytes. Cell-free culture supernatants of Lb. reuteri ee1p and of the non-antifungal Lb. reuteri M13 were freeze-dried and used to access and compare antifungal activity in agar plate assays and microtiter plate assays. Addition of the Lb. reuteri ee1p freeze-dried cell-free supernatant powder into the agar medium at concentrations greater than 2% inhibited all fungal colony growth. Addition of the powder at 5% to liquid cultures caused complete inhibition of fungal growth on the basis of turbidity. Freeze-dried supernatant of the non-antifungal Lb. reuteri M13 at the same concentrations had a much lesser effect. As Lb. reuteri M13 is very similar to the antifungal strain ee1p in terms of growth rate and final pH in liquid culture, and as it has little antifungal activity, it is clear that other antifungal compounds must be specifically produced (or produced at higher levels) by the anti-dermatophyte strain Lb. reuteri ee1p. Reuterin was undetectable in all four antifungal strains. The cell free supernatant of Lb. reuteri ee1p was analyzed by LC-FTMS using an Accela LC coupled to an LTQ Orbitrap XL mass spectrometer. The high mass accuracy spectrum produced by compounds in the Lb. reuteri ee1p strain was compared with both a multianalyte chromatogram and individual spectra of standard anti-fungal compounds, which are known to be produced by lactic acid bacteria. Ten antifungal metabolites were detected. PMID:22539027

  7. Quantitative and qualitative analysis of the antifungal activity of allicin alone and in combination with antifungal drugs.

    PubMed

    Kim, Young-Sun; Kim, Kyung Sook; Han, Ihn; Kim, Mi-Hyun; Jung, Min Hyung; Park, Hun-Kuk

    2012-01-01

    The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy. PMID:22679493

  8. Quantitative and Qualitative Analysis of the Antifungal Activity of Allicin Alone and in Combination with Antifungal Drugs

    PubMed Central

    Han, Ihn; Kim, Mi-Hyun; Jung, Min Hyung; Park, Hun-Kuk

    2012-01-01

    The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy. PMID:22679493

  9. Comparison of an antifungal agent used alone with an antifungal used with a topical steroid in inflammatory tinea pedis.

    PubMed

    Elewski, B E; Jones, T; Zaias, N

    1996-10-01

    The efficacy and safety of monotherapy with oxiconazole nitrate cream, 1 percent, a topical broadspectrum antifungal agent, were compared with those of combination therapy with oxiconazole nitrate cream, 1 percent, and fluticasone propionate cream, 0.05 percent, in a multicenter, randomized, double-blind, vehicle-controlled, parallel-group study of patients with inflammatory tinea pedis. Both combination therapy and monotherapy were associated with significantly greater proportions of mycologic and clinical cure, and a better global response than vehicle. An unexpected finding in this study was that more than 70 percent of patients with interdigital tinea pedis also had plantar or plantar plus vesiculobullous infection. PMID:8894432

  10. The Regulatory Pathway for Antifungal Drugs: A US Perspective.

    PubMed

    Tillotson, Joni; Tillotson, Glenn S

    2015-12-01

    Although there was a flurry of new antifungal drugs approved in the early part of the last decade, the growing need for newer agents to treat systemic fungal infections has escalated due to increasing resistance to the 2 main classes of drugs developed to date and shifts in the etiology of these diseases. In addition to this microbial shift, there are more at-risk patients who are being managed in increasingly heroic ways and are thus highly susceptible to these more common resistant fungi and yeasts. However, as we acknowledge the need for new drugs to treat these desperately ill patients, there is a basic problem facing the pharmaceutical industry as it tries to balance the conundrum of antifungal development. Globally there is a relatively low, but growing, number of systemic fungal infections, which creates significant hurdles in conducting clinical trials in a timely and economical manner. In the United States, there have been some significant moves to easing these hurdles and, potentially, to bringing new drugs to the clinic more quickly and efficiently. We will discuss the current unmet clinical need and the current US regulatory positions to encourage further investment in this critical field. PMID:26567287

  11. A novel antifungal protein of Bacillus subtilis B25.

    PubMed

    Tan, Zhiqiong; Lin, Baoying; Zhang, Rongyi

    2013-01-01

    Bacillus subtilis B25 was isolated from banana rhizosphere soil. It has been confirmed for B25 to have stronger antagonism against Fusarium oxysporum f.sp.cubense, Additionally B25 has good inhibitory to plant pathogens, including Corynespora cassiicola, Alternaria solani, Botrytis cinerea and Colletotrichum gloeosporioides on potato dextrose agar (PDA) plates. The antagonistic substance can be extracted from cell-free culture broth supernatants by 70% (w/v) (NH4)2 SO4 saturation. Clear blank band was observed between the protein and a pathogen. The examination of antagonistic mechanism under light microscope showed that the antifungal protein of B25 appeared to inhibit pathogens by leading to mycelium and spores tumescence, distortion, abnormality. The isolation procedure comprised ion exchange chromatography on DEAE-Sephadex Fast Flow and gel filtration chromatography on SephadexG-100. The purified antifungal fraction showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The active fraction was identified by NanoLC-ESI-MS/MS The amino acid sequences of 17 peptides segments were obtained. The analysis of the protein suggested that it was a hypothetical protein (gi154685475), with a relative molecular mass of 38708.67 Da and isoelectric point (pI) of 5.63. PMID:24255843

  12. Antifungal activity of chitooligosaccharides against the dermatophyte Trichophyton rubrum.

    PubMed

    Mei, Yu-xia; Dai, Xing-yi; Yang, Wei; Xu, Xiong-wei; Liang, Yun-xiang

    2015-06-01

    Antifungal activity against the dermatophytic fungus Trichophyton rubrum by a well-characterized chitooligosaccharides (COS) sample, hydrolyzed using a recombinant chitosanase, was investigated in vitro and in vivo. The minimum inhibitory concentration (MIC) of COS ranged between 0.25 and 0.50%, which was measured using a microdilution method. Analysis of inhibition rates using an agar diffusion method showed that treatment with 0.5% and 1% COS significantly suppressed T. rubrum cell growth (p<0.05 and p<0.01, respectively, in comparison with untreated control). Morphological changes and structural alterations of cells were observed by TEM. In vivo efficacy of COS in treatment of T. rubrum dermatophytosis was evaluated using a guinea pig model. Skin lesion scores revealed a strong, dose-dependent therapeutic effect of COS. The 5% COS group showed a reduction of skin lesions even greater than that of the positive control group treated with 1% fluconazole (FCZ). Histological analysis revealed no inflammation or tissue destruction in the groups treated with 5% COS or 1% FCZ. Hyperkeratosis was also observed, perhaps resulting from a defensive response of the tissue cells to COS. The findings indicate that COS has excellent potential for development of novel antifungal drugs for clinical treatment/remission of dermatophytoses. PMID:25841377

  13. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    SciTech Connect

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  14. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    PubMed

    Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

    2012-01-01

    This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in phosphoglycerides (PGLs) composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

  15. Antifungal properties of Canavalia ensiformis urease and derived peptides.

    PubMed

    Postal, Melissa; Martinelli, Anne H S; Becker-Ritt, Arlete B; Ligabue-Braun, Rodrigo; Demartini, Diogo R; Ribeiro, Suzanna F F; Pasquali, Giancarlo; Gomes, Valdirene M; Carlini, Celia R

    2012-11-01

    Ureases (EC 3.5.1.5) are metalloenzymes that hydrolyze urea into ammonia and CO(2). These proteins have insecticidal and fungicidal effects not related to their enzymatic activity. The insecticidal activity of urease is mostly dependent on the release of internal peptides after hydrolysis by insect digestive cathepsins. Jaburetox is a recombinant version of one of these peptides, expressed in Escherichia coli. The antifungal activity of ureases in filamentous fungi occurs at submicromolar doses, with damage to the cell membranes. Here we evaluated the toxic effect of Canavalia ensiformis urease (JBU) on different yeast species and carried out studies aiming to identify antifungal domain(s) of JBU. Data showed that toxicity of JBU varied according to the genus and species of yeasts, causing inhibition of proliferation, induction of morphological alterations with formation of pseudohyphae, changes in the transport of H(+) and carbohydrate metabolism, and permeabilization of membranes, which eventually lead to cell death. Hydrolysis of JBU with papain resulted in fungitoxic peptides (~10 kDa), which analyzed by mass spectrometry, revealed the presence of a fragment containing the N-terminal sequence of the entomotoxic peptide Jaburetox. Tests with Jaburetox on yeasts and filamentous fungi indicated a fungitoxic activity similar to ureases. Plant ureases, such as JBU, and its derived peptides, may represent a new alternative to control medically important mycoses as well as phytopathogenic fungi, especially considering their potent activity in the range of 10(-6)-10(-7)M. PMID:22922160

  16. Antifungal properties of new series of quinoline derivatives.

    PubMed

    Musiol, Robert; Jampilek, Josef; Buchta, Vladimir; Silva, Luis; Niedbala, Halina; Podeszwa, Barbara; Palka, Anna; Majerz-Maniecka, Katarzyna; Oleksyn, Barbara; Polanski, Jaroslaw

    2006-05-15

    The series of quinoline derivatives were prepared. The synthetic approach, analytical, and spectroscopic data of all synthesized compounds are presented. All the prepared derivatives were analyzed using the reversed-phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. In the present study, the correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and various calculated log P data is shown. The relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well. The prepared compounds were tested for their in vitro antifungal activity. 2-[(3-Hydroxyphenylimino)methyl]quinolin-8-ol (8), 2-[(4-hydroxyphenylimino)methyl]quinolin-8-ol (9) and 2-[(2,5-dichloro-4-nitrophenylamino)methoxymethyl]quinolin-8-ol (10) showed in vitro antifungal activity comparable to or higher than that of the standard fluconazole. Structure-activity relationships among the chemical structure, the physical properties, and the biological activities of the evaluated compounds are discussed in the article. PMID:16458522

  17. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.

    PubMed

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L; Avery, Simon V

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ?8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  18. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity

    PubMed Central

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L.; Avery, Simon V.

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ?8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  19. Contribution of volatiles to the antifungal effect of Lactobacillus paracasei in defined medium and yogurt.

    PubMed

    Aunsbjerg, S D; Honoré, A H; Marcussen, J; Ebrahimi, P; Vogensen, F K; Benfeldt, C; Skov, T; Knřchel, S

    2015-02-01

    Lactic acid bacteria with antifungal properties can be used to control spoilage of food and feed. Previously, most of the identified metabolites have been isolated from cell-free fermentate of lactic acid bacteria with methods suboptimal for detecting possible contribution from volatiles to the antifungal activity. The role of volatile compounds in the antifungal activity of Lactobacillus paracasei DGCC 2132 in a chemically defined interaction medium (CDIM) and yogurt was therefore investigated with a sampling technique minimizing volatile loss. Diacetyl was identified as the major volatile produced by L. paracasei DGCC 2132 in CDIM. When the strain was added to a yogurt medium diacetyl as well as other volatiles also increased but the metabolome was more complex. Removal of L. paracasei DGCC 2132 cells from CDIM fermentate resulted in loss of both volatiles, including diacetyl, and the antifungal activity towards two strains of Penicillium spp. When adding diacetyl to CDIM or yogurt without L. paracasei DGCC 2132, marked inhibition was observed. Besides diacetyl, the antifungal properties of acetoin were examined, but no antifungal activity was observed. Overall, the results demonstrate the contribution of diacetyl in the antifungal effect of L. paracasei DGCC 2132 and indicate that the importance of volatiles may have been previously underestimated. PMID:25461608

  20. Antifungal Susceptibility Profiles of 1698 Yeast Reference Strains Revealing Potential Emerging Human Pathogens

    PubMed Central

    Desnos-Ollivier, Marie; Robert, Vincent; Raoux-Barbot, Dorothée; Groenewald, Marizeth; Dromer, Françoise

    2012-01-01

    New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites) were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes). Interestingly, geometric mean minimum inhibitory concentrations (MICs) of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001). Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically “resistant” to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens. PMID:22396754

  1. Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.

    PubMed Central

    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

  2. In Vitro Activities of 10 Antifungal Drugs against 508 Dermatophyte Strains

    PubMed Central

    Fernández-Torres, B.; Carrillo, A. J.; Martín, E.; Del Palacio, A.; Moore, M. K.; Valverde, A.; Serrano, M.; Guarro, J.

    2001-01-01

    We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35°C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective. PMID:11502524

  3. Enhancement of the antifungal activity of antimicrobial drugs by Eugenia uniflora L.

    PubMed

    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. PMID:23819641

  4. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    PubMed Central

    Khedr, Mohammed A

    2015-01-01

    Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14?-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were synthesized and evaluated for their antifungal activity. In silico study results showed the high binding affinity to lanosterol 14?-demethylase (?24.49 and ?25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (?18.19 kcal/mol) and fluconazole (?16.08 kcal/mol). Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole. PMID:26309398

  5. ANTIFUNGAL ACTIVITY OF SILVER NANOPARTICLES OBTAINED BY GREEN SYNTHESIS

    PubMed Central

    MALLMANN, Eduardo José J.; CUNHA, Francisco Afrânio; CASTRO, Bruno N.M.F.; MACIEL, Auberson Martins; MENEZES, Everardo Albuquerque; FECHINE, Pierre Basílio Almeida

    2015-01-01

    Silver nanoparticles (AgNPs) are metal structures at the nanoscale. AgNPs have exhibited antimicrobial activities against fungi and bacteria; however synthesis of AgNPs can generate toxic waste during the reaction process. Accordingly, new routes using non-toxic compounds have been researched. The proposal of the present study was to synthesize AgNPs using ribose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer. The antifungal activity of these particles against C. albicans and C. tropicalis was also evaluated. Stable nanoparticles 12.5 ± 4.9 nm (mean ± SD) in size were obtained, which showed high activity against Candida spp. and could represent an alternative for fungal infection treatment. PMID:25923897

  6. Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

    PubMed Central

    Rex, John H.; Pfaller, Michael A.; Walsh, Thomas J.; Chaturvedi, Vishnu; Espinel-Ingroff, Ana; Ghannoum, Mahmoud A.; Gosey, Linda L.; Odds, Frank C.; Rinaldi, Michael G.; Sheehan, Daniel J.; Warnock, David W.

    2001-01-01

    Development of standardized antifungal susceptibility testing methods has been the focus of intensive research for the last 15 years. Reference methods for yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of these methods provides researchers not only with standardized methods for testing but also with an understanding of the variables that affect interlaboratory reproducibility. With this knowledge, we have now moved into the phase of (i) demonstrating the clinical value (or lack thereof) of standardized methods, (ii) developing modifications to these reference methods that address specific problems, and (iii) developing reliable commercial test kits. Clinically relevant testing is now available for selected fungi and drugs: Candida spp. against fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B; Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful testing procedures is the current focus of research in this area. PMID:11585779

  7. Synthesis and antifungal activity of two novel spermidine analogues.

    PubMed

    Mackintosh, C A; Slater, L A; McClintock, C A; Walters, D R; Havis, N D; Robins, D J

    1997-03-01

    Two spermidine analogues were synthesised and examined for antifungal activity. Both compounds used as 1 mM post-inoculation sprays reduced infection of barley seedlings by the powdery mildew fungus, Erysiphe graminis f.sp. hordei, infection of broad bean seedlings by the rust fungus, Uromyces viciae-fabae, and infection of apple seedlings by the powdery mildew fungus, Podosphaera leucotricha. Since these fungal pathogens cannot be cultured axenically, the effects of the two spermidine analogues on mycelial growth in vitro, as well as preliminary investigations on polyamine biosynthesis, were undertaken using the oat stripe pathogen, Pyrenophora avenae. Although neither compound affected radial growth of the fungus on plates, both analogues reduced fungal biomass in liquid culture substantially. The two spermidine analogues, used at a concentration of 1 mM, had no significant effect on the conversion of labelled ornithine into polyamines in P. avenae. PMID:9066105

  8. Characterization of Chitosan Nanofiber Sheets for Antifungal Application

    PubMed Central

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young’s modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young’s modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046

  9. Characterization of Chitosan Nanofiber Sheets for Antifungal Application.

    PubMed

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young's modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young's modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046

  10. Antifungal properties of silver nanoparticles against indoor mould growth.

    PubMed

    Ogar, Anna; Tylko, Grzegorz; Turnau, Katarzyna

    2015-07-15

    The presence of moulds in indoor environments causes serious diseases and acute or chronic toxicological syndromes. In order to inhibit or prevent the growth of microorganisms on building materials, the disruption of their vital processes or the reduction of reproduction is required. The development of novel techniques that impair the growth of microorganisms on building materials is usually based on silver nanoparticles (AgNPs). It makes them an alternative to other biocides. AgNPs have proven antibacterial activity and became promising in relation to fungi. The aim of the study was to assess growth and morphology of mycelia of typical indoor fungal species: Penicillium brevicompactum, Aspergillus fumigatus, Cladosporium cladosporoides, Chaetomium globosum and Stachybotrys chartarum as well as Mortierella alpina, cultured on agar media. The antifungal activity of AgNPs was also tested in relation to C. globosum and S. chartarum grown on the surface of gypsum drywall. It was found that the presence of AgNPs in concentrations of 30-200mg/l significantly decreased the growth of fungi. However, in the case of M. alpina, AgNPs stimulated its growth. Moreover, strong changes in moulds morphology and colour were observed after administration of AgNPs. Parameters of conidiophores/sporangiophores varied depending on mould region and changed significantly after treatment with AgNPs. The experiments have shown antifungal properties of AgNPs against common indoor mould species. Their application to building materials could effectively protect indoor environments from mould development. However, consideration must be given to the fact that the growth of some fungal strains might be stimulated by AgNPs. PMID:25847174

  11. Antifungal activity of Curcuma longa grown in Thailand.

    PubMed

    Wuthi-udomlert, M; Grisanapan, W; Luanratana, O; Caichompoo, W

    2000-01-01

    Curcuma longa Linn. or turmeric (Zingiberaceae) is a medicinal plant widely used and cultivated in tropical regions. According to Thai traditional texts, fresh and dried rhizomes are used as peptic ulcer treatment, carminatives, wound treatment and anti-inflammatory agent. Using hydro distillation, 1.88% and 7.02% (v/w) volatile oils were extracted from fresh and dried rhizomes, respectively, and 6.95% (w/w)crude curcuminoids were extracted from dried rhizomes. Dried powder was extracted with 95% ethanol and yielded 29.52% (w/w) crude ethanol extract composed of curcumin (11.6%), demethoxycurcumin (10.32%) and bisdemethoxycurcumin (10.77%). These extracts were tested for antifungal activity by agar disc diffusion method against 29 clinical strains of dermatophytes. It was found that crude ethanol extract exhibited an inhibition zone range of 6.1 to 26.0 mm. There was no inhibition activity from crude curcuminoids while curcumin, demethoxycurcumin and bisdemethoxycutcumin gave different inhibition zone diameters ranging from 6.1 to 16.0 mm. Although antifungal activity of undiluted freshly distilled oil and 18-month-old oil revealed some differences, the inhibition zone diameters for both extracts varied within 26.1 to 46.0 mm. With 200 mg/ml ketoconazole, the activities of the standard agent were similar to the oil, both freshly distilled and 18-month-old, but were significantly different from those of curcuminoid compounds and crude ethanol extracts (p < 0.01). Turmeric oil was also tested for its minimum inhibitory concentration (MIC) by broth dilution method. The MICs of freshly distilled and 18-month-old oils were 7.8 and 7.2 mg/ml respectively. PMID:11414453

  12. A Comparative Study of Antifungal Activity of Endodontic Irrigants

    PubMed Central

    Mohammadi, Zahed; Asgary, Saeed

    2015-01-01

    Introduction: The purpose of this in vitro study was to assess the antifungal activity of final canal rinse with either three concentrations of sodium hypochlorite (NaOCl) (0.5, 2.6 and 6%), two concentrations of chlorhexidine (CHX) (2% and 0.2%), MTAD, Tetraclean, Hypoclean and Chlor-Xtra on Candida albicans (C. albicans) in a human tooth model. Methods and Materials: Two hundred and thirty five extracted human maxillary central and lateral incisors were used in this study. Teeth were randomly divided into nine test groups (n=25) and positive and a negative control groups (n=5). After cleaning and shaping, teeth were contaminated with C. albicans and incubated for 72 h. The irrigation solution in nine experimental groups included: 6% NaOCl, 2.6% NaOCl, 0.5% NaOCl, 2% CHX, 0.2% CHX, MTAD, Tetraclean, Hypoclean and Chlor-Xtra. After culturing on Sabouraud 4% dextrose agar, colony-forming units (CFU) were counted. Results: 6% NaOCl, 2% CHX and Chlor-Xtra were equally effective (P>0.05) and significantly superior to MTAD and Tetraclean (P<0.05). In addition, the effectiveness of Tetraclean and MTAD was significantly less than Hypoclean, NaOCl at all concentrations (6% 2.6% and 0.5%), MTAD and 0.2% CHX (P<0.05). Furthermore, Tetraclean was significantly more effective than MTAD (P<0.05). Conclusion: Antifungal activity of 6% NaOCl, Chlor-Xtra and 2% CHX was significantly greater than 2.6% NaOCl, 0.5% NaOCl, MTAD, 0.2% CHX and Tetraclean. PMID:25834602

  13. [In vitro antifungal activity of rilopirox, a new hydroxypyridone antimycotic agent].

    PubMed

    Harada, I; Mitsui, K; Uchida, K; Yamaguchi, H

    1997-02-01

    In vitro antifungal activities of rilopirox (RIL), a new topical hydroxypyridone antifungal agent, were studied against 7 species (31 strains) of yeast-like fungi and 15 species (17 strains) of mycerial fungi from stock cultures of a wide range of medically important fungi. Tests were carried out by the liquid dilution method using Neopeptone dextrose broth with ciclopirox olamine (CPO) and oxiconazole nitrate (OCZ) as reference drugs. RIL exhibited a broad spectrum of antifungal activities; the MIC of RIL against yeasts were about 1 microgram/ml, those against other fungi were 0.5-4 micrograms/ml. Antifungal activities were similar to CPO, and compare to OCZ, RIL showed characteristically little differences in its activities against different species or strains of target organisms. PMID:9100079

  14. A case of fungal keratitis caused by Scopulariopsis brevicaulis: treatment with antifungal agents and penetrating keratoplasty.

    PubMed Central

    Ragge, N K; Hart, J C; Easty, D L; Tyers, A G

    1990-01-01

    A case of fungal keratitis caused by Scopulariopsis brevicaulis following a penetrating eye injury is described. Treatment with antifungal agents and keratoplasty resulted in a favourable outcome. Images PMID:2168203

  15. In vitro antifungal activity of dihydroxyacetone against causative agents of dermatomycosis.

    PubMed

    Stopiglia, Cheila Denise Ottonelli; Vieira, Fabiane Jamono; Mondadori, Andressa Grazziotin; Oppe, Tércio Paschke; Scroferneker, Maria Lúcia

    2011-04-01

    Dihydroxyacetone (DHA), a three-carbon sugar, is the browning ingredient in commercial sunless tanning formulations. DHA preparations have been used for more than 50 years and are currently highly popular for producing temporary pigmentation resembling an ultraviolet-induced tan. In this work, the in vitro antifungal activity of dihydroxyacetone was tested against causative agents of dermatomycosis, more specifically against dermatophytes and Candida spp. The antifungal activity was determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines for yeasts and filamentous fungi. The data obtained show that the fungicidal activity varied from 1.6 to 50 mg ml(-1). DHA seems to be a promising substance for the treatment of dermatomycosis because it has antifungal properties at the same concentration used in artificial suntan lotions. Therefore, it is a potential low-toxicity antifungal agent that may be used topically because of its penetration into the corneal layers of the skin. PMID:20936361

  16. Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

    PubMed

    Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

    2007-06-27

    Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent. PMID:17542610

  17. Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability.

    PubMed

    Mahata, Denial; Mandal, Santi M; Bharti, Rashmi; Gupta, Vinay Krishna; Mandal, Mahitosh; Nag, Ahindra; Nando, Golok B

    2014-08-01

    Cardanol is a non-isoprenoic phenolic lipid-mixture of distilled cashew nut shell liquid obtained from Anacardium occidentale. Herein, cardanol is purified from cashew nut shell liquid (CNSL) and synthesized to new compounds with different azo amphiphiles. These synthesized compounds are allowed to self-assembled in hydrophobic environment and checked antifungal activity against Candida albicans. Self-assembled structure of CABA showed higher antifungal activity (16?g/mL) and chitin-binding ability in comparison to CAP and CANB. Furthermore, the self-assembled azo amphiphiles are immobilized with silver ions to prepare hydrogel which showed eight folds enhanced antifungal activity. Toxicity is reduced by several folds of self-assembled or hydrogel structure in comparison to pure compounds. Thus, the self-assembled structure of amphiphiles and their hydrogels have been found to be new macromolecules of interest with potential use as antifungal drugs. PMID:24836571

  18. Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals

    EPA Science Inventory

    The mode of action for the reproductive toxicity of triazole antifungals have been previously characterized by an observed increased in serum testosterone, hepatotoxicity, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these m...

  19. Purification and Identification of Two Antifungal Cyclic Peptides Produced by Bacillus amyloliquefaciens L-H15.

    PubMed

    Han, Yuzhu; Zhang, Bao; Shen, Qian; You, Chengzhen; Yu, Yaqiong; Li, Pinglan; Shang, Qingmao

    2015-08-01

    Bacillus amyloliquefaciens L-H15 with broad spectrum antifungal activity was used as a biocontrol agent to suppress Fusarium oxysporum and other soil-borne fungal plant pathogens. Two antifungal fractions were isolated by bioactivity-guided reversed-phase high-performance liquid chromatography. The two compounds were identified by tandem Q-TOF mass spectroscopy as C15 Iturin A (1) and a novel cyclic peptide with a molecular weight of 852.4 Da (2). Both compounds showed good inhibitory activities against three plant fungal pathogens in cylinder-plate diffusion assay. To our best knowledge, this is the first report on a cyclic antifungal peptide with a molecular weight of 852.4 Da. The strong antifungal activity suggests that the B. amyloliquefaciens L-H15 and its bioactive components might provide an alternative resource for the biocontrol of plant diseases and sustainable agriculture. PMID:26123083

  20. Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism.

    PubMed

    Zhang, Xibo; Fang, Yue; Jaiseng, Wurentuya; Hu, Lingling; Lu, Yabin; Ma, Yan; Furuyashiki, Tomoyuki

    2015-01-01

    Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases. PMID:26628015

  1. Establishment of a Novel Model of Onychomycosis in Rabbits for Evaluation of Antifungal Agents ?

    PubMed Central

    Shimamura, Tsuyoshi; Kubota, Nobuo; Nagasaka, Saori; Suzuki, Taku; Mukai, Hideki; Shibuya, Kazutoshi

    2011-01-01

    We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents. PMID:21555762

  2. In Vitro Susceptibilities of Candida albicans Isolates to Antifungal Agents in Tokat, Turkey

    PubMed Central

    Yenisehirli, Gulgun; Bulut, Nermin; Yenisehirli, Aydan; Bulut, Yunus

    2015-01-01

    Background: Candida albicans is the pathogenic species most commonly isolated from fungal infections. Management of these infections depends on the immune status of the host, severity of disease, and the choice of antifungal drug. In spite of the development of new antifungal drugs, epidemiological studies have shown that resistance to antifungal drugs in C. albicans strains is becoming a serious problem. Objectives: The aim of this study was to evaluate the in vitro susceptibility of C. albicans isolates to ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, caspofungin, and anidulafungin. Materials and Methods: A total of 201 C. albicans isolates were collected from clinical specimens. Antifungal susceptibility tests were performed using the Etest. Results: All the tested C. albicans isolates were found to be susceptible to amphotericin B and anidulafungin. Although none of the isolates showed resistance to caspofungin, 15% of the isolates were classified as showing intermediate resistance. The resistance rates of C. albicans isolates to ketoconazole, fluconazole, itraconazole, voriconazole and posaconazole were 32%, 34%, 21%, 14% and 14%, respectively. Conclusions: Our findings indicate that resistance of C. albicans strains to azoles is more common in Tokat, Turkey. Therefore, a strategy to control the inappropriate and widespread use of antifungal drugs is urgently needed. Fungal culturing and antifungal susceptibility testing will be useful in patient management as well as resistance surveillance. PMID:26495115

  3. Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

    PubMed Central

    Forastiero, A.; Mesa-Arango, A. C.; Alastruey-Izquierdo, A.; Alcazar-Fuoli, L.; Bernal-Martinez, L.; Pelaez, T.; Lopez, J. F.; Grimalt, J. O.; Gomez-Lopez, A.; Cuesta, I.; Zaragoza, O.

    2013-01-01

    Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies. PMID:23877676

  4. Antagonism of antifungal metabolites from Streptomyces griseus H7602 against Phytophthora capsici.

    PubMed

    Nguyen, Xuan Hoa; Naing, Kyaw Wai; Lee, Young Seong; Kim, Yong Hwan; Moon, Jae Hak; Kim, Kil Yong

    2015-01-01

    In this study, evidences for antagonism were established by production of antifungal metabolites from Streptomyces griseus H7602, which were active to inhibit mycelial growth of Phytophthora capsici in the in vitro assays. Mycelial growth and zoosporangia formation of P. capsici was strongly inhibited in the medium containing the cell free culture filtrate of S. griseus H7602. Antifungal metabolites from the cell free culture filtrate of S. griseus H7602 showed substantial antagonistic effects on P. capsici. In addition, a purified antifungal compound was separated from the antifungal metabolites of S. griseus H7602 and identified to be 1H-pyrrole-2-carboxylic acid (PCA) by spectra analyses. PCA showed strong antifungal activity and was evaluated for the first time for its antagonism against P. capsici under in vitro conditions. Minimum inhibitory concentration (MIC) value of PCA was low (4?µg?ml(-1)), and the mycelial growth of P. capsici was almost inhibited at concentration of 64?µg?ml(-1). This study suggests that the PCA may be useful as biofungicides against P. capsici, and the prominent antagonism of antifungal metabolites from S. griseus H7602 highlights it as a candidate for biocontrol of P. capsici. PMID:24554614

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

    PubMed Central

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

    2015-01-01

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

  6. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...0.40 Soybean, seed 0.25 Spearmint, tops 3.0 Star apple 3.0 Strawberry 0.50 Tomato 0.30 Tomato... For Federal Register citations affecting § 180.443, see the List of CFR Sections Affected, which appears in the...

  7. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...following food commodities: Commodity Parts per million Almond 0.1 Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus 0.02 Banana, postharvest...

  8. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...following food commodities: Commodity Parts per million Almond 0.1 Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus 0.02 Banana, postharvest...

  9. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...following food commodities: Commodity Parts per million Almond 0.1 Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus 0.02 Banana, postharvest...

  10. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 10.0 Grape, raisin, waste 25.0 Grape, wet pomace... Tomato, paste 1.0 Vegetable, cucurbit, group 9 0.20 Vegetable, fruiting, group 8, except...Expiration/revocation date Vegetable, foliage of legume,...

  11. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... citations affecting § 180.443, see the List of CFR Sections Affected, which appears in the Finding Aids... Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sapodilla 3.0 Sapote, black 3.0 Sapote, mamey 3.0...

  12. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sapodilla 3.0 Sapote, black 3.0 Sapote, mamey 3.0...

  13. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sapodilla 3.0 Sapote, black 3.0 Sapote, mamey 3.0...

  14. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sapodilla 3.0 Sapote, black 3.0 Sapote, mamey 3.0...

  15. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sapodilla 3.0 Sapote, black 3.0 Sapote, mamey 3.0...

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

    PubMed

    Zeng, Hong; Chen, Xinping; Liang, Jingnan

    2015-01-01

    Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent. PMID:25351709

  17. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels on cell proliferation in the mouse tumorigenesis process are discussed.

  18. An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols.

    PubMed

    Keller, Petra; Müller, Christoph; Engelhardt, Isabel; Hiller, Ekkehard; Lemuth, Karin; Eickhoff, Holger; Wiesmüller, Karl-Heinz; Burger-Kentischer, Anke; Bracher, Franz; Rupp, Steffen

    2015-10-01

    Fungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, including Candida glabrata and Candida krusei (species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3?,6?-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3?,6?-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway. PMID:26248360

  19. Screening of Pharmacologically Active Small Molecule Compounds Identifies Antifungal Agents Against Candida Biofilms

    PubMed Central

    Watamoto, Takao; Egusa, Hiroshi; Sawase, Takashi; Yatani, Hirofumi

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis.

  20. Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A

    PubMed Central

    LI, RUI-FANG; LU, YA-LI; LU, YAN-BO; ZHANG, HUI-RU; HUANG, LIANG; YIN, YANLI; ZHANG, LIN; LIU, SHUAI; LU, ZHIFANG; SUN, YANAN

    2015-01-01

    CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40°C or within a broad pH range (pH 5.0–7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics. PMID:26668630

  1. In vitro antifungal susceptibility testing of Scopulariopsis brevicaulis strains using agar diffusion method.

    PubMed

    Skóra, Magdalena; Macura, Anna B

    2011-01-01

    The genus Scopulariopsis is a common soil saprotroph and has been isolated from air, organic waste and also from plant, animal and human tissues. Scopulariopsis has mainly been associated in humans with superficial mycoses, but it has also been described as the cause of subcutaneous and invasive infections. The most common aetiological agent of infections in humans is Scopulariopsis brevicaulis. This species has been reported to be resistant in vitro to broad-spectrum antifungal agents available today. The aim of the study was to establish in vitro antifungal susceptibility of 35 S. brevicaulis strains against amphotericin B (AMB), flucytosine (FC), caspofungin (CAS), terbinafine (TER), ciclopirox (CIC), voriconazole (VOR), clotrimazole (CTR), miconazole (MCZ), econazole (ECO), ketoconazole (KET), itraconazole (ITR), and fluconazole (FLU). Antifungal susceptibility tests were evaluated by an agar diffusion method (Neo-Sensitabs, Rosco, Denmark). AMB, FC, CAS, ITR and FLU showed no antifungal activity against S. brevicaulis. TER, CIC, CTR, KET, VOR, ECO, and MCZ revealed inhibitory activity for S. brevicaulis, but it varied for each of the drugs. The best antifungal effect was observed for TER and CIC. All isolates had large inhibition zones for TER and CIC. CTR was also inhibitory for all tested S. brevicaulis isolates, but the diameters of inhibition zones were smaller than for TER and CIC. Nearly 89% isolates showed inhibition zones for KET and the mean diameter of the inhibition zone was comparable to CTR. The least antifungal activity exhibited VQR, ECO and MCZ. Because of the multiresistance of S. brevicaulis, infections due to this species may not respond to particular antifungal treatment and other therapeutic approaches should be considered, e.g., combined therapy and/or surgery. PMID:21682097

  2. Nest sanitation through defecation: antifungal properties of wood cockroach feces

    NASA Astrophysics Data System (ADS)

    Rosengaus, Rebeca B.; Mead, Kerry; Du Comb, William S.; Benson, Ryan W.; Godoy, Veronica G.

    2013-11-01

    The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant ?-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations.

  3. Evaluation of the In Vitro Antifungal Activity of Allicin

    PubMed Central

    Yamada, Yasuo; Azuma, Keiz?

    1977-01-01

    Allicin was effective in vitro against Candida, Cryptococcus, Trichophyton, Epidermophyton, and Microsporum. The minimal inhibitory concentrations (MICs) of allicin against these organisms were 3.13 to 6.25 ?g/ml by the agar dilution method and 1.57 to 6.25 ?g/ml by the broth dilution method, using Sabouraud glucose (SG) medium. However decreased activity was demonstrated against Aspergillus. The MIC of allicin against various pathogenic fungi was affected considerably by differences in the experimental conditions, e.g., incubation time, inoculum size, type of medium, and medium pH. The MIC of allicin against Candida, Cryptococcus, and Aspergillus remained constant after more than 3 days of incubation, and that against Dermatophytes remained constant after more than 10 days of incubation. Decreasing the inoculum size increased the susceptibility to allicin. The antifungal activity of allicin was stronger on SG agar medium with a pH of 5.6 than on the same medium with a pH of 6.0 or higher. By microscopical observation, allicin induced morphological abnormalities in hyphae of Trichophyton mentagrophytes Morita. Percent germination of spores of the Morita strain at 24 h in SG agar medium was greatly decreased with an allicin concentration of 3.13 ?g/ml, and the lethal dose for the spores was about four times higher than the fungistatic concentration. These results suggest that allicin inhibits both germination of spores and growth of hyphae. Images PMID:856026

  4. Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.

    PubMed

    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. PMID:26227503

  5. Comparison of In Vitro Antifungal Activities of Efinaconazole and Currently Available Antifungal Agents against a Variety of Pathogenic Fungi Associated with Onychomycosis

    PubMed Central

    Tatsumi, Yoshiyuki; Senda, Hisato; Pillai, Radhakrishnan; Nakamura, Takashi; Sone, Daisuke; Fothergill, Annette

    2013-01-01

    Onychomycosis is a common fungal nail infection in adults that is difficult to treat. The in vitro antifungal activity of efinaconazole, a novel triazole antifungal, was evaluated in recent clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans, common causative onychomycosis pathogens. In a comprehensive survey of 1,493 isolates, efinaconazole MICs against T. rubrum and T. mentagrophytes ranged from ?0.002 to 0.06 ?g/ml, with 90% of isolates inhibited (MIC90) at 0.008 and 0.015 ?g/ml, respectively. Efinaconazole MICs against 105 C. albicans isolates ranged from ?0.0005 to >0.25 ?g/ml, with 50% of isolates inhibited (MIC50) by 0.001 and 0.004 ?g/ml at 24 and 48 h, respectively. Efinaconazole potency against these organisms was similar to or greater than those of antifungal drugs currently used in onychomycosis, including amorolfine, ciclopirox, itraconazole, and terbinafine. In 13 T. rubrum toenail isolates from onychomycosis patients who were treated daily with topical efinaconazole for 48 weeks, there were no apparent increases in susceptibility, suggesting low potential for dermatophytes to develop resistance to efinaconazole. The activity of efinaconazole was further evaluated in another 8 dermatophyte, 15 nondermatophyte, and 10 yeast species (a total of 109 isolates from research repositories). Efinaconazole was active against Trichophyton, Microsporum, Epidermophyton, Acremonium, Fusarium, Paecilomyces, Pseudallescheria, Scopulariopsis, Aspergillus, Cryptococcus, Trichosporon, and Candida and compared favorably to other antifungal drugs. In conclusion, efinaconazole is a potent antifungal with a broad spectrum of activity that may have clinical applications in onychomycosis and other mycoses. PMID:23318803

  6. Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

    PubMed Central

    Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

    2014-01-01

    Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

  7. Allergic Fungal Rhinosinusitis and the Unified Airway: the Role of Antifungal Therapy in AFRS.

    PubMed

    Ryan, Matthew W; Clark, Christopher M

    2015-12-01

    Allergic fungal sinusitis (AFS) or rhinosinusitis (AFRS) is a form of polypoid chronic rhinosinusitis that is believed to be due to hypersensitivity to fungal antigens. The disease is characterized by type 1 hypersensitivity to fungal allergens, dramatically elevated total serum IgE, accumulation of thick eosinophil-laden mucin with non-invasive fungal hyphae within the paranasal sinuses, nasal polyposis, and sinus bony remodeling. Because of many clinicopathologic similarities to allergic bronchopulmonary aspergillosis (ABPA), these conditions can be considered analogous examples of disease in the unified airway. However, these conditions rarely occur together and their treatment differs. The treatment of AFRS relies upon surgical removal of fungal hyphae in eosinophilic mucin, while antifungal therapy is used to clear fungi from the airways in ABPA. Several uncontrolled studies suggest there may be some benefit to antifungal agents in AFRS, but randomized trials of topical and systemic antifungal therapies have not shown beneficial results in chronic rhinosinusitis (CRS). Antifungal treatment within the sinonasal cavities does not appear to be an effective approach for most chronic sinusitis, and antifungal therapy for AFRS is unproven. PMID:26515449

  8. Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents

    PubMed Central

    Komoto, Tatiana Takahasi; Bitencourt, Tamires Aparecida; Silva, Gabriel; Beleboni, Rene Oliveira; Marins, Mozart; Fachin, Ana Lúcia

    2015-01-01

    Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid ?-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8?µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60?µM to ?-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. PMID:26257814

  9. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target

    PubMed Central

    Dobb, Katharine S.; Kaye, Sarah J.; Beckmann, Nicola; Thain, John L.; Stateva, Lubomira; Birch, Mike; Oliver, Jason D.

    2015-01-01

    Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds. PMID:26606674

  10. Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents.

    PubMed

    Komoto, Tatiana Takahasi; Bitencourt, Tamires Aparecida; Silva, Gabriel; Beleboni, Rene Oliveira; Marins, Mozart; Fachin, Ana Lúcia

    2015-01-01

    Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid ?-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8?µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60?µM to ?-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. PMID:26257814

  11. Gastrodianin-like mannose-binding proteins: a novel class of plant proteins with antifungal properties.

    PubMed

    Wang, X; Bauw, G; Van Damme, E J; Peumans, W J; Chen, Z L; Van Montagu, M; Angenon, G; Dillen, W

    2001-03-01

    The orchid Gastrodia elata depends on the fungus Armillaria mellea to complete its life cycle. In the interaction, fungal hyphae penetrate older, nutritive corms but not newly formed corms. From these corms, a protein fraction with in vitro activity against plant-pathogenic fungi has previously been purified. Here, the sequence of gastrodianin, the main constituent of the antifungal fraction, is reported. Four isoforms that encoded two different mature proteins were identified at the cDNA level. Another isoform was detected in sequenced peptides. Because the antifungal activity of gastrodianins produced in and purified from Escherichia coli and Nicotiana tabacum was comparable to that of gastrodianin purified from the orchid, gastrodianins are the active component of the antifungal fractions. Gastrodianin accumulation is probably an important part of the mechanism by which the orchid controls Armillaria penetration. Gastrodianin was found to be homologous to monomeric mannose-binding proteins of other orchids, of which at least one (Epipactis helleborine mannose-binding protein) also displayed in vitro antifungal activity. This establishes the gastrodianin-like proteins (GLIPs) as a novel class of antifungal proteins. PMID:11319032

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

    PubMed

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

    2014-10-01

    Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis. PMID:25005365

  13. In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds.

    PubMed

    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

    2011-10-01

    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. (MIC(90) of ?0.008 to 0.06 ?g/ml), except for Candida krusei (MICs of 2 to >32 ?g/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 (MIC(90) of 0.13 ?g/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 ?g/ml), Scedosporium prolificans (MIC of 0.03 ?g/ml), and Paecilomyces lilacinus (MICs of 0.06 ?g/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

  14. Antifungal Susceptibility Testing with Etest for Candida Species Isolated from Patients with Oral Candidiasis

    PubMed Central

    Song, You Bum; Ha, Gyoung Yim; Kim, Heesoo

    2015-01-01

    Background The necessity of performing antifungal susceptibility tests is recently increasing because of frequent cases of oral candidiasis caused by antifungal-resistant Candida species. The Etest (BioMerieux, Marcy l'Etoile, France) is a rapid and easy-to-perform in vitro antifungal susceptibility test. Objective The purpose of this study was to determine the minimal inhibitory concentrations (MICs) of antifungal agents by using the Etest for Candida species isolated from patients with oral candidiasis. Methods Forty-seven clinical isolates of Candida species (39 isolates of Candida albicans, 5 isolates of C. glabrata, and 3 isolates of C. tropicalis) were tested along with a reference strain (C. albicans ATCC 90028). The MIC end points of the Etest for fluconazole, itraconazole, voriconazole, and amphotericin B susceptibility were read after the 24-hour incubation of each isolate on RPMI 1640 agar. Results All Candida isolates were found susceptible to voriconazole and amphotericin B. However, all five isolates of C. glabrata were resistant to itraconazole, among which two isolates were also resistant to fluconazole. Conclusion This study revealed that the Etest represented a simple and efficacious method for antifungal susceptibility testing of Candida species isolated from oral candidiasis patients. Therefore, voriconazole and amphotericin B should be recommended as effective alternatives for the treatment of oral candidiasis. PMID:26719641

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

    PubMed

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

    2015-09-01

    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

  16. Vulgarone B, the antifungal constituent in the steam-distilled fraction of Artemisia douglasiana.

    PubMed

    Meepagala, Kumudini M; Kuhajek, Jeanne M; Sturtz, George D; Wedge, David E

    2003-08-01

    Antifungal activity of the steam distilled essential oil fraction of Artemisia douglasiana was detected by bioautography on silica gel TLC plates against three Colletotrichum spp. The active principle was isolated by bioassay-directed fractionation using column chromatography followed by crystallization and was characterized as vulgarone B by 1H and 13C NMR and GC-MS. Antifungal activity of vulgarone B was further evaluated using 96-well microtiter assay against Colletotrichum acatatum, C. fragariae, C. gloeosporioides, and Botrytis cinerea. In addition, the antifungal activity of vulgarone B and verbenone, and their corresponding alcohols was tested by bioautography and microtiter assay. Structure-activity studies revealed that the alpha, beta-unsaturated carbonyl functionality is a prerequisite for the antifungal activity of these mono and sesquiterpene ketones. This is the first report of antifungal activity of vulgarone B. The yield of essential oil from A. douglasiana is about 0.6-0.8% by weight of the dry material, including plant stems. PMID:12956506

  17. Isolation and identification of antifungal peptides from Bacillus BH072, a novel bacterium isolated from honey.

    PubMed

    Zhao, Xin; Zhou, Zhi-jiang; Han, Ye; Wang, Zhan-zhong; Fan, Jie; Xiao, Hua-zhi

    2013-11-01

    A bacterial strain BH072 isolated from a honey sample showed antifungal activity against mold. Based on morphological, biochemical, physiological tests, and analysis of 16S rDNA sequence, the strain was identified to be a new subspecies of Bacillus sp. It had a broad spectrum of antifungal activity against various mold, such as Aspergillus niger, Pythium, and Botrytis cinerea. Six pairs of antifungal genes primers were designed and synthesized, and ituA, hag, tasA genes were detected by PCR analysis. The remarkable antifungal activity could be associated with the co-production of these three peptides. One of them was purified by 30-40% ammonium sulfate precipitation, Sephadex G-75 gel filtration and anion exchange chromatography on D201 resin. The purified peptide was estimated to be 35.615 kDa and identified to be flagellin by micrOTOF-Q II. By using methanol extraction, another substance was isolated from fermentation liquor, and determined to be iturin with liquid chromatography-mass spectrometry (LC-MS) method. The third possible peptide encoded by tasA was not isolated in this study. The culture liquor displayed antifungal activity in a wide pH range (5.0-9.0) and at 40-100°C. The result of the present work suggested that Bacillus BH072 might be a bio-control bacterium of research value. PMID:23545354

  18. Antifungal Susceptibilities, Varieties, and Electrophoretic Karyotypes of Clinical Isolates of Cryptococcus neoformans from Brazil, Chile, and Venezuela

    PubMed Central

    Calvo, Belinda M.; Colombo, Arnaldo L.; Fischman, Olga; Santiago, A.; Thompson, L.; Lazera, Marcia; Telles, Flavio; Fukushima, Kazutaka; Nishimura, Kazuko; Tanaka, Reiko; Myiajy, Makoto; Moretti-Branchini, M. Luiza

    2001-01-01

    One hundred clinical isolates of Cryptococcus neoformans from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients from Brazil, Chile, and Venezuela were separated according to varieties and tested for antifungal susceptibility. A high susceptibility to antifungal agents was observed among all the isolates. The electrophoretic karyotyping of 51 strains revealed good discrimination among Cryptococcus neoformans var. neoformans strains. PMID:11376089

  19. Blockade of HERG cardiac K+ current by antifungal drug miconazole

    PubMed Central

    Kikuchi, Kan; Nagatomo, Toshihisa; Abe, Haruhiko; Kawakami, Kazunobu; Duff, Henry J; Makielski, Jonathan C; January, Craig T; Nakashima, Yasuhide

    2004-01-01

    Miconazole, an imidazole antifungal agent, is associated with acquired long QT syndrome and ventricular arrhythmias. Miconazole increases the plasma concentration of QT-prolonging drugs by inhibiting the hepatic cytochrome P450 metabolic pathway, but whether it has direct effects on cardiac ion channels has not been elucidated. To determine the mechanism underlying these clinical findings, we investigated the effect of miconazole on human ether-a-go-go-related gene (HERG) K+ channels. HERG channels were heterologously expressed in human embryonic kidney 293 (HEK293) cells and whole-cell currents were recorded using a patch-clamp technique (23°C). Miconazole inhibited HERG peak tail current in a concentration-dependent manner (0.4–40??M) with an IC50 of 2.1??M (n=3–5 cells at each concentration, Hill coefficient 1.2). HERG block was not frequency-dependent. It required channel activation, occurred rapidly, and had very slow dissociation properties. The activation curve was shifted in a negative direction (V1/2: ?9.5±2.3?mV in controls and ?15.3±2.4?mV after 4??M miconazole, P<0.05, n=6). Miconazole did not change other channel kinetics (activation, deactivation, onset of inactivation, recovery from inactivation, steady-state inactivation). The S6 domain mutation, F656C, abolished the inhibitory action of miconazole on HERG current indicating that miconazole preferentially binds to an aromatic amino-acid residue within the pore-S6 region. Our findings indicate that miconazole causes HERG channel block by binding to a common drug receptor, and this involves preferential binding to activated channels. Thus, miconazole prolongs the QT interval by direct inhibition of HERG channels. PMID:15778703

  20. Biogenic silver nanoparticles: efficient and effective antifungal agents

    NASA Astrophysics Data System (ADS)

    Netala, Vasudeva Reddy; Kotakadi, Venkata Subbaiah; Domdi, Latha; Gaddam, Susmila Aparna; Bobbu, Pushpalatha; Venkata, Sucharitha K.; Ghosh, Sukhendu Bikash; Tartte, Vijaya

    2015-06-01

    Biogenic synthesis of silver nanoparticles (AgNPs) by exploiting various plant materials is an emerging field and considered green nanotechnology as it involves simple, cost effective and ecofriendly procedure. In the present study AgNPs were successfully synthesized using aqueous callus extract of Gymnema sylvestre. The aqueous callus extract treated with 1nM silver nitrate solution resulted in the formation of AgNPs and the surface plasmon resonance (SPR) of the formed AgNPs showed a peak at 437 nm in the UV Visible spectrum. The synthesized AgNPs were characterized using Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), and X-ray diffraction spectroscopy (XRD). FTIR spectra showed the peaks at 3333, 2928, 2361, 1600, 1357 and 1028 cm-1 which revealed the role of different functional groups possibly involved in the synthesis and stabilization of AgNPs. TEM micrograph clearly revealed the size of the AgNPs to be in the range of 3-30 nm with spherical shape and poly-dispersed nature; it is further confirmed by Particle size analysis that the stability of AgNPs is due its high negative Zeta potential (-36.1 mV). XRD pattern revealed the crystal nature of the AgNPs by showing the braggs peaks corresponding to (111), (200), (220) and (311) planes of face-centered cubic crystal phase of silver. Selected area electron diffraction pattern showed diffraction rings and confirmed the crystalline nature of synthesized AgNPs. The synthesized AgNPs exhibited effective antifungal activity against Candida albicans, Candida nonalbicans and Candida tropicalis.

  1. Antifungal drug resistance evoked via RNAi-dependent epimutations.

    PubMed

    Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan; Bastidas, Robert J; Nicolás, Francisco E; Granek, Joshua A; Mieczkowski, Piotr; Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M; Cardenas, Maria E; Heitman, Joseph

    2014-09-25

    Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidylprolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants. FK506-resistant epimutants readily reverted to the drug-sensitive wild-type phenotype when grown without exposure to the drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNAs and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves the generation of a double-stranded RNA trigger intermediate using the fkbA mature mRNA as a template to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes. PMID:25079329

  2. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites.

    PubMed

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong; An, Zhiqiang; Bills, Gerald F

    2015-07-01

    The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandin-exclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineage-specific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities. PMID:26024901

  3. FR207944, an antifungal antibiotic from Chaetomium sp. no. 217 I. Taxonomy, fermentation, and biological properties.

    PubMed

    Kobayashi, Motoo; Kanasaki, Ryuichi; Sato, Ikuko; Abe, Fumie; Nitta, Kumiko; Ezaki, Masami; Sakamoto, Kazutoshi; Hashimoto, Michizane; Fujie, Akihiko; Hino, Motohiro; Hori, Yasuhiro

    2005-03-01

    An antifungal antibiotic, FR207944, was isolated from the culture broth of a fungal strain Chaetomium sp. no. 217. FR207944 is a triterpene glucoside with antifungal activity against Aspergillus fumigatus and Candida albicans. Specifically, FR207944 exhibits in vitro and in vivo antifungal activity against A. fumigatus. The effects of FR207944 on the morphology of A. fumigatus were shown to be similar to those of FR901379, a known 1,3-beta-glucan synthase inhibitor. The MECs of FR207944 against A. fumigatus FP1305 and C. albicans FP633 in micro-broth dilution test were 0.039 and 1.6 mug/ml respectively. FR207944 showed good potency by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED(50)s of 5.7 and 17 mg/kg respectively. PMID:15784979

  4. Facile fabrication of graphene oxide loaded with silver nanoparticles as antifungal materials

    NASA Astrophysics Data System (ADS)

    Cui, Jianghu; Yang, Yunhua; Zheng, Mingtao; Liu, Yingliang; Xiao, Yong; Lei, Bingfu; Chen, Wei

    2014-12-01

    Graphene oxide loaded silver nanoparticles (GO-Ag) were synthesized using a simple method. Our evidence showed that silver nanoparticles (Ag NPs) were successfully loaded on the surface of graphene oxide sheets. The antifungal property of GO-Ag composites was investigated. The results revealed that the obtained GO-Ag composites exhibit enhanced antifungal property in comparison with that of Ag NPs. The toxicity of GO-Ag and Ag NPs were systematically evaluated. The study of cell viability, lactate dehydrogenase, reactive oxygen species, apoptosis/necrosis and hemolysis revealed that GO-Ag composites have lower cytotoxicity and better blood compatibility than Ag NPs. Therefore, these findings provide nanotoxicological information regarding GO-Ag composites which may be alternative antifungal materials in their application of biomedical fields.

  5. Report: Antibacterial and antifungal activities of leaf extract of Achyranthes aspera (Amaranthaceae) from Pakistan.

    PubMed

    Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Shah, Waheed Ali; Shah, Yasar; Ahmad, Lateef; Hassan, Muhammad; Khan, Abuzar; Khan, Abad

    2015-09-01

    Alcoholic extract and various fractions of Achyranthes aspera leaves, traditionally used in Pakistan for treatment of infectious diseases was screened for in vitro antibacterial and antifungal activity. The chloroform and butanol fractions were found to be the most active among the fractions, showing considerable antibacterial activity against Shigella flexneri and Escherichia coli. The highest activity was found in the ethylacetate fraction (17 mm zone of inhibition) against gram-negative (Salmonella typhi) bacteria, with MIC value as 0.29 mg/mL. In antifungal screening, moderate activity was shown by the chloroform fraction (50 % inhibition) against Microsporum canis, with MIC value as 0.25mg/mL. Considerable level of antifungal activity was depicted by crude extract, hexane and butanol fractions against Aspergillus flavus and Microsporum canis. The ability of various extracts of Achyranthes aspera to inhibit different strains of fungi and bacteria indicates its potential use for the treatment of microbial infections. PMID:26408900

  6. Discrimination of Modes of Action of Antifungal Substances by Use of Metabolic Footprinting

    PubMed Central

    Allen, Jess; Davey, Hazel M.; Broadhurst, David; Rowland, Jem J.; Oliver, Stephen G.; Kell, Douglas B.

    2004-01-01

    Diploid cells of Saccharomyces cerevisiae were grown under controlled conditions with a Bioscreen instrument, which permitted the essentially continuous registration of their growth via optical density measurements. Some cultures were exposed to concentrations of a number of antifungal substances with different targets or modes of action (sterol biosynthesis, respiratory chain, amino acid synthesis, and the uncoupler). Culture supernatants were taken and analyzed for their “metabolic footprints” by using direct-injection mass spectrometry. Discriminant function analysis and hierarchical cluster analysis allowed these antifungal compounds to be distinguished and classified according to their modes of action. Genetic programming, a rule-evolving machine learning strategy, allowed respiratory inhibitors to be discriminated from others by using just two masses. Metabolic footprinting thus represents a rapid, convenient, and information-rich method for classifying the modes of action of antifungal substances. PMID:15466562

  7. Chemical composition, phytotoxic and antifungal properties of Ruta chalepensis L. essential oils.

    PubMed

    Bouabidi, Wafa; Hanana, Mohsen; Gargouri, Samia; Amri, Ismail; Fezzani, Tarek; Ksontini, Mustapha; Jamoussi, Bassem; Hamrouni, Lamia

    2015-01-01

    The chemical composition, and phytotoxic and antifungal activities of the essential oils isolated by using hydrodistillation from the aerial parts of Tunisian rue were evaluated. Significant variations were observed among harvest periods. The analysis of the chemical composition by gas chromatography/mass spectrometry showed that 2-undecanone (33.4-49.8%), 2-heptanol acetate (13.5-15.4%) and ?-pinene (9.8-11.9%) were the main components. The antifungal ability of rue essential oils was tested by using disc agar diffusion against ten plant pathogenic fungi. A high antifungal activity was observed for the essential oil isolated at flowering developmental phase. Furthermore, rue essential oils showed high level of herbicidal activity against several weeds. PMID:25553803

  8. Analysis Of Volatile Fingerprints: A Rapid Screening Method For Antifungal Agents For Efficacy Against Dermatophytes

    NASA Astrophysics Data System (ADS)

    Naraghi, Kamran; Sahgal, Natasha; Adriaans, Beverley; Barr, Hugh; Magan, Naresh

    2009-05-01

    The potential of using an electronic nose (E. nose) for rapid screening dermatophytes to antifungal agents was studied. In vitro, the 50 and 90% effective concentration (EC) values of five antifungal agents for T. rubrum and T. mentagrophytes were obtained by mycelial growth assays. Then, the qualitative volatile production patterns of the growth responses of these fungi to these values were incorporated into solid medium were analysed after 96-120 hrs incubation at 25° C using headspace analyses. Overall, results, using PCA and CA demonstrated that it is possible to differentiate between various treatments within 96-120 hrs. This study showed that potential exists for using qualitative volatile patterns as a rapid screening method for antifungal agents for microorganism. This approach could also facilitate the monitoring of antimicrobial drug activities and infection control programmes and perhaps drug resistance build up in microbial species.

  9. Antifungal activity of Leuconostoc citreum and Weissella confusa in rice cakes.

    PubMed

    Baek, Eunjong; Kim, Hyojin; Choi, Hyejung; Yoon, Sun; Kim, Jeongho

    2012-10-01

    The antifungal activity of organic acids greatly improves the shelf life of bread and bakery products. However, little is known about the effect of lactic acid fermentation on fungal contamination in rice cakes. Here, we show that lactic acid fermentation in rice dough can greatly retard the growth of three fungal species when present in rice cakes, namely Cladosporium sp. YS1, Neurospora sp. YS3, and Penicillium crustosum YS2. The antifungal activity of the lactic acid bacteria against these fungi was much better than that of 0.3% calcium propionate. We found that organic acids including lactic and acetic acid, which are byproducts of lactic fermentation or can be artificially added, were the main antifungal substances. We also found that some Leuconostoc citreum and Weissella confusa strains could be good starter species for rice dough fermentation. These results imply that these lactic acid bacteria can be applicable to improve the preservation of rice cakes. PMID:23124754

  10. Antifungal Action of Ginkgo biloba Outer Seedcoat on Rice Sheath blight

    PubMed Central

    Oh, Tae-Seok; Koo, Han-Mo; Yoon, Hei-Ryeo; Jeong, Nam-Su; Kim, Yeong-Jin; Kim, Chang-Ho

    2015-01-01

    From study of antifungal actions on the rice sheath blight by using the extract of Ginkgo biloba outer seedcoats, we found that the extracts of Ginkgo biloba outer seedcoats of all treatment concentrations had inhibited the rice sheath blight. Among them, the most effective concentration was 250 mg/l at which the growth of microbe was 26 mm and even at the packaging test, when sprayed the G. biloba outer seedcoats at the level of 250 mg/l, the damage rate of the rice sheath blight was identified as 13%. As a result investigating the antifungal activity by separating polysaccharides from G. biloba outer seedcoats, it showed that the clear zone of 14 mm or more was formed at the concentration of 250 mg/l or higher. Based on these results, we concluded that the G. biloba outer seedcoat is a natural substance with the antifungal activity on the rice sheath blight. PMID:25774111

  11. Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

    PubMed Central

    Spampinato, Claudia

    2013-01-01

    The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment of Candida infections is also provided. PMID:23878798

  12. Structure-antifungal activity relationships of polyene antibiotics of the amphotericin B group.

    PubMed

    Tevyashova, Anna N; Olsufyeva, Evgenia N; Solovieva, Svetlana E; Printsevskaya, Svetlana S; Reznikova, Marina I; Trenin, Aleksei S; Galatenko, Olga A; Treshalin, Ivan D; Pereverzeva, Eleonora R; Mirchink, Elena P; Isakova, Elena B; Zotchev, Sergey B; Preobrazhenskaya, Maria N

    2013-08-01

    A comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics and in vitro antifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect the in vitro antifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3 or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were tested in vivo to determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely, N-(L-lysyl)-BSG005 (compound 3n) and, especially, L-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable in in vitro and in vivo tests to AMB and that have better toxicological properties. PMID:23716057

  13. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations.

    PubMed

    Nyilasi, Ildikó; Kocsubé, Sándor; Krizsán, Krisztina; Galgóczy, László; Papp, Tamás; Pesti, Miklós; Nagy, Katalin; Vágvölgyi, Csaba

    2014-02-01

    The investigation of the antifungal activities of drugs whose primary activities are not related to their antimicrobial potential is in the current forefront of research. Statin compounds, which are routinely used as cholesterol-lowering drugs, may also exert direct antimicrobial effects. In this study, the in vitro antifungal activities of various statins (lovastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin and pravastatin) were examined against one isolate each of four dermatophyte species (Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Microsporum gypseum). Basically, statins were effective in inhibiting all dermatophyte studied, but were particularly active against M. canis and T. mentagrophytes. Fluvastatin and simvastatin were active against all of the tested fungi causing a complete inhibition of their growth at very low concentrations (6.25-12.5 ?g/ml). Lovastatin and rosuvastatin had inhibitory effects at higher concentrations (25-128 ?g/ml), while atorvastatin and pravastatin proved the less effective. The in vitro interactions between statins and different antifungals (ketoconazole, itraconazole, fluconazole, amphotericin B, nystatin, griseofulvin, terbinafine and primycin) were also investigated using a standard chequerboard broth microdilution method. Synergetic interactions were observed in several cases, most of them were noticed when statins were combined with terbinafine and the different azoles. Some combinations were particularly active (ketoconazole-simvastatin or terbinafine-simvastatin), as they were found to exert synergistic effect against all of the investigated isolates. The other antifungals showed synergistic interactions with statins in only certain cases. These results suggest that statins exert substantial antifungal effects against dermatophyte fungi and they should be promising components in a combination therapy as they can act synergistically with a number of clinically used antifungal agents. PMID:24004389

  14. Enhanced production of antifungal lipopeptides by Bacillus amyloliquefaciens for biocontrol of postharvest disease.

    PubMed

    Pretorius, D; van Rooyen, J; Clarke, K G

    2015-03-25

    Food security to sustain increasing populations is a global concern. A major factor threatening food security is crop spoilage during postharvest storage. Reduction of postharvest spoilage has mainly been addressed by the application of synthetic chemicals. Bacillus lipopeptides, specifically lipopeptide homologues exhibiting antifungal efficacy, offer an alternative environmentally benign protocol for reduction of postharvest phytopathogens. This work is directed towards Bacillus lipopeptide production for biocontrol of postharvest phytopathogens in general and fungal phytopathogens in particular. Bacillus amyloliquefaciens DSM 23117 was identified as an organism with superior potential for lipopeptide production, via screening of 4 Bacillus candidates, in terms of antifungal lipopeptide concentration, yield, productivity and preferred homologue ratio. Efficacy of B. amyloliquefaciens lipopeptides against Botrytis cinerea substantiated appropriateness of this Bacillus species. Subsequent process modification of B. amyloliquefaciens cultures demonstrated that the concentration and ratio of the lipopeptides were significantly influenced by process conditions and further, distinguished nitrate and oxygen availability as key parameters defining optimal lipopeptide production. Discrete B. amyloliquefaciens cultures supplied with 4, 8, 10 and 12 g/L NH4NO3 demonstrated optimal lipopeptide concentration, yield and productivity, with respect to both total and antifungal lipopeptides, in the culture containing 8 g/L NH4NO3. Enhancement of total and antifungal lipopeptide kinetics similar to those quantified on increasing the nitrate from 4 to 8 g/L NH4NO3 were exhibited in B. amyloliquefaciens cultures when the oxygen in the sparge gas was increased from 21 to 30 mol%. The enhancement of lipopeptide production under conditions of increased nitrate and increased oxygen supply is explained in terms of increased availability of nitrogen for synthesis. This work has highlighted key parameters for maximisation of Bacillus lipopeptide production and manipulation of antifungal/surfactin ratios for optimum efficacy and informs on future development of process strategies towards production optimisation of antifungal lipopeptides as a green alternative to synthetic chemicals. PMID:25541516

  15. A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs.

    PubMed

    Kim, Jeongmi; Cho, Yong-Joon; Do, Eunsoo; Choi, Jaehyuk; Hu, Guanggan; Cadieux, Brigitte; Chun, Jongsik; Lee, Younghoon; Kronstad, James W; Jung, Won Hee

    2012-11-01

    The high-affinity reductive iron uptake system that includes a ferroxidase (Cfo1) and an iron permease (Cft1) is critical for the pathogenesis of Cryptococcus neoformans. In addition, a mutant lacking CFO1 or CFT1 not only has reduced iron uptake but also displays a markedly increased susceptibility to azole antifungal drugs. Altered antifungal susceptibility of the mutants was of particular interest because the iron uptake system has been proposed as an alternative target for antifungal treatment. In this study, we used transcriptome analysis to begin exploring the molecular mechanisms of altered antifungal susceptibility in a cfo1 mutant. The wild-type strain and the cfo1 mutant were cultured with or without the azole antifungal drug fluconazole and their transcriptomes were compared following sequencing with Illumina Genome Analyzer IIx (GAIIx) technology. As expected, treatment of both strains with fluconazole caused elevated expression of genes in the ergosterol biosynthetic pathway that includes the target enzyme Erg11. Additionally, genes differentially expressed in the cfo1 mutant were involved in iron uptake and homeostasis, mitochondrial functions and respiration. The cfo1 mutant also displayed phenotypes consistent with these changes including a reduced ratio of NAD(+)/NADH and down-regulation of Fe-S cluster synthesis. Moreover, combination treatment of the wild-type strain with fluconazole and the respiration inhibitor diphenyleneiodonium dramatically increased susceptibility to fluconazole. This result supports the hypothesis that down-regulation of genes required for respiration contributed to the altered fluconazole susceptibility of the cfo1 mutant. Overall, our data suggest that iron uptake and homeostasis play a key role in antifungal susceptibility and could be used as novel targets for combination treatment of cryptococcosis. Indeed, we found that iron chelation in combination with fluconazole treatment synergistically inhibited the growth of C. neoformans. PMID:22975303

  16. Defining targets for investigating the pharmacogenomics of adverse drug reactions to antifungal agents.

    PubMed

    Meletiadis, Joseph; Chanock, Stephen; Walsh, Thomas J

    2008-05-01

    Adverse drug reactions (ADRs) associated with antifungal therapy are major problems in patients with invasive fungal infections. Whether by clinical history or patterns of genetic variation, the identification of patients at risk for ADRs should result in improved outcomes while minimizing deleterious side effects. A major contributing factor to ADRs with antifungal agents relates to drug distribution, metabolism and excretion. Genetic variation in key genes can alter the structure and expression of genes and gene products (e.g., proteins). Thus far, the effort has focused on identifying polymorphisms with either empirical or predicted in silico functional consequences; the best candidate genes encode phase I and II drug-metabolizing enzymes (e.g., CYP2C19 and N-acetyltransferase), plasma proteins (albumin and lipoproteins) and drug transporters (P-glycoprotein and multidrug resistance proteins), which can affect the disposition of antifungal agents, eventually leading to dose-dependent (type A) toxicity. Less is known regarding the key genes that interact with antifungal agents, resulting in idiosyncratic (type B) ADRs. The possible role of certain gene products and genetic polymorphisms in the toxicities of antifungal agents are discussed in this review. The preliminary data address the following: low-density lipoproteins and cholesteryl ester transfer protein in amphotericin B renal toxicity; toll-like receptor 1 and 2 in amphotericin B infusion-related ADRs; phosphodiesterase 6 in voriconazole visual adverse events; flavin-containing monooxygenase, glutathione transferases and multidrug resistance proteins 1 and 2 in ketoconazole and terbinafine hepatotoxicity; CYP enzymes and P-glycoprotein in drug interactions between azoles and coadministered medications; multidrug resistance proteins 8 and 9 on 5-flucytosine bone marrow toxicity; and mast cell activation in caspofungin histamine release. This will focus on high-priority candidate genes, which could provide a starting point for molecular studies to elucidate the potential mechanisms for understanding toxicity associated with antifungal drugs as well as identifying candidate genes for large population prospective genetic association studies. PMID:18466103

  17. Thiourea derivatives incorporating a hippuric acid moiety: synthesis and evaluation of antibacterial and antifungal activities.

    PubMed

    Abbas, Samir Y; El-Sharief, Marwa A M Sh; Basyouni, Wahid M; Fakhr, Issa M I; El-Gammal, Eman W

    2013-06-01

    New series of thiourea derivatives incorporating a hippuric acid moiety have been synthesized through the reaction of 4-hippuric acid isothiocyanate with various nitrogen nucleophiles such as aliphatic amines, aromatic amines, sulfa drugs, aminopyrazoles, phenylhydrazine and hydrazides. The synthesized compounds were tested against bacterial and fungal strains. Most of compounds, such as 2-(4-(3-(3-bromophenyl)thioureido)benzamido)acetic acid and 2-(4-(3-(4-(N-pyrimidin-2-ylsulfamoyl)phenyl)thioureido)benzamido)acetic acid, showed significant antibacterial and antifungal activities. These compounds comprise a new class of promising broad-spectrum antibacterial and antifungal agents. PMID:23644194

  18. Isolation, Purification, and Structural Identification of an Antifungal Compound from a Trichoderma Strain.

    PubMed

    Li, Chong-Wei; Song, Rui-Qing; Yang, Li-Bin; Deng, Xun

    2015-08-01

    Trichoderma strain T-33 has been demonstrated to have inhibitory effect on the fungus species Cytospora chrysosperma. Here, an active antifungal compound was obtained from Trichoderma strain T-33 extract via combined separation technologies, including organic solvent extraction, liquid chromatography, and thin-layer chromatography. The purified compound was further characterized by advanced analytical technologies to elucidate its chemical structure. Results indicated that the active antifungal compound in Trichoderma strain T-33 extract is 2,5- cyclohexadiene-1,4-dione-2,6-bis (1,1-dimethylethyl). PMID:25876599

  19. Development of a rapid, reliable and quantitative method--"SPOTi" for testing antifungal efficacy.

    PubMed

    Rizi, Khalida; Murdan, Sudaxshina; Danquah, Cynthia A; Faull, Jane; Bhakta, Sanjib

    2015-10-01

    A reference method for the antimicrobial susceptibility testing of common fungal pathogens such as dermatophytes, is currently lacking. In this study, we report the successful adaptation of solid agar-based spot culture growth inhibition assay (SPOTi) for dermatophytes, currently being used as a gold-standard in the anti-tubercular drug discovery field. The fungal-SPOTi assay correlated with the disc-diffusion method, and is validated using mycelial plugs. We propose the fungal-SPOTi as a high-throughput alternative to the disc-diffusion and broth micro-dilution anti-fungal assays to screen novel anti-fungals. PMID:26183763

  20. Experimental and theoretical approach of nanocrystalline TiO2 with antifungal activity

    NASA Astrophysics Data System (ADS)

    Longo, Valeria M.; Picon, Francini C.; Zamperini, Camila; Albuquerque, Anderson R.; Sambrano, Julio R.; Vergani, Carlos E.; Machado, Ana L.; Andrés, Juan; Hernandes, Antônio C.; Varela, José A.; Longo, Elson

    2013-07-01

    Using a solvothermal method for this research we synthesized nanocrystalline titanium dioxide (nc-TiO2) anatase particles with a mean diameter of 5.4 nm and evaluated their potential antifungal effect against planktonic cells of Candida albicans without UV radiation. To complement experimental data, we analyzed structural and electronic properties of both the bulk and the (1 0 1) surface of anatase by first-principles calculations. Based on experimental and theoretical results, a reactive O2H and OH species formation mechanism was proposed to explain the key factor which facilitates the antifungal activity.

  1. Antifungal activity in human urine and serum after ingestion of garlic (Allium sativum).

    PubMed Central

    Caporaso, N; Smith, S M; Eng, R H

    1983-01-01

    A fresh extract of garlic (Allium sativum) was administered orally to human volunteers. At intervals, serum and urine were collected and assayed for antifungal activity. The maximum tolerable dose was determined to be 25 ml of garlic extract. Larger amounts caused severe burning sensations in the esophagus and the stomach and vomiting. After oral ingestion of 25 ml of the extract, anticandidal and anticryptococcal activities were detected in undiluted serum 0.5 and 1 h after ingestion. No detectable antifungal activity was found in the excreted urine at any time after oral ingestion. Oral garlic is of limited value in the therapy of human fungal infections. PMID:6870217

  2. The chemical composition of some Lauraceae essential oils and their antifungal activities.

    PubMed

    Simi?, A; Sokovi?, M D; Risti?, M; Gruji?-Jovanovi?, S; Vukojevi?, J; Marin, P D

    2004-09-01

    The antifungal activity of Aniba rosaeodora, Laurus nobilis, Sassafras albidum and Cinnamomum zeylanicum essential oils were investigated against 17 micromycetes. Among the tested fungal species were food poisoning, spoilage fungi, plant and animal pathogens. In order to determine fungistatic and fungicidal concentrations (MIC and MFC) macrodilution and microdilution tests were used. Linalool was the main component in the essential oil of A. rosaeodora, while 1.8-cineole was dominant in L. nobilis. In sassafras essential oil safrole was the major component and in the oil of C. zeylanicum the main component was trans-cinnamaldehyde. The essential oil of cinnamon showed the strongest antifungal activity. PMID:15478207

  3. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group

    PubMed Central

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a–r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  4. Isolation of vulgin, a new antifungal polypeptide with mitogenic activity from the pinto bean.

    PubMed

    Ye, X Y; Ng, T B

    2003-02-01

    An antifungal polypeptide bearing an N-termnial sequence with some homology to chitinases was purified from an extract of pinto beans. The polypeptide, designated vulgin, exerted antifungal activity toward Mycosphaerella arachidicola, Coprinus cornatus, Fusarium oxysporum and Botrytis cinerea. Vulgin inhibited translation in a rabbit reticulocyte lysate system with an IC50 of 4.3 microM and HIV-1 reverse transcriptase activity with an IC50 of 58 microM. Vulgin stimulated in vitro incorporation of methyl [3H] thymidine into mouse splenocytes. PMID:12630696

  5. Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi

    PubMed Central

    de Paula e Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Gullo, Fernanda Patrícia; Sangalli-Leite, Fernanda; de Oliveira, Haroldo Cesar; da Silva, Julhiany de Fátima; Rossi, Suélen Andrea; Benaducci, Tatiane; Wolf, Vanessa Gonçalves; Regasini, Luis Octávio; Petrônio, Maicon Segalla; Silva, Dulce Helena Siqueira; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José Soares

    2014-01-01

    This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action. PMID:25505923

  6. Antifungal suscepitibility profile of candida spp. oral isolates obtained from denture wearers

    PubMed Central

    Lyon, J.P.; Moreira, L.M.; Cardoso, M.A.G.; Saade, J.; Resende, M.A.

    2008-01-01

    Denture stomatitis is an inflammatory condition that occurs in denture wearers and is frequently associated with Candida yeasts. Antifungal susceptibility profiles have been extensively evaluated for candidiasis patients or immunosupressed individuals, but not for healthy Candida carriers. In the present study, fluconazole, itraconazole, voriconazole, terbinafine and 5-flucytosin were tested against 109 oral Candida spp. isolates. All antifungal agents were effective against the samples tested except for terbinafine. This work might provide epidemiological information about Candida spp. drug susceptibility in oral healthy individuals. PMID:24031286

  7. Dolichin, a new chitinase-like antifungal protein isolated from field beans (Dolichos lablab).

    PubMed

    Ye, X Y; Wang, H X; Ng, T B

    2000-03-01

    An antifungal protein, possessing a molecular weight of 28 kDa and an N-terminal sequence resembling chitinases, has been purified from the seeds of the field bean Dolichos lablab. The procedure involved extraction with aqueous buffer, affinity chromatography on Affi-gel blue gel, and ion exchange chromatography on CM-Sepharose. The protein, designated dolichin, exhibited antifungal activity against the fungi Fusarium oxysporum, Rhizoctonia solani, and Coprinus comatus. Dolichin was capable of inhibiting human immunodeficiency virus (HIV) reverse transcriptase and alpha- and beta-glucosidases which are glycohydrolases implicated in HIV infection. It had very low ribonuclease and cell-free translation-inhibitory activities. PMID:10694493

  8. Mitochondria and Fungal Pathogenesis: Drug Tolerance, Virulence, and Potential for Antifungal Therapy?

    PubMed Central

    Shingu-Vazquez, Miguel; Traven, Ana

    2011-01-01

    Recently, mitochondria have been identified as important contributors to the virulence and drug tolerance of human fungal pathogens. In different scenarios, either hypo- or hypervirulence can result from changes in mitochondrial function. Similarly, specific mitochondrial mutations lead to either sensitivity or resistance to antifungal drugs. Here, we provide a synthesis of this emerging field, proposing that mitochondrial function in membrane lipid homeostasis is the common denominator underlying the observed effects of mitochondria in drug tolerance (both sensitivity and resistance). We discuss how the contrasting effects of mitochondrial dysfunction on fungal drug tolerance and virulence could be explained and the potential for targeting mitochondrial factors for future antifungal drug development. PMID:21926328

  9. The expenditures related to the use of antifungal drugs in patients with hematological cancers: a cost analysis

    PubMed Central

    Gedik, Habip

    2015-01-01

    Objective The aim of this study is to analyze the expenditures related to the use of antifungal drugs in patients with hematological malignancies. Methods In this retrospective study, the expenditures related to use of antifungal drugs for treatment of invasive fungal infections in patients with hematological malignancies between November 2010 and November 2012 were analyzed. Expenditures of antifungal drugs were calculated by converting the price billed to the Republic of Turkey Social Security Institution per patient using the US dollar ($) exchange rate. Results We retrospectively analyzed the expenditures related to the use of antifungal drugs in 282 febrile episodes of 126 neutropenic patients. Voriconazole (VOR), caspofungin, and liposomal amphotericin B (L-AmB) were administered as a first-line antifungal therapy to treat 72 febrile episodes of 65 neutropenic patients, 45 febrile episodes of 37 neutropenic patients, and 34 febrile episodes of 32 neutropenic patients, respectively. The expenditures related to the use of antifungal drugs per febrile neutropenic episode were $3,857.85 for VOR; $15,783.34 for caspofungin, and $21,561.02 for L-AmB, respectively. The expenditure related to the use of posaconazole (POS) was $32,167.39 per patient for primary or secondary prophylaxis. Conclusion Improving conditions in the patient’s room, choosing pre-emptive antifungal treatment instead of empirical antifungal treatment, switching to tablet form of VOR after initiation of its intravenous form, secondary prophylaxis with VOR against invasive aspergillosis, primary prophylaxis with POS in high-risk patients, and choosing less L-AmB as being an alternative to other antifungal drugs, may reduce expenditures related to the use of antifungal drugs in the treatment of invasive fungal infections during febrile neutropenic episodes of patients with hematological malignancies. PMID:26622185

  10. 76 FR 27261 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ...acute dietary exposure, EPA used food consumption information from the U.S. Department...exposure assessment EPA used the food consumption data from the USDA 1994-1996...CSFII. As to residue levels in food, EPA used tolerance levels...

  11. 76 FR 27261 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... Federal Register of March 19, 2010 (75 FR 13277) (FRL-8813- 2), EPA issued a notice pursuant to section... numerous previous occasions. Refer to Federal Register 70 FR 37686, June 30, 2005; 70 FR 1354, January 7, 2005; 69 FR 63096, October 29, 2004 for the Agency's response to these objections. V....

  12. 77 FR 38199 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ...10-10 at 8.0 ppm; fruit, stone, group 12, except plum at...that the existing tolerance for stone fruit group 12 at 1.0 ppm...malformations of the lung and kidneys) were reported at doses that...Tomato, Citrus Fruit, and Stone fruit.'' B....

  13. 77 FR 38199 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ....gov/dockets . II. Summary of Petitioned-For Tolerances In the Federal Register of July 20, 2011 (76 FR... Register of Wednesday, May 11, 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure... Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993)....

  14. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ...mg/kg/day and above. In rabbits, developmental toxicity occurred...rudimentary ribs occurred in rat and rabbit fetuses. Increased cleft...USDA) National Health and Nutrition Examination Survey, What...developmental toxicity study in rabbits, neither quantitative...

  15. 77 FR 75039 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    .... Summary of Petitioned-for Tolerance In the Federal Register of November 9, 2011 (Volume 76, FR 69690) (FRL..., 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure from food and feed uses. In..., entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993). Because this final rule...

  16. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... . II. Summary of Petitioned-For Tolerance In the Federal Register of May 23, 2012 (Volume 77, FR 30481... Register of Wednesday, May 11, 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure... actions from review under Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR...

  17. Antifungal activity of 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone against Candida albicans: evidence for the antifungal mode of action.

    PubMed

    Soberón, José R; Lizarraga, Emilio F; Sgariglia, Melina A; Juárez, María B Carrasco; Sampietro, Diego A; Altabef, Aida Ben; Catalán, César A N; Vattuone, Marta A

    2015-11-01

    The main secondary metabolite of Senecio nutans is 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (4HMBA). The antifungal activity of this compound and three derivatives was assessed using Candida albicans. 4HMBA exhibited the highest antifungal activity among the assayed compounds. The Fractional Inhibitory Concentration (FIC = 0.133) indicated a synergistic fungicidal effect of 4HMBA (5 mg L(-1)) and fluconazole (FLU) (0.5 mg L(-1)) against the C. albicans reference strain (ATCC 10231). Microscopy showed that 4HMBA inhibits filamentation and reduces cell wall thickness. Our findings suggest that 4HMBA is an interesting compound to diminish resistance to commercial fungistatic drugs such as fluconazole. PMID:26342699

  18. [A contribution to the stereospecific synthesis of antifungal imidazolyloxime-ethers/Oxiconazole nitrate (Sgd 301-76), a new broadspectrum antifungal agent (author's transl)].

    PubMed

    Mixich, G; Thiele, K

    1979-01-01

    A stereospecific synthesis of antifungal imidazolyloxime-ether derivatives is reported. The compound Sgd 301-76 (oxiconazole nitrate) = (Z)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-O-(2,4-dichlorobenzyl)-ethanoneoxime-nitrate was selected for clinical trials. The (E)- and (Z)-assignments, respectively, were made on the basis of 1-H-NMR-spectral data. PMID:583212

  19. Beta-lactam antifungals. II. Enantiocontrolled synthesis of (2R,5S)-2-hydroxymethyl-1-carbapenam, the carba-analog of a clavam antifungal.

    PubMed

    Konosu, T; Furukawa, Y; Hata, T; Oida, S

    1991-11-01

    (2R,5S)-2-Hydroxymethyl-1-carbapenam (3), the carba-analog of an antifungal beta-lactam (2R,5S)-2-(hydroxymethyl)calvam (1), was synthesized in an enantiocontrolled manner, starting from the coupling reaction of an optically active phthalimido-acetate (3S,4S)-4 and an allylsilane 7, followed by removal of the phthalimido group that was crucial for asymmetric induction. Hydroboration, protecting-group interconversion, and cyclization gave 3 stereoselectively. PMID:1799936

  20. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.

    PubMed

    Bachhav, Y G; Mondon, K; Kalia, Y N; Gurny, R; Möller, M

    2011-07-30

    Efficient topical drug administration for the treatment of superficial fungal infections would deliver the therapeutic agent to the target compartment and reduce the risk of systemic side effects. However, the physicochemical properties of the commonly used azole antifungals make their formulation a considerable challenge. The objective of the present investigation was to develop aqueous micelle solutions of clotrimazole (CLZ), econazole nitrate (ECZ) and fluconazole (FLZ) using novel amphiphilic methoxy-poly(ethylene glycol)-hexyl substituted polylactide (MPEG-hexPLA) block copolymers. The CLZ, ECZ and FLZ formulations were characterized with respect to drug loading and micelle size. The optimal drug formulation was selected for skin transport studies that were performed using full thickness porcine and human skin. Penetration pathways and micellar distribution in the skin were visualized using fluorescein loaded micelles and confocal laser scanning microscopy. The hydrodynamic diameters of the azole loaded micelles were between 70 and 165nm and the corresponding number weighted diameters (d(n)) were 30 to 40nm. Somewhat surprisingly, the lowest loading efficiency (<20%) was observed for CLZ (the most hydrophobic of the three azoles tested); in contrast, under the same conditions, ECZ was incorporated with an efficiency of 98.3% in MPEG-dihexPLA micelles. Based on the characterization data and preliminary transport experiments, ECZ loaded MPEG-dihexPLA micelles (concentration 1.3mg/mL; d(n)<40nm) were selected for further study. ECZ delivery was compared to that from Pevaryl® cream (1% w/w ECZ), a marketed liposomal formulation for topical application. ECZ deposition in porcine skin following 6h application using the MPEG-dihexPLA micelles was >13-fold higher than that from Pevaryl® cream (22.8±3.8 and 1.7±0.6?g/cm(2), respectively). A significant enhancement was also observed with human skin; the amounts of ECZ deposited were 11.3±1.6 and 1.5±0.4?g/cm(2), respectively (i.e., a 7.5-fold improvement in delivery). Confocal laser scanning microscopy images supported the hypothesis that the higher delivery observed in porcine skin was due to a larger contribution of the follicular penetration pathway. In conclusion, the significant increase in ECZ skin deposition achieved using the MPEG-dihexPLA micelles demonstrates their ability to improve cutaneous drug bioavailability; this may translate into improved clinical efficacy in vivo. Moreover, these micelle systems may also enable targeting of the hair follicle and this will be investigated in future studies. PMID:21397643

  1. Aspergillus tanneri sp. nov, a new pathogenic Aspergillus that causes invasive disease refractory to antifungal therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is the first report documenting fatal invasive aspergillosis caused by a new pathogenic Aspergillus species that is inherently resistant to antifungal drugs. Phenotypic characteristics of A. tanneri combined with the molecular approach enabled diagnosis of this new pathogen. This study undersco...

  2. In vitro antifungal oral drug and drug-combination activity against onychomycosis causative dermatophytes.

    PubMed

    Santos, D A; Hamdan, J S

    2006-06-01

    We present the results of studies of the in vitro susceptibility of 52 isolates of Trichophyton rubrum and 40 of Trichophyton mentagrophytes to griseofulvin, terbinafine, itraconazole, ketoconazole, fluconazole and cyclopiroxolamine. All test strains were recovered from patients with toe nail onychomycosis and the minimum inhibitory concentration (MIC) of each antifungal against both species was individually assessed. In addition, we investigated the MIC of the combination of cyclopiroxolamine and itraconazole and cyclopiroxolamine and ketoconazole. The NCCLS approved procedure M38-A as modified by Santos and Hamdan was employed. The studies of the two drug combinations were conducted with a checkerboard design. Analysis of the data revealed that terbinafine was the most effective in vitro against all isolates, followed in order by itraconazole, cyclopiroxolamine, ketoconazole and fluconazole. We observed no significant difference in the in vitro susceptibility profiles between either species to any of the antifungals (P<0.05). Our in vitro results confirm that terbinafine is the most effective of the antifungals included in this study. Furthermore, synergistic interactions were found in the two drug combinations with all of the dermatophyte test isolates. The latter results are in agreement with clinical data that show synergism between oral and topical antifungals in the treatment of onychomycosis. PMID:16772230

  3. Non-random species loss in bacterial communities reduces antifungal volatile production.

    PubMed

    Hol, W H Gera; Garbeva, Paolina; Hordijk, Cornelis; Hundscheid, P J; Gunnewiek, Paulien J A Klein; Van Agtmaal, Maaike; Kuramae, Eiko E; De Boer, Wietse

    2015-08-01

    The contribution of low-abundance microbial species to soil ecosystems is easily overlooked because there is considerable overlap between metabolic abilities (functional redundancy) of dominant and subordinate microbial species. Here we studied how loss of less abundant soil bacteria affected the production of antifungal volatiles, an important factor in the natural control of soil-borne pathogenic fungi. We provide novel empirical evidence that the loss of soil bacterial species leads to a decline in the production of volatiles that suppress root pathogens. By using dilution-to-extinction for seven different soils we created bacterial communities with a decreasing number of species and grew them under carbon-limited conditions. Communities with high bacterial species richness produced volatiles that strongly reduced the hyphal growth of the pathogen Fusarium oxysporum. For most soil origins loss of bacterial species resulted in loss of antifungal volatile production. Analysis of the volatiles revealed that several known antifungal compounds were only produced in the more diverse bacterial communities. Our results suggest that less abundant bacterial species play an important role in antifungal volatile production by soil bacterial communities and, consequently, in the natural suppression of soil-borne pathogens. PMID:26405729

  4. Antifungal Activity of Chitosan Nanoparticles and Correlation with Their Physical Properties

    PubMed Central

    Ing, Ling Yien; Zin, Noraziah Mohamad; Sarwar, Atif; Katas, Haliza

    2012-01-01

    The need of natural antimicrobials is paramount to avoid harmful synthetic chemicals. The study aimed to determine the antifungal activity of natural compound chitosan and its nanoparticles forms against Candida albicans, Fusarium solani and Aspergillus niger. Chitosan nanoparticles were prepared from low (LMW), high molecular weight (HMW) chitosan and its derivative, trimethyl chitosan (TMC). Particle size was increased when chitosan/TMC concentration was increased from 1 to 3 mg/mL. Their zeta potential ranged from +22 to +55?mV. Chitosan nanoparticles prepared from different concentrations of LMW and HMW were also found to serve a better inhibitory activity against C. albicans (MICLMW = 0.25–0.86?mg/mL and MICHMW = 0.6–1.0?mg/mL) and F. solani (MICLMW = 0.86–1.2?mg/mL and MICHMW = 0.5–1.2?mg/mL) compared to the solution form (MIC = 3?mg/mL for both MWs and species). This inhibitory effect was also influenced by particle size and zeta potential of chitosan nanoparticles. Besides, Aspergillus niger was found to be resistant to chitosan nanoparticles except for nanoparticles prepared from higher concentrations of HMW. Antifungal activity of nanoparticles prepared from TMC was negligible. The parent compound therefore could be formulated and applied as a natural antifungal agent into nanoparticles form to enhance its antifungal activity. PMID:22829829

  5. Improved antifungal activity of amphotericin B-loaded TPGS-b-(PCL-ran-PGA) nanoparticles

    PubMed Central

    Tang, Xiaolong; Jiao, Ronghong; Xie, Chunmei; Xu, Lifa; Huo, Zhen; Dai, Jingjing; Qian, Yunyun; Xu, Weiwen; Hou, Wei; Wang, Jiang; Liang, Yong

    2015-01-01

    To develop amphotericin B-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles (PLGA-TPGS-AMB NPs) for fungal infection treatment, PLGA-TPGS NPs and PLGA NPs were synthesized by a modified double emulsion method and characterized in terms of size and size distribution, morphology and zeta potential. Drug encapsulation efficiency, in vitro drug release, and in vitro/vivo tests against Candida glabrata were completed. The data showed that both of the two AMB-loaded NPs (PLGA-AMB NPs, PLGA-TPGS-AMB NPs) achieved significantly higher level of antifungal effects than water suspended AMB. In comparison with PLGA-AMB NPs, PLGA-TPGS-AMB NPs had a stronger protective effect against candidiasis and gained an advantage of prolonged antifungal efficacy. In conclusion, PLGA-TPGS-AMB NPs system significantly improves AMB bioavailability by increasing the aqueous dispersibility and improving the antifungal activity. And this would be an excellent choice for the antifungal treatment of the entrapped drug because of its low toxicity and higher effectiveness. PMID:26131089

  6. In Vitro Triple Combination of Antifungal Drugs against Clinical Scopulariopsis and Microascus Species.

    PubMed

    Yao, Limin; Wan, Zhe; Li, Ruoyu; Yu, Jin

    2015-08-01

    Broth microdilution checkerboard techniques based on the methodology of the Clinical and Laboratory Standards Institute (CLSI) were employed to study the triple antifungal combination of caspofungin, posaconazole, and terbinafine against 27 clinical isolates of Scopulariopsis and Microascus species. Synergy was observed for 26 isolates, whereas antagonism was observed for Scopulariopsis candida in this study. PMID:26014943

  7. [In vitro antifungal susceptibility profile of Scopulariopsis brevicaulis isolated from onychomycosis].

    PubMed

    Carrillo-Muńoz, Alfonso Javier; Tur-Tur, Cristina; Cárdenes, Délia; Rojas, Florencia; Giusiano, Gustavo

    2015-08-01

    We studied the in vitro antifungal activity profile of amorolfine (AMR), bifonazole (BFZ), clotrimazole (CLZ), econazole (ECZ), fluconazole (FNZ), itraconazole (ITZ), ketoconazole (KTZ), miconazole (MNZ), oxiconazole (OXZ), tioconazole (TCZ) and terbinafine (TRB) against 26 clinical isolates of Scopulariopsis brevicaulis from patients with onychomycosis by means of an standardized microdilution method. Although this opportunistic filamentous fungi was reported as resistant to several broad-spectrum antifungals agents, obtained data shows a better fungistatic in vitro activity of AMR, OXZ and TRB (0.08, 0.3, and 0.35 mg/L, respectively) in comparison to that of CLZ (0.47 mg/L), ECZ (1.48 mg/L), MNZ (1.56 mg/L, BFZ (2.8 mg/L), TCZ (3.33 mg/L), KTZ (3.73 mg/L). FNZ (178.47 mg/L) and ITZ (4.7 mg/L) showed a reduced in vitro antifungal activity against S. brevicaulis. Obtained MICs show the low in vitro antifungal susceptibility of S. brevicaulis to topical drugs for onychomycosis management, with exceptions (AMR, OZX and TRB). PMID:26200030

  8. Dermoscopic Visualization of Vellus Hair Involvement in Tinea Corporis: A Criterion for Systemic Antifungal Therapy?

    PubMed

    Knöpfel, Nicole; del Pozo, Luis Javier; Escudero, Maria del Mar; Martín-Santiago, Ana

    2015-01-01

    Dermoscopy has been shown to be a valuable tool in the diagnosis and monitoring of several infectious diseases. We report a case of tinea corporis in an infant in whom dermoscopy helped us to determine vellus hair involvement, causing treatment to be switched from topical to systemic antifungal therapy. PMID:26205739

  9. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent. PMID:26317080

  10. Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria.

    PubMed

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

    2015-11-01

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

  11. Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum.

    PubMed

    de Oliveira Pereira, Fillipe; Mendes, Juliana Moura; de Oliveira Lima, Edeltrudes

    2013-07-01

    Trichophyton rubrum is a worldwide agent responsible for chronic cases of dermatophytosis which have high rates of resistance to antifungal drugs. Attention has been drawn to the antimicrobial activity of aromatic compounds because of their promising biological properties. Therefore, we investigated the antifungal activity of eugenol against 14 strains of T. rubrum which involved determining its minimum inhibitory concentration (MIC) and effects on mycelial growth (dry weight), conidial germination and morphogenesis. The effects of eugenol on the cell wall (sorbitol protect effect) and the cell membrane (release of intracellular material, complex with ergosterol, ergosterol synthesis) were investigated. Eugenol inhibited the growth of 50% of T. rubrum strains employed in this study at an MIC = 256 ?g/ml, as well as mycelial growth and conidia germination. It also caused abnormalities in the morphology of the dermatophyte in that we found wide, short, twisted hyphae and decreased conidiogenesis. The results of these studies on the mechanisms of action suggested that eugenol exerts antifungal effects on the cell wall and cell membrane of T. rubrum. Eugenol act on cell membrane by a mechanism that seems to involve the inhibition of ergosterol biosynthesis. The lower ergosterol content interferes with the integrity and functionality of the cell membrane. Finally, our studies support the potential use of the eugenol as an antifungal agent against T. rubrum. PMID:23181601

  12. An antifungal mechanism of curcumin lies in membrane-targeted action within Candida albicans.

    PubMed

    Lee, Wonyoung; Lee, Dong Gun

    2014-11-01

    The aim of this study is to investigate the antifungal mechanism of curcumin. This polyphenolic compound has been used traditionally in Asia for medicinal, culinary, and other purposes. Although antifungal effect of curcumin has been reported, this is the first study for its mode of action underlying disruption of plasma membrane in Candida albicans. The leakage of potassium ion from the fungal cytosol and dissipation in membrane potential was detected by bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4 ] staining. We also investigated an increase in membrane permeability in curcumin-treated C. albicans with influx of propidium iodide assay. Fluorescence analysis with 1,6-diphenyl-1,3,5-hexatriene supported the membrane-targeted mechanism of action indicating membrane disruption. On the basis of these results, we studied the effects of curcumin treatment on model membrane to elucidate its antifungal mechanism. Using calcein leakage assays from curcumin-treated large unilamellar vesicles and giant unilamellar vesicles, we found that curcumin has membrane-active mechanism inducing leakage of intracellular component through the flappy membrane. Therefore, this study suggests that curcumin exerts antifungal activity via inducing disruption of fungal plasma membrane. PMID:25380239

  13. Antibacterial and antifungal activities of the endemic species Glaucium vitellinum Boiss. and Buhse

    PubMed Central

    Mehrara, Mina; Halakoo, Mehri; Hakemi-Vala, Mojdeh; Hashemi, Seyyde Jamal; Asgarpanah, Jinous

    2015-01-01

    Objectives: Belonging to Papaveraceae family, Glaucium vitellinum is one of the Persian endemic plants which has not been investigated biologically. The present paper focused on the assessment of the antibacterial and antifungal activities of the total methanol extract and alkaloid sub-fraction of the flowering aerial parts of G. vitellinum. Materials and Methods: The antibacterial and antifungal activities were investigated using cup plate method and disc diffusion assay, respectively. The MIC values of the active samples were determined using micro plate dilution method. Results: The crude extract and alkaloid sub-fraction of G. vitellinum had significant inhibition activity on the growth of S. aureus and S. typhi. From antifungal assay, it is concluded that only the yeast C. albicans, showed a high sensitivity to the extract and especially to the related alkaloid sub-fraction. Conclusions: Regarding the results, G. vitellinum could be employed as a natural antibacterial and antifungal agent against S. aureus, S. typhi, and C. albicans, respectively. Moreover, based on the results of this study, further in vivo and ex vivo confirmatory tests for total methanol extract and alkaloid sub-fraction are recommended. PMID:25767757

  14. Antifungal traits of a 14 kDa maize kernel trypsin inhibitor protein in transgenic cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transgenic cotton plants expressing the maize kernel trypsin inhibitor (TI) protein were produced and evaluated for antifungal traits. This 14 kD trypsin inhibitor protein has been previously associated with resistance to aflatoxin-producing fungus Aspergillus flavus. Successful transformation of ...

  15. Antifungal Activity of Bacillus amyloliquefaciens NJN-6 Volatile Compounds against Fusarium oxysporum f. sp. cubense

    PubMed Central

    Yuan, Jun; Raza, Waseem

    2012-01-01

    Bacillus amyloliquefaciens NJN-6 produces volatile compounds (VOCs) that inhibit the growth and spore germination of Fusarium oxysporum f. sp. cubense. Among the total of 36 volatile compounds detected, 11 compounds completely inhibited fungal growth. The antifungal activity of these compounds suggested that VOCs can play important roles over short and long distances in the suppression of Fusarium oxysporum. PMID:22685147

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

    PubMed

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

    2014-12-01

    In order to search for antifungal from biological origin, we performed a screening of marine microorganisms isolated from seawater, seaweed, sediment and marine invertebrates collected from different coastal areas of the Moroccan Atlantic Ocean. The antifungal activities of these isolates were investigated against the pathogenic yeasts involved in medical mycology. Whole cultures of 34 marine microorganisms were screened for antifungal activities using the method of agar diffusion against four yeasts. The results showed that among the 34 isolates studied, 13 (38%) strains have antifungal activity against at least one out of four yeast species, 11 isolates have anti-Candida albicans CIP 48.72 activity, 12 isolates have anti-C. albicans CIP 884.65 activity, 13 isolates have anti-Cryptococcus neoformans activity and only 6 isolates are actives against Candida tropicalis R2 resistant to nystatin and amphotericin B. Nine isolates showed strong fungicidal activity. Fourteen microorganisms were identified and assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea, and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms could produce more antimicrobials; therefore these marine microorganisms were expected to be potential resources of natural products such as those we research: anti-Candida and anti-Cryptococcus fungicides. PMID:25442916

  17. “In vitro” antifungal activity of ozonized sunflower oil on yeasts from onychomycosis

    PubMed Central

    Guerrer, L.V.; Cunha, K. C.; Nogueira, M. C. L.; Cardoso, C. C.; Soares, M. M. C. N.; Almeida, M. T. G.

    2012-01-01

    The “in vitro” antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii. PMID:24031958

  18. Modeling Production of Antifungal Compounds and their Role in Biocontrol Inhibitory Activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Partial Least Squares (PLS) regression modeling was used to relate the antifungal activity of B. subtilis solid-state fermentation extracts to the individual HPLC peaks from those extracts. A model was developed that predicted bioassay inhibition based on extract HPLC profile (R2 = 0.99). Concentr...

  19. Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones.

    PubMed

    Neumann, Donna M; Cammarata, Amy; Backes, Gregory; Palmer, Glen E; Jursic, Branko S

    2014-01-15

    Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections-a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10?M with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals. PMID:24361188

  20. The Petasis Reaction: Microscale Synthesis of a Tertiary Amine Antifungal Analog

    ERIC Educational Resources Information Center

    Koroluk, Katherine J.; Jackson, Derek A.; Dicks, Andrew P.

    2012-01-01

    Students prepare a tertiary amine antifungal analog in an upper-level undergraduate organic laboratory. A microscale Petasis reaction is performed to generate a liquid compound readily characterized via IR and proton NMR spectroscopy. The biological relevance of the product is highlighted, with the tertiary amine scaffold being an important…

  1. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives.

    PubMed

    Gupta, Deepa; Jain, D K

    2015-01-01

    A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent. PMID:26317080

  2. Chemical Composition and Antifungal Activity of Angelica sinensis Essential Oil Against Three Colletotrichum Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chemical fungicides are an important component in disease management for most crops. As part of a program to discover natural product-based fungicides, several sensitive assay systems have been developed for the evaluation of naturally occurring antifungal agents. In this study, we focused on the di...

  3. Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids

    E-print Network

    Barron, Annelise E.

    Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids that circumvent fungal drug- resistance mechanisms. In this work we used soft X-ray tomogra- phy to image of an entire, fully functional biological system, i.e., in the milieu of a cell (8, 10). Recently, soft X-ray

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

    PubMed

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

    2012-01-01

    We describe methods used to isolate and identify antifungal compounds from actinomycete strains associated with the leaf-cutter ant Acromyrmex octospinosus. These ants use antibiotics produced by symbiotic actinomycete bacteria to protect themselves and their fungal cultivar against bacterial and fungal infections. The fungal cultivar serves as the sole food source for the ant colony, which can number up to tens of thousands of individuals. We describe how we isolate bacteria from leaf-cutter ants collected in Trinidad and analyze the antifungal compounds made by two of these strains (Pseudonocardia and Streptomyces spp.), using a combination of genome analysis, mutagenesis, and chemical isolation. These methods should be generalizable to a wide variety of insect-symbiont situations. Although more time consuming than traditional activity-guided fractionation methods, this approach provides a powerful technique for unlocking the complete biosynthetic potential of individual strains and for avoiding the problems of rediscovery of known compounds. We describe the discovery of a novel nystatin compound, named nystatin P1, and identification of the biosynthetic pathway for antimycins, compounds that were first described more than 60 years ago. We also report that disruption of two known antifungal pathways in a single Streptomyces strain has revealed a third, and likely novel, antifungal plus four more pathways with unknown products. This validates our approach, which clearly has the potential to identify numerous new compounds, even from well-characterized actinomycete strains. PMID:23084933

  5. In Vitro Activities of Eight Antifungal Drugs against 104 Environmental and Clinical Isolates of Aureobasidium pullulans

    PubMed Central

    Najafzadeh, M. Javad; Sutton, Deanna A.; Keisari, M. Saradeghi; Zarrinfar, H.; de Hoog, G. Sybren; Chowdhary, Anuradha

    2014-01-01

    Aureobasidium pullulans is an unusual agent of phaeohyphomycosis. The in vitro activities of antifungals against 104 isolates of Aureobasidium pullulans var. pullulans and A. pullulans var. melanigenum revealed low MIC90s of amphotericin B, posaconazole, and itraconazole. However, they were resistant to fluconazole (?64 ?g/ml) and had high MICs of voriconazole, isavuconazole, caspofungin, and micafungin. PMID:25001309

  6. Plant latex: a promising antifungal agent for post harvest disease control.

    PubMed

    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. PMID:24506041

  7. Susceptibility variation of Malassezia pachydermatis to antifungal agents according to isolate source

    PubMed Central

    Weiler, Caroline Borges; de Jesus, Francielli Pantella Kunz; Nardi, Graziela Habib; Loreto, Érico Silva; Santurio, Janio Morais; Coutinho, Selene Dall’Acqua; Alves, Sydney Hartz

    2013-01-01

    Malassezia pachydermatis is associated with dermatomycoses and otomycosis in dogs and cats. This study compared the susceptibility of M. pachydermatis isolates from sick (G1) and healthy (G2) animals to azole and polyene antifungals using the M27-A3 protocol. Isolates from G1 animals were less sensitive to amphotericin B, nystatin, fluconazole, clotrimazole and miconazole. PMID:24159302

  8. Generation and characterization of transgenic plum lines expressing the Gastrodia anti-fungal protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Gastrodia anti-fungal protein (GAFP) is a monocot mannose-binding plant lectin isolated from the Asiatic orchid Gastrodia elata. This lectin has provided documented disease resistance in transgenic tobacco and cotton against several root diseases, but it's potential to confer disease resistance...

  9. Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Candidiasis and cryptococcosis are diseases of widening global incidence as a result of increasing immunosuppressive disorders, such as AIDS. An enduring problem for treatment of these mycoses is recurrent development of resistance to introduced antifungal drugs. We examined the potential for enhan...

  10. Broad-spectrum antifungal-producing lactic acid bacteria and their application in fruit models.

    PubMed

    Crowley, Sarah; Mahony, Jennifer; van Sinderen, Douwe

    2013-07-01

    A large-scale screen of some 7,000 presumptive lactic acid bacteria (LAB), isolated from animal, human, or plant origin, identified 1,149 isolates with inhibitory activity against the food-spoilage mould Penicillium expansum. In excess of 500 LAB isolates were subsequently identified to produce a broad spectrum of activity against P. expansum, Penicillium digitatum, Penicillium notatum, Penicillium roqueforti, Rhizopus stolonifer, Fusarium culmorum, Aspergillus fumigatus and Rhodotorula mucilaginosa. Partial 16S rRNA sequencing of 94 broad spectrum isolates revealed that the majority of antifungal producers were strains of Lactobacillus plantarum. The remaining population was composed of Weissella confusa and Pediococcus pentosaceous isolates. Characterization of six selected broad-spectrum antifungal LAB isolates revealed that antifungal activity is maximal at a temperature of 30 °C, a pH of 4.0 and is stable across a variety of salt concentrations. The antifungal compound(s) was shown to be neither proteinaceous nor volatile in nature. P. pentosaceous 54 was shown to have protective properties against P. expansum spoilage when applied in pear, plum and grape models, therefore representing an excellent candidate for food-related applications. PMID:23160868

  11. In vitro effectiveness of antifungal lock solutions on catheters infected with Candida species.

    PubMed

    Öncü, Serkan

    2011-10-01

    The antibiotic lock technique involves filling the catheter lumen with an antibiotic solution and allowing it to dwell for sufficient time to sterilize the infected device. However, antifungal therapy for treating catheter-related fungal infection in this setting is unknown. In this study, the effectiveness of the commercially available antifungal drugs, which are commonly used in candidemia, were assessed in an in vitro antibiotic lock model. Amphotericin B, caspofungin, fluconazole, itraconazole, and voriconazole were used as lock solutions against catheters infected with slime-forming Candida albicans and Candida parapsilosis. Infected catheters were exposed to each of the antifungal lock solution (300-, 500- and 1,000-fold MIC) for 1, 3, 5, and 7 days. The presence of the remaining Candida in the catheter was evaluated quantitatively. Among the antifungal agents, amphotericin B and caspofungin lock solutions decreased the yeast colony count significantly from baseline starting on the first day of treatment (P < 0.001). Significant decrease in the colony count continued, and the catheters were completely sterile at the fifth day. Fluconazole, itraconazole, and voriconazole lock solutions failed to sterilize the catheters, and the numbers of yeast colonies were >10(5) at the end of the study. In summary, amphotericin B and caspofungin appear to have unique activities against Candida-infected catheters. It seems that one of these drugs may permit the retention of an affected intravascular catheter by sterilizing it in a few days. PMID:21327934

  12. Eupatorium capillifolium essential oil: chemical composition antifungal activity and insecticidal activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural plant extracts often contain compounds that are useful in pest management applications. The essential oil of Eupatorium capillifolium (dog-fennel) was investigated for antifungal and insecticidal activities. Essential oil obtained by hydrodistillation of aerial parts was analyzed by gas chro...

  13. Optimization for the Production of Surfactin with a New Synergistic Antifungal Activity

    PubMed Central

    Liu, Mei; Dai, Huanqin; Song, Fuhang; Yu, Zhenyan; Wang, Shujin; Hu, Jiangchun; Kokare, Chandrakant R.; Zhang, Lixin

    2012-01-01

    Background Two of our long term efforts are to discover compounds with synergistic antifungal activity from metabolites of marine derived microbes and to optimize the production of the interesting compounds produced by microorganisms. In this respect, new applications or mechanisms of already known compounds with a high production yield could be continually identified. Surfactin is a well-known lipopeptide biosurfactant with a broad spectrum of antimicrobial and antiviral activity; however, there is less knowledge on surfactin’s antifungal activity. In this study, we investigated the synergistic antifungal activity of C15-surfactin and the optimization of its production by the response surface method. Methodology/Principal Findings Using a synergistic antifungal screening model, we found that the combination of C15-surfactin and ketoconazole (KTC) showed synergistic antifungal effect on Candida albicans SC5314 when the concentrations of C15-surfactin and KTC were 6.25 µg/mL and 0.004 µg/mL, respectively. These concentrations were lower than their own efficient antifungal concentrations, which are >100 µg/mL and 0.016 µg/mL, respectively. The production of C15-surfactin from Bacillus amyloliquefaciens was optimized by the response surface methodology in shaker flask cultivation. The Plackett-Burman design found sucrose, ammonium nitrate and NaH2PO4.2H2O to have significant effects on C15-surfactin production. The optimum values of the tested variables were 21.17 g/L sucrose, 2.50 g/L ammonium nitrate and 11.56 g/L NaH2PO4·2H2O. A production of 134.2 mg/L, which were in agreement with the prediction, was observed in a verification experiment. In comparison to the production of original level (88.6 mg/L), a 1.52-fold increase had been obtained. Conclusion/Significance This work first found that C15-surfactin was an efficient synergistic antifungal agent, and demonstrated that response surface methodology was an effective method to improve the production of C15-surfactin. PMID:22629294

  14. Chemical composition and antifungal activity of essential oils from different tissues of Japanese Cedar (Cryptomeria japonica).

    PubMed

    Cheng, Sen-Sung; Lin, Huang-Yuan; Chang, Shang-Tzen

    2005-02-01

    In this study antifungal activities of essential oils from different tissues of Japanese cedar (Cryptomeria japonica D. Don) against four wood decay fungi and six tree pathogenic fungi were investigated. In addition, the yields of essential oils obtained by water distillation were compared and their constituents determined by GC-MS analyses. The yield of essential oils from four tissues of Japanese cedar is in the decreasing order of leaf (27.38 mL/kg) > bark (6.31 mL/kg) > heartwood (3.80 mL/kg) > sapwood (1.27 mL/kg). Results obtained from the antifungal tests demonstrate that the essential oil of Japanese cedar heartwood used against Laetiporus sulphureus and Trametes versicolor and sapwood essential oil used against L. sulphureus had strong antifungal activities at 500 mug/mL, with IC(50) values of 39, 91, and 94 microg/mL, respectively. Besides, the essential oils of Japanese cedar heartwood used against Rhizoctonia solani, Collectotrichum gloeosporioides, Fusarium solani, and Ganoderma australe had strong antifungal activities at 500 microg/mL, with IC(50) values of 65, 80, 80, and 110 microg/mL, respectively. GC-MS analyses showed that the sesquiterpene hydrocarbon compounds dominate in the essential oil from Japanese cedar heartwood, amounting to a total percentage of 82.56%, with the major compounds of delta-cadinene (18.60%), isoledene (12.41%), and gamma-muurolene (11.82%). It is proposed that the excellent antifungal activities of Japanese cedar heartwood essential oils might correlate with the presence of these compounds. PMID:15686410

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

    SciTech Connect

    Palicz, Zoltán; Jenes, Ágnes; Gáll, Tamás; Miszti-Blasius, Kornél; Kollár, Sándor; Kovács, Ilona; Emri, Miklós; Márián, Teréz; Leiter, Éva; Pócsi, István; Cs?sz, Éva; Kalló, Gerg?; Heged?s, Csaba; Virág, László; Csernoch, László; Szentesi, Péter

    2013-05-15

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

  16. A study to evaluate the price control of antifungal medicines and its practical applicability

    PubMed Central

    Sil, Amrita; Das, Nilay Kanti; Ghosh, Pramit; Datta, Pijush Kanti; Islam, Chowdhury Nazrul; Tripathi, Santanu Kumar

    2012-01-01

    Background: Superficial fungal infections are common and treatment imposes economic burden on the patients. Government of India had introduced price control over griseofulvin and tolnaftate in 1995; however, this measure can only benefit the needy if the policy is harmonized with the health-care service provider, that is, dermatologists. The aim of this study was to evaluate the existing Government mechanisms over price control of antifungal medications and its reach to the people-in-need. Materials and Methods: A questionnaire-based, cross-sectional study was carried out over a period of 6 months. Questionnaire was mailed to members of a state branch of Indian Association of Dermatologists, Venereologists, and Leprologists. Responses reaching investigators within 2 months from the date of mailing were finally analyzed. Results: Among 93 (41.33%) respondents, only 6 (6.5%) were aware of existing price control over griseofulvin but none about tolnaftate. Thirty-nine (41.9%) respondents were in favor of introducing price control on terbinafine and 42 (45.2%) for itraconazole. The topically preferred antifungals were primarily azoles and terbinafine, while among systemic antifungals, dermatologists mostly preferred fluconazole and terbinafine. The choice of antifungals by the dermatologists matched with the evidence-based dermatology data. Conclusion: Currently, price-controlled antifungal drugs are less commonly used by practitioners. Although the dermatologists favor price control, the initiative undertaken by the Government has not reached them. This shows the need to bridge the gap between policy makers and health-care service providers to help the ailing population. PMID:23248398

  17. Antifungal activity and mechanism of fengycin in the presence and absence of commercial surfactin against Rhizopus stolonifer.

    PubMed

    Tao, Yang; Bie, Xiao-mei; Lv, Feng-xia; Zhao, Hai-zhen; Lu, Zhao-xin

    2011-02-01

    The antifungal activity and mechanism of fengycin in the presence and absence of commercial surfactin against Rhizopus stolonifer were investigated. The MIC (minimal inhibitory concentration) of fengycin without commercial surfactin added was 0.4 mg/ml while the MIC of fengycin with commercial surfactin added was 2.0 mg/ml. Fengycin acted on cell membrane and cellular organs and inhibited DNA synthesis. The antifungal effect of fengycin was reduced after commercial surfactin was added. All these results suggest that the fungal cell membrane may be the primary target of fengycin action and commercial surfactin may reduce the antifungal activity of fengycin. PMID:21369992

  18. Synthesis and antifungal evaluation of head-to-head and head-to-tail bisamidine compounds.

    PubMed

    Nguyen, Son T; Kwasny, Steven M; Ding, Xiaoyuan; Williams, John D; Peet, Norton P; Bowlin, Terry L; Opperman, Timothy J

    2015-09-01

    Herein, we describe the antifungal evaluation of 43 bisamidine compounds, of which 26 are new, having the scaffold [Am]-[HetAr]-[linker]-[HetAr]-[Am], in which [Am] is a cyclic or acyclic amidine group, [linker] is a benzene, pyridine, pyrimidine, pyrazine ring, or an aliphatic chain of two to four carbon, and [HetAr] is a 5,6-bicyclic heterocycle such as indole, benzimidazole, imidazopyridine, benzofuran, or benzothiophene. In the head-to-head series the two [HetAr] units are oriented such that the 5-membered rings are connected through the linker, and in the head-to-tail series, one of the [HetAr] systems is connected through the 6-membered ring; additionally, in some of the head-to-tail compounds, the [linker] is omitted. Many of these compounds exhibited significant antifungal activity against Candida albicans, Candida krusei, Candida glabrata, Candida parapsilosis, and Cryptococcus neoformans (MIC ? 4 ?g/ml). The most potent compounds, for example, P10, P19 and P34, are comparable in antifungal activities to amphotericin B (MIC 0.125 ?g/ml). They exhibited rapid fungicidal activity (>3 log10 decrease in cfu/ml in 4h) at concentrations equivalent to 4× the MIC in time kill experiments. The bisamidines strongly inhibited DNA, RNA and cell wall biosynthesis in C. albicans in macromolecular synthesis assays. However, the half-maximal inhibitory concentration for DNA synthesis was approximately 30-fold lower than those for RNA and cell wall biosynthesis. Fluorescence microscopy of intact cells of C. albicans treated with a bisamidine exhibited enhanced fluorescence in the presence of DNA, demonstrating that the bisamidine was localized to the nucleus. The results of this study show that bisamidines are potent antifungal agents with rapid fungicidal activity, which is likely to be the result of their DNA-binding activity. Although it was difficult to obtain a broad-spectrum antifungal compound with low cytotoxicity, some of the compounds (e.g., P9, P14 and P43) exhibited favorable CC50 values against HeLa cells and maintained considerable antifungal activity. PMID:26209266

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

    PubMed Central

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

    2013-01-01

    Purpose. Fusarium, Aspergillus, and Dematiaceous are the most common fungal species causing keratitis in tropical countries. Herein we report a prospective study on fungal keratitis caused by these three fungal species. Methodology. A prospective investigation was undertaken to evaluate eyes with presumed fungal keratitis. All the fungal isolates (n = 73) obtained from keratitis infections were identified using morphological and microscopic characters. Molecular identification using sequencing of the ITS region and antifungal susceptibility tests using microdilution method were done. The final clinical outcome was evaluated in terms of the time taken for resolution of keratitis and the final visual outcome. The results were analyzed after segregating the cases into three groups, namely, Fusarium, Aspergillus, and Dematiaceous keratitis. Results. Diagnosis of fungal keratitis was established in 73 (35.9%) cases out of 208 cases. The spectra of fungi isolated were Fusarium spp. (26.6%), Aspergillus spp. (21.6%), and Dematiaceous fungi (11.6%). The sequence of the ITS region could identify the Fusarium and Aspergillus species at the species complex level, and the Dematiaceous isolates were accurately identified. Using antifungal agents such as fluconazole, natamycin, amphotericin B, and itraconazole, the minimum inhibitory concentrations (MICs) for Fusarium spp. were >32??g/mL, 4–8??g/mL, 0.5–1??g/mL, and >32??g/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

  20. The in vitro antifungal activity of sudanese medicinal plants against Madurella mycetomatis, the eumycetoma major causative agent.

    PubMed

    Elfadil, Hassabelrasoul; Fahal, Ahmed; Kloezen, Wendy; Ahmed, Elhadi M; van de Sande, Wendy

    2015-03-01

    Eumycetoma is a debilitating chronic inflammatory fungal infection that exists worldwide but it is endemic in many tropical and subtropical regions. The major causative organism is the fungus Madurella mycetomatis. The current treatment of eumycetoma is suboptimal and characterized by low cure rate and high recurrence rates. Hence, an alternative therapy is needed to address this. Here we determined the antifungal activity of seven Sudanese medicinal plant species against Madurella mycetomatis. Of these, only three species; Boswellia papyrifera, Acacia nubica and Nigella sativa, showed some antifungal activity against M. mycetomatis and were further studied. Crude methanol, hexane and defatted methanol extracts of these species were tested for their antifungal activity. B. papyrifera had the highest antifungal activity (MIC50 of 1 ug/ml) and it was further fractionated. The crude methanol and the soluble ethyl acetate fractions of B. papyrifera showed some antifungal activity. The Gas-Liquid-Chromatography hybrid Mass-Spectrophotometer analysis of these two fractions showed the existence of beta-amyrin, beta-amyrone, beta-Sitosterol and stigmatriene. Stigmatriene had the best antifungal activity, compared to other three phytoconstituents, with an MIC-50 of 32 ?g/ml. Although the antifungal activity of the identified phytoconstituents was only limited, the antifungal activity of the complete extracts is more promising, indicating synergism. Furthermore these plant extracts are also known to have anti-inflammatory activity and can stimulate wound-healing; characteristics which might also be of great value in the development of novel therapeutic drugs for this chronic inflammatory disease. Therefore further exploration of these plant species in the treatment of mycetoma is encouraging. PMID:25768115

  1. The In Vitro Antifungal Activity of Sudanese Medicinal Plants against Madurella mycetomatis, the Eumycetoma Major Causative Agent

    PubMed Central

    Elfadil, Hassabelrasoul; Fahal, Ahmed; Kloezen, Wendy; Ahmed, Elhadi M.; van de Sande, Wendy

    2015-01-01

    Eumycetoma is a debilitating chronic inflammatory fungal infection that exists worldwide but it is endemic in many tropical and subtropical regions. The major causative organism is the fungus Madurella mycetomatis. The current treatment of eumycetoma is suboptimal and characterized by low cure rate and high recurrence rates. Hence, an alternative therapy is needed to address this. Here we determined the antifungal activity of seven Sudanese medicinal plant species against Madurella mycetomatis. Of these, only three species; Boswellia papyrifera, Acacia nubica and Nigella sativa, showed some antifungal activity against M. mycetomatis and were further studied. Crude methanol, hexane and defatted methanol extracts of these species were tested for their antifungal activity. B. papyrifera had the highest antifungal activity (MIC50 of 1 ug/ml) and it was further fractionated. The crude methanol and the soluble ethyl acetate fractions of B. papyrifera showed some antifungal activity. The Gas-Liquid-Chromatography hybrid Mass-Spectrophotometer analysis of these two fractions showed the existence of beta-amyrin, beta-amyrone, beta-Sitosterol and stigmatriene. Stigmatriene had the best antifungal activity, compared to other three phytoconstituents, with an MIC-50 of 32 ?g/ml. Although the antifungal activity of the identified phytoconstituents was only limited, the antifungal activity of the complete extracts is more promising, indicating synergism. Furthermore these plant extracts are also known to have anti-inflammatory activity and can stimulate wound-healing; characteristics which might also be of great value in the development of novel therapeutic drugs for this chronic inflammatory disease. Therefore further exploration of these plant species in the treatment of mycetoma is encouraging. PMID:25768115

  2. In vitro antifungal activity of pneumocandin L-743,872 against a variety of clinically important molds.

    PubMed Central

    Del Poeta, M; Schell, W A; Perfect, J R

    1997-01-01

    The in vitro activity of the new antifungal drug pneumocandin L-743,872 against 55 isolates of clinically important molds was examined by an adapted macrobroth dilution method for yeasts. Pneumocandin L-743,872 exhibited in vitro antifungal activity against Alternaria sp., Aspergillus flavus, Aspergillus fumigatus, Curvularia lunata, Exophiala jeanselmei, Fonsecaea pedrosoi, Paecilomyces variotii, and Scedosporium apiospermum. The drug appeared to lack significant in vitro inhibitory activity against Fusarium oxysporum, Fusarium solani, Rhizopus arrhizus, Paecilomyces lilacinus, and Scedosporium prolificans. PMID:9257774

  3. Antifungal activity, biofilm-controlling effect, and biocompatibility of poly(N-vinyl-2-pyrrolidinone)-grafted denture materials

    PubMed Central

    Sun, Xinbo; Cao, Zhengbing; Yeh, Chih-Ko; Sun, Yuyu

    2013-01-01

    Colonization and biofilm-formation of Candida species on denture surfaces cause Candida-associated denture stomatitis (CADS), a common, recurring disease affecting up to 67% of denture wearers. We developed poly(N-vinyl-2-pyrrolidinone)-grafted denture materials that can be repeatedly recharged with various antifungal drugs to achieve long-term antifungal and biofilm-controlling effects. The monomer, N-vinyl-2-pyrrolidinone (NVP), was grafted onto poly(methyl methacrylate) denture resins through plasma-initiated grafting polymerization. The physical properties and biocompatibility of the resulting resins were not negatively affected by the presence of up to 7.92% of grafted poly (N-vinyl-2-pyrrolidinone) (PNVP). Miconazole and chlorhexidine digluconate (CD) were used as model antifungal drugs. PNVP grafting significantly increased the drug absorption capability of the resulting denture materials. Further, the new materials showed sustained drug release and provided antifungal effects for weeks (in the case of CD) to months (in the case of miconazole). The drug-depleted resins could be recharged with the same or a different class of antifungal drug to further extend antifungal duration. If needed, drugs on the PNVP-grafted denture materials could be “washed out” (quenched) by treating with PNVP aqueous solutions to stop drug release. These results point to great potentials of the new materials in controlling biofilm-formation in a wide range of device-related applications. PMID:23708753

  4. Antifungal activity of extracts from Cynomorium coccineum growing wild in Sardinia island (Italy).

    PubMed

    Gonçalves, Maria José; Piras, Alessandra; Porcedda, Silvia; Marongiu, Bruno; Falconieri, Danilo; Cavaleiro, Carlos; Rescigno, Antonio; Rosa, Antonella; Salgueiro, Ligia

    2015-12-01

    Cynomorium coccineum L. is a non-photosynthetic plant, spread over Mediterranean countries, amply used in traditional medicine. The aim of this study was to evaluate for the first time the antifungal activity of its extracts. The antifungal activity was evaluated using the macrodilution method against Candida spp., Cryptococcus neoformans and dermatophyte strains. The methanolic extract was very active against C. neoformans, Candida guilliermondii and Candida krusei, with minimal inhibitory concentrations (MIC) values of 0.025 mg/mL. This extract is more active than fluconazole against C. krusei H9. The influence of methanolic extract on the dimorphic transition in Candida albicans was also studied through the germ tube inhibition assay. More than 60% of filamentation was inhibited at a concentration of 1/4 MIC. These results are preliminary and further studies are needed to an eventual use of C. coccineum methanolic extract in the treatments of candidiasis and cryptococcosis. PMID:25598435

  5. In vitro activities of a wide panel of antifungal drugs against various Scopulariopsis and Microascus species.

    PubMed

    Skóra, Magdalena; Bulanda, Ma?gorzata; Jagielski, Tomasz

    2015-09-01

    The in vitro activities of 11 antifungal drugs against 68 Scopulariopsis and Microascus strains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 ?g/ml and 0.125 to 16 ?g/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50 and MEC50 were 1 µg/ml for both drugs, whereas the MIC90 and MEC90 were 4 µg/ml and 16 µg/ml, respectively. PMID:26100698

  6. Antifungal Activity of Selected Indigenous Pseudomonas and Bacillus from the Soybean Rhizosphere

    PubMed Central

    León, M.; Yaryura, P. M.; Montecchia, M. S.; Hernández, A. I.; Correa, O. S.; Pucheu, N. L.; Kerber, N. L.; García, A. F.

    2009-01-01

    The purpose of this study was to isolate and select indigenous soil Pseudomonas and Bacillus bacteria capable of developing multiple mechanisms of action related to the biocontrol of phytopathogenic fungi affecting soybean crops. The screening procedure consisted of antagonism tests against a panel of phytopathogenic fungi, taxonomic identification, detection by PCR of several genes related to antifungal activity, in vitro detection of the antifungal products, and root colonization assays. Two isolates, identified and designated as Pseudomonas fluorescens BNM296 and Bacillus amyloliquefaciens BNM340, were selected for further studies. These isolates protected plants against the damping-off caused by Pythium ultimum and were able to increase the seedling emergence rate after inoculation of soybean seeds with each bacterium. Also, the shoot nitrogen content was higher in plants when seeds were inoculated with BNM296. The polyphasic approach of this work allowed us to select two indigenous bacterial strains that promoted the early development of soybean plants. PMID:20016811

  7. Effect of chitosan and its derivatives as antifungal and preservative agents on postharvest green asparagus.

    PubMed

    Qiu, Miao; Wu, Chu; Ren, Gerui; Liang, Xinle; Wang, Xiangyang; Huang, Jianying

    2014-07-15

    The antifungal activity and effect of high-molecular weight chitosan (H-chitosan), low-molecular weight chitosan (L-chitosan) and carboxymethyl chitosan (C-chitosan) coatings on postharvest green asparagus were evaluated. L-chitosan and H-chitosan efficiently inhibited the radial growth of Fusarium concentricum separated from postharvest green asparagus at 4 mg/ml, which appeared to be more effective in inhibiting spore germination and germ tube elongation than that of C-chitosan. Notably, spore germination was totally inhibited by L-chitosan and H-chitosan at 0.05 mg/ml. Coated asparagus did not show any apparent sign of phytotoxicity and maintained good quality over 28 days of cold storage, according to the weight loss and general quality aspects. Present results inferred that chitosan could act as an attractive preservative agent for postharvest green asparagus owing to its antifungal activity and its ability to stimulate some defense responses during storage. PMID:24594161

  8. Antifungal Substances from Streptomyces sp. A3265 Antagonistic to Plant Pathogenic Fungi.

    PubMed

    Van Minh, Nguyen; Woo, E-Eum; Kim, Ji-Yul; Kim, Dae-Won; Hwang, Byung Soon; Lee, Yoon-Ju; Lee, In-Kyoung; Yun, Bong-Sik

    2015-09-01

    In a previous study, we identified a Streptomyces sp., A3265, as exhibiting potent antifungal activity against various plant pathogenic fungi, including Botrytis cinerea, Colletotrichum gloeosporioides, and Rhizoctonia solani. This strain also exhibited a biocontrolling effect against ginseng root rot and damping-off disease, common diseases of ginseng and other crops. In this study, we isolated two antifungal substances responsible for this biocontrolling effect via Diaion HP-20 and Sephadex LH-20 column chromatography, medium pressure liquid chromatography, and high-performance liquid chromatography. These compounds were identified as guanidylfungin A and methyl guanidylfungin A by spectroscopic methods. These compounds exhibited potent antimicrobial activity against various plant pathogenic fungi as well as against bacteria. PMID:26539051

  9. Anti-fungal activity of Citrus reticulata Blanco essential oil against Penicillium italicum and Penicillium digitatum.

    PubMed

    Tao, Nengguo; Jia, Lei; Zhou, Haien

    2014-06-15

    The chemical composition of Citrus reticulata Blanco essential oil was analysed using GC/MS. Monoterpene hydrocarbons (C10H16) constituted the majority (88.96%, w/w) of the total oil. The oils dose-dependently inhibited Penicillium italicum and Penicillium digitatum. The anti-fungal activity of the oils against P. italicum was attributed to citronellol, octanal, citral, decanal, nonanal, ?-pinene, linalool, and ?-terpinene, whereas anti-fungal activity against P. digitatum is attributed to octanal, decanal, nonanal, limonene, citral, ?-terpinene, linalool, and ?-terpineol. The oils altered the hyphal morphology of P. italicum and P. digitatum by causing loss of cytoplasm and distortion of the mycelia. The oils significantly altered extracellular conductivity, the release of cell constituents, and the total lipid content of P. italicum and P. digitatum. The results suggest that C. reticulata Blanco essential oils generate cytotoxicity in P. italicum and P. digitatum by disrupting cell membrane integrity and causing the leakage of cell components. PMID:24491729

  10. Antifungal activity of thionated analogues of Nva-FMDP and Lys-Nva-FMDP.

    PubMed

    Nowak-Jary, Julia; Andruszkiewicz, Ryszard

    2009-01-01

    The antifungal activity of synthetic endothiopeptdides, i.e. Nva(psi)[CSNH]-FMDP and Lys(psi)[CSNH]-Nva(psi)[CSNH]-FMDP was studied in medium containing blood serum, against selected Candida strains; Candida albicans Gu4 (fluconazole sensitive), C. albicans Gu5 (fluconazole resistant), C. albicans ATCC 10231, Candida krusei DSM 6128 and Candida parapsilosis DSM 5784. Although thiopeptide bonds in the tested peptides increased their stability in blood serum, their antifungal activity, however, drastically decreased in comparison with the peptides containing non-modified peptide bonds. Moreover, the inhibitory activity towards glucosamine-6-phosphate synthase of thionated synthetic analogue of FMDP was performed. The thiopeptdide bond also influenced its inhibitory properties against enzyme from C. albicans. PMID:20380139

  11. Processing of ?-chitin nanofibers by dynamic high pressure homogenization: characterization and antifungal activity against A. niger.

    PubMed

    Salaberria, Asier M; Fernandes, Susana C M; Diaz, Rene Herrera; Labidi, Jalel

    2015-02-13

    Chitin nano-objects become more interesting and attractive material than native chitin because of their usable form, low density, high surface area and promising mechanical properties. This work suggests a straightforward and environmentally friendly method for processing chitin nanofibers using dynamic high pressure homogenization. This technique proved to be a remarkably simple way to get ?-chitin into ?-chitin nanofibers from yellow lobster wastes with a uniform width (bellow 100 nm) and high aspect ratio; and may contributes to a major breakthrough in chitin applications. Moreover, the resulting ?-chitin nanofibers were characterized and compared with native ?-chitin in terms of chemical and crystal structure, thermal degradation and antifungal activity. The biological assays highlighted that the nano nature of chitin nanofibers plays an important role in the antifungal activity against Aspergillus niger. PMID:25458302

  12. Antipodal crambescin A2 homologues from the marine sponge Pseudaxinella reticulata. Antifungal structure-activity relationships.

    PubMed

    Jamison, Matthew T; Molinski, Tadeusz F

    2015-03-27

    Investigation of antifungal natural products from the marine sponge Pseudaxinella reticulata from the Bahamas led to the discovery of new crambescin homologues (1, 2) and enantiomers (3, 4) of known natural products. The cyclic-guanidine structures were solved through analysis of 2D NMR, MS-MS, and CD data. The absolute configurations of 1-4 were established as 13R-opposite of known homologues reported from Crambe crambe obtained from the Mediterranean Sea-by comparison of their CD spectra with predicted Cotton effects obtained from DFT calculations. Antifungal activities of 1-4 against the pathogenic strains Candida albicans and Cryptococcus sp. were observed to correlate potency (MIC50 and MIC90) with the length of the alkyl side chain. PMID:25738226

  13. Chemical composition, antifungal and antibacterial activity of the essential oil of Chamaecyparis nootkatensis from Spain.

    PubMed

    Palá-Paúl, Jesús; Usano-Alemany, Jaime; Granda, Elena; Soria, Ana-Cristina

    2009-07-01

    The chemical composition of the oil of Chamaecyparis nootkatensis (D. Don) Spach. has been analysed by gas chromatography (GC) and gas chromatography coupled to mass spectrometry (GC-MS). A total of 34 compounds were identified representing more than 90% of the total oil. The oil was richer in monoterpenes than in sesquiterpenes, the major constituents being limonene (53.2%), 6-3-carene (21.0%) and a-pinene (12.2%). The antibacterial and antifungal activities of the oil were also tested against Candida albicans, Bacillus subtilis, Enterobacter aerogenes, Enterococcus faecalis, Escherichia coli, Micrococcus luteus, Pseudomonas aeruginosa, Salmonella sp. and Serratia marcescens. Only two of these, Bacillus subtilis and Candida albicans, were sensitive to the treatment, inhibition zones of 11 and 14 mm diameter being obtained, respectively. As far as we know, this is the first report of the antifungal and antibacterial activity of this species. PMID:19731613

  14. Antifungal Substances from Streptomyces sp. A3265 Antagonistic to Plant Pathogenic Fungi

    PubMed Central

    Van Minh, Nguyen; Woo, E-Eum; Kim, Ji-Yul; Kim, Dae-Won; Hwang, Byung Soon; Lee, Yoon-Ju; Lee, In-Kyoung

    2015-01-01

    In a previous study, we identified a Streptomyces sp., A3265, as exhibiting potent antifungal activity against various plant pathogenic fungi, including Botrytis cinerea, Colletotrichum gloeosporioides, and Rhizoctonia solani. This strain also exhibited a biocontrolling effect against ginseng root rot and damping-off disease, common diseases of ginseng and other crops. In this study, we isolated two antifungal substances responsible for this biocontrolling effect via Diaion HP-20 and Sephadex LH-20 column chromatography, medium pressure liquid chromatography, and high-performance liquid chromatography. These compounds were identified as guanidylfungin A and methyl guanidylfungin A by spectroscopic methods. These compounds exhibited potent antimicrobial activity against various plant pathogenic fungi as well as against bacteria. PMID:26539051

  15. HM17, a new polyene antifungal antibiotic produced by a new strain of Spirillospora.

    PubMed

    Hacčne, H; Kebir, K; Othmane, D S; Lefebvre, G

    1994-11-01

    An antifungal antibiotic (HM17) was obtained from a new isolate classified to the genus Spirillospora on the basis of its chemical and morphological properties. On solid media this antibiotic strongly inhibited the growth of strains of Fusarium oxysporum formae speciales albedinis, Botrytis cinerea, Gaeumaniomyces graminis and several other fungi known to be plant and human pathogens. Antifungal activity in culture collection strains of Spirillospora has not so far been reported. The u.v. absorption spectrum and physico-chemical characteristics place HM17 in the methylpentaene sub-group of polyene macrolides. HM17 is different from other known methylpentaenes. This is the first report of polyene production by a Spirillospora. PMID:8002474

  16. Synthesis of biocontrol macromolecules by derivative of chitosan with surfactin and antifungal evaluation.

    PubMed

    Yuan, Bo; Xu, Pei-Yuan; Zhang, Yue-Ji; Wang, Pei-Pei; Yu, Hong; Jiang, Ji-Hong

    2014-05-01

    A derivative of chitosan was prepared with chitosan and ?-cyclodextrins, which was synthesized by the immobilization reaction, as a carrier to adsorb surfactin produced from Bacillus amyloliquefaciens and got biological macromolecules. The antifungal activity against three sapstain fungi by a combination of macromolecules was tested. The results showed that the macromolecules inhibited the mycelium growth of sapstain fungi Lasiodiplodia rubropurpurea, L. crassispora, and L. theobromae by about 73.22%, 76.72%, and 70.22%, respectively. The macromolecules were relatively thermally stable with more than 50% of the antifungal activity even after being held at 121°C for 30 min. Meanwhile, the activity of the macromolecules remained more than 55% at a pH value ranging from 4 to 12. The macromolecules were resistant to hydrolysis by most protein-denaturing detergents and other enzymes. The results indicated the macromolecules might provide an alternative bioresource for the bio-control of sapstain. PMID:24530369

  17. Molecular Characterization and In Vitro Antifungal Susceptibility of 316 Clinical Isolates of Dermatophytes in Iran.

    PubMed

    Ansari, Saham; Hedayati, Mohammad T; Zomorodian, Kamiar; Pakshir, Keyvan; Badali, Hamid; Rafiei, Abdollah; Ravandeh, Mostafa; Seyedmousavi, Seyedmojtaba

    2016-02-01

    Dermatophytosis is a common mycotic infection of the skin, nail, and hair, associated with major public health concern worldwide. Various species of dermatophytes show significant differences in susceptibility to antifungals. Here, we present the antifungal susceptibility of a large collection of molecularly identified dermatophyte isolates obtained from tropical region of south of Iran. A total of 9485 patients clinically suspected to have cutaneous fungal infections were examined. Dermatophytosis was confirmed in 1502 cases by direct microscopy and culture. Three hundred and sixteen isolates recovered in culture were identified to species level using PCR sequencing of ITS region and RFLP. Tinea corporis was the most prevalent type of clinical manifestation (35.2 %), followed by tinea cruris (17 %), tinea capitis (12.8 %), tinea pedis (11.3 %), tinea manuum (11 %), tinea unguium (6.9 %), and tinea barbae (5.8 %). Trichophyton interdigitale was the most common isolate (49.36 %), followed by Trichophyton rubrum (18.98 %), Epidermophyton floccosum (13.29 %), Microsporum canis (9.17 %), Arthroderma benhamiae (T. anamorph of A. benhamiae; 5.38 %), and Trichophyton tonsurans (3.79 %). Overall, irrespective of the geographical region, terbinafine was the most potent antifungal against all isolates, with an MIC range of 0.002-0.25 ?g/mL, followed by itraconazole (0.004-0.5 ?g/mL), griseofulvin (0.125-8 ?g/mL), and fluconazole (4-128 ?g/mL). Analysis of our data revealed a significant increase in the frequency of A.benhamiae, which definitely warrants further investigation to explore source of this infection in south of Iran. Moreover, terbinafine was the most effective antifungal against all isolates, in vitro. PMID:26369643

  18. In Vitro Susceptibility Profiles of Eight Antifungal Drugs against Clinical and Environmental Strains of Phaeoacremonium.

    PubMed

    Badali, Hamid; Khodavaisy, Sadegh; Fakhim, Hamed; de Hoog, G Sybren; Meis, Jacques F; Chowdhary, Anuradha

    2015-12-01

    In vitro susceptibilities of a worldwide collection of molecularly identified Phaeoacremonium strains (n = 43) belonging to seven species and originating from human and environmental sources were determined for eight antifungal drugs. Voriconazole had the lowest geometric mean MIC (0.35 ?g/ml), followed by posaconazole (0.37 ?g/ml), amphotericin B (0.4 ?g/ml), and isavuconazole (1.16 ?g/ml). Caspofungin, anidulafungin, fluconazole, and itraconazole had no activity. PMID:26369976

  19. Comparison of the in vitro activities of newer triazoles and established antifungal agents against Trichophyton rubrum.

    PubMed

    Deng, Shuwen; Zhang, Chao; Seyedmousavi, Seyedmojtaba; Zhu, Shuang; Tan, Xin; Wen, Yiyang; Huang, Xin; Lei, Wenzhi; Zhou, Zhaojing; Fang, Wenjie; Shen, Shuaishuai; Deng, Danqi; Pan, Weihua; Liao, Wanqing

    2015-07-01

    One hundred eleven clinical Trichophyton rubrum isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26 mg/liter; griseofulvin, 1.65 mg/liter; and fluconazole, 2.12 mg/liter. PMID:25896691

  20. Antifungal activity of compounds extracted from Cortex Pseudolaricis against Colletotrichum gloeosporioides.

    PubMed

    Zhang, Jing; Yan, Li-Ting; Yuan, En-Lin; Ding, Hai-Xin; Ye, Huo-Chun; Zhang, Zheng-Ke; Yan, Chao; Liu, Ying-Qian; Feng, Gang

    2014-05-28

    Cortex Pseudolaricis is the root bark of Pseudolarix amabilis Rehder, found only in China, and has been widely used in folk antifungal remedies in traditional Chinese medicine. In order to find the natural antifungal agents against mango anthracnose, eight compounds, namely pseudolaric acid A (1), ethyl pseudolaric acid B (2), pseudolaric acid B (3), pseudolaric acid B-O-?-d-glucoside (4), piperonylic acid (5), propionic acid (6), 3-hydroxy-4-methoxybenzoic acid (7), and 4-(3-formyl-5-methoxyphenyl) butanoic acid (8) were isolated from the ethanol extracts of Cortex Pseudolaricis by bioassay-guided fractionation and evaluated for in vitro antifungal activity against Colletotrichum gloeosporioides Penz. Results demonstrated that all of the eight compounds inhibited the mycelial growth of C. gloeosporioides at 5 ?g/mL. Among them, pseudolaric acid B and pseudolaric acid A showed the strongest inhibition with the EC50 values of 1.07 and 1.62 ?g/mL, respectively. Accordingly, both Pseudolaric acid B and Pseudolaric acid A highly inhibited spore germination and germ tube elongation of C. gloeosporioides. Dipping 100 ?g/mL pseudolaric acid B treatment exhibited more effective suppression on postharvest anthracnose in mango fruit when compared to the same concentration of carbendazim. Scanning electron microscopy observations revealed that pseudolaric acid B caused alterations in the hyphal morphology of C. gloeosporioides, including distortion, swelling, and collapse. Pseudolaric acid B caused the mycelial apexes to show an abnormal growth in dimensions with multiple ramifications in subapical expanded areas with irregular shape. These findings warrant further investigation into optimization of pseudolaric acid B to explore a potential antifungal agent for crop protection. PMID:24820992

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

    PubMed Central

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

    2014-01-01

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

  2. Lactobacillus amylovorus DSM 19280 as a novel food-grade antifungal agent for bakery products.

    PubMed

    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. PMID:21429613

  3. Melanin protects Paracoccidioides brasiliensis from the effects of antimicrobial photodynamic inhibition and antifungal drugs.

    PubMed

    Baltazar, Ludmila Matos; Werneck, Silvia Maria Cordeiro; Soares, Betânia Maria; Ferreira, Marcus Vinicius L; Souza, Danielle G; Pinotti, Marcos; Santos, Daniel Assis; Cisalpino, Patrícia Silva

    2015-07-01

    Paracoccidioidomycosis (PCM) is a public health concern in Latin America and South America that when not correctly treated can lead to patient death. In this study, the influence of melanin produced by Paracoccidioides spp. on the effects of treatment with antimicrobial photodynamic inhibition (aPI) and antifungal drugs was evaluated. aPI was performed using toluidine blue (TBO) as a photosensitizer and a 630-nm light-emitting diode (LED) light. The antifungals tested were itraconazole and amphotericin B. We evaluated the effects of each approach, aPI or antifungals, against nonmelanized and melanized yeast cells by performing susceptibility tests and by quantifying oxidative and nitrosative bursts during the experiments. aPI reduced nonmelanized cells by 3.0 log units and melanized cells by 1.3 log units. The results showed that melanization protects the fungal cell, probably by acting as a scavenger of nitric oxide and reactive oxygen species, but not of peroxynitrite. Melanin also increased the MICs of itraconazole and amphotericin B, and the drugs were fungicidal for nonmelanized and fungistatic for melanized yeast cells. Our study shows that melanin production by Paracoccidioides yeast cells serves a protective function during aPI and treatment with itraconazole and amphotericin B. The results suggest that melanin binds to the drugs, changing their antifungal activities, and also acts as a scavenger of reactive oxygen species and nitric oxide, but not of peroxynitrite, indicating that peroxynitrite is the main radical that is responsible for fungal death after aPI. PMID:25896704

  4. Fungal infection-related mortality versus total mortality as an outcome in trials of antifungal agents

    PubMed Central

    Due, Anne K; Johansen, Helle K; Gřtzsche, Peter C

    2006-01-01

    Background Disease specific mortality is often used as outcome rather than total mortality in clinical trials. This approach assumes that the classification of cause of death is unbiased. We explored whether use of fungal infection-related mortality as outcome rather than total mortality leads to bias in trials of antifungal agents in cancer patients. Methods As an estimate of bias we used relative risk of death in those patients the authors considered had not died from fungal infection. Our sample consisted of 69 trials included in four systematic reviews of prophylactic or empirical antifungal treatment in patients with cancer and neutropenia we have published previously. Results Thirty trials met the inclusion criteria. The trials comprised 6130 patients and 869 deaths, 220 (25%) of which were ascribed to fungal infection. The relative risk of death was 0.85 (95% CI 0.75–0.96) for total mortality, 0.57 (95% CI 0.44–0.74) for fungal mortality, and 0.95 (95% CI 0.82–1.09) for mortality among those who did not die from fungal infection. Conclusion We could not support the hypothesis that use of disease specific mortality introduces bias in antifungal trials on cancer patients as our estimate of the relative risk for mortality in those who survived the fungal infection was not increased. We conclude that it seems to be reliable to use fungal mortality as the primary outcome in trials of antifungal agents. Data on total mortality should be reported as well, however, to guard against the possible introduction of harmful treatments. PMID:16907965

  5. Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents.

    PubMed

    Wang, Yang; Sun, Wenbo; Zha, Shunqing; Wang, Huan; Zhang, Yalin

    2015-01-01

    Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, ąH-NMR, (13)C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3'-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC50 values of 0.88 and 0.97 ?g/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2', C-3' and C-4' positions of the phenyl ring, the presence of a halogen atom at the C-3'position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3' position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides. PMID:26633341

  6. Process Analysis of Variables for Standardization of Antifungal Susceptibility Testing of Nonfermentative Yeasts ?

    PubMed Central

    Zaragoza, Oscar; Mesa-Arango, Ana C.; Gómez-López, Alicia; Bernal-Martínez, Leticia; Rodríguez-Tudela, Juan Luis; Cuenca-Estrella, Manuel

    2011-01-01

    Nonfermentative yeasts, such as Cryptococcus spp., have emerged as fungal pathogens during the last few years. However, standard methods to measure their antifungal susceptibility (antifungal susceptibility testing [AST]) are not completely reliable due to the impaired growth of these yeasts in standard media. In this work, we have compared the growth kinetics and the antifungal susceptibilities of representative species of nonfermentative yeasts such as Cryptococcus neoformans, Cryptococcus gattii, Cryptococcus albidus, Rhodotorula spp., Yarrowia lipolytica, Geotrichum spp., and Trichosporon spp. The effect of the growth medium (RPMI medium versus yeast nitrogen base [YNB]), glucose concentration (0.2% versus 2%), nitrogen source (ammonium sulfate), temperature (30°C versus 35°C), shaking, and inoculum size (103, 104, and 105 cells) were analyzed. The growth rate, lag phase, and maximum optical density were obtained from each growth experiment, and after multivariate analysis, YNB-based media demonstrated a significant improvement in the growth of yeasts. Shaking, an inoculum size of 105 CFU/ml, and incubation at 30°C also improved the growth kinetics of organisms. Supplementation with ammonium sulfate and with 2% glucose did not have any effect on growth. We also tested the antifungal susceptibilities of all the isolates by the reference methods of the CLSI and EUCAST, the EUCAST method with shaking, YNB under static conditions, and YNB with shaking. MIC values obtained under different conditions showed high percentages of agreement and significant correlation coefficient values between them. MIC value determinations according to CLSI and EUCAST standards were rather complicated, since more than half of isolates tested showed a limited growth index, hampering endpoint determinations. We conclude that AST conditions including YNB as an assay medium, agitation of the plates, reading after 48 h of incubation, an inoculum size of 105 CFU/ml, and incubation at 30°C made MIC determinations easier without an overestimation of MIC values. PMID:21245438

  7. Population-Based Survey of Filamentous Fungi and Antifungal Resistance in Spain (FILPOP Study)

    PubMed Central

    Mellado, E.; Peláez, T.; Pemán, J.; Zapico, S.; Alvarez, M.; Rodríguez-Tudela, J. L.; Cuenca-Estrella, M.

    2013-01-01

    A population-based survey was conducted to investigate the epidemiology of and antifungal resistance in Spanish clinical strains of filamentous fungi isolated from deep tissue samples, blood cultures, and respiratory samples. The study was conducted in two different periods (October 2010 and May 2011) to analyze seasonal variations. A total of 325 strains were isolated in 29 different hospitals. The average prevalence was 0.0016/1,000 inhabitants. Strains were identified by sequencing of DNA targets and susceptibility testing by the European Committee for Antimicrobial Susceptibility Testing reference procedure. The most frequently isolated genus was Aspergillus, accounting for 86.3% of the isolates, followed by Scedosporium at 4.7%; the order Mucorales at 2.5%; Penicillium at 2.2%, and Fusarium at 1.2%. The most frequent species was Aspergillus fumigatus (48.5%), followed by A. flavus (8.4%), A. terreus (8.1%), A. tubingensis (6.8%), and A. niger (6.5%). Cryptic/sibling Aspergillus species accounted for 12% of the cases. Resistance to amphotericin B was found in 10.8% of the isolates tested, while extended-spectrum triazole resistance ranged from 10 to 12.7%, depending on the azole tested. Antifungal resistance was more common among emerging species such as those of Scedosporium and Mucorales and also among cryptic species of Aspergillus, with 40% of these isolates showing resistance to all of the antifungal compounds tested. Cryptic Aspergillus species seem to be underestimated, and their correct classification could be clinically relevant. The performance of antifungal susceptibility testing of the strains implicated in deep infections and multicentric studies is recommended to evaluate the incidence of these cryptic species in other geographic areas. PMID:23669377

  8. Population-based survey of filamentous fungi and antifungal resistance in Spain (FILPOP Study).

    PubMed

    Alastruey-Izquierdo, A; Mellado, E; Peláez, T; Pemán, J; Zapico, S; Alvarez, M; Rodríguez-Tudela, J L; Cuenca-Estrella, M

    2013-07-01

    A population-based survey was conducted to investigate the epidemiology of and antifungal resistance in Spanish clinical strains of filamentous fungi isolated from deep tissue samples, blood cultures, and respiratory samples. The study was conducted in two different periods (October 2010 and May 2011) to analyze seasonal variations. A total of 325 strains were isolated in 29 different hospitals. The average prevalence was 0.016/1,000 inhabitants [corrected]. Strains were identified by sequencing of DNA targets and susceptibility testing by the European Committee for Antimicrobial Susceptibility Testing reference procedure. The most frequently isolated genus was Aspergillus, accounting for 86.3% of the isolates, followed by Scedosporium at 4.7%; the order Mucorales at 2.5%; Penicillium at 2.2%, and Fusarium at 1.2%. The most frequent species was Aspergillus fumigatus (48.5%), followed by A. flavus (8.4%), A. terreus (8.1%), A. tubingensis (6.8%), and A. niger (6.5%). Cryptic/sibling Aspergillus species accounted for 12% of the cases. Resistance to amphotericin B was found in 10.8% of the isolates tested, while extended-spectrum triazole resistance ranged from 10 to 12.7%, depending on the azole tested. Antifungal resistance was more common among emerging species such as those of Scedosporium and Mucorales and also among cryptic species of Aspergillus, with 40% of these isolates showing resistance to all of the antifungal compounds tested. Cryptic Aspergillus species seem to be underestimated, and their correct classification could be clinically relevant. The performance of antifungal susceptibility testing of the strains implicated in deep infections and multicentric studies is recommended to evaluate the incidence of these cryptic species in other geographic areas. PMID:23669377

  9. Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity.

    PubMed

    Wróbel, Tomasz M; Kosikowska, Urszula; Kaczor, Agnieszka A; Andrzejczuk, Sylwia; Karczmarzyk, Zbigniew; Wysocki, Waldemar; Urba?czyk-Lipkowska, Zofia; Morawiak, Maja; Matosiuk, Dariusz

    2015-01-01

    Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed. PMID:26287137

  10. [Purification and characterization of a novel antifungal peptide APS-1 produced by Bacillus cereus].

    PubMed

    Pei, Y; Li, X; Peng, H; Chen, X; Liu, J

    1999-08-01

    In previous study, we isolated an antagonist Bacillus cereus strain: S-1 from cotton plant. In field experiments, this bacterium was shown strong inhibition to several plant diseases. In this paper, we reported the purification of the antifungal substance produced by the bacterium and its properties. After the steps of acid precipitation, methanol and ethy lether extraction, Sephadex G100 and DEAE52 column chromatography, the antifungal material was purified. The purified material had absorption peak at 275 nm, and was exhibited negative in biuret color reaction. However after hydrolyzed with HCl, this substance shown positive in the same reaction. Amino acid analysis to the hydrolysate of APS-1 showed that APS-1 was composed of Glu, Asp, Tyr, Ser, Thr, Pro, Leu, Ile, Val and an unknown amino acid. Combining with its pratial resistance to proteinases, it was suggested that this antifungal material was a cyclic peptide. This peptide, named APS-1, with strong inhibition on the germination of spores of the phytopathogens tested, was shown high stability against ultraviolet radiation and heat. APS-1 may have potential role in plant diseases biological control. PMID:12555574

  11. Ethnobotanical study, antifungal activity, phytochemical screening and total phenolic content of Algerian Aristolochia longa

    PubMed Central

    Benarba, Bachir; Meddah, Boumedienne

    2014-01-01

    Aim: Aristolochia longa (from the family Aristolochiaceae) is widely used in Algerian traditional medicine. Here, we document ethnomedicinal uses by local population of Mascara province (West Algeria) and we evaluate the antifungal activity, the phytochemical composition and total phenolic content of aqueous extract (decoction) of the roots of A. longa from Algeria. Materials and Methods: The ethnobotanical investigation was carried out in Mascara Province (West Algeria). Antifungal activity was assessed against Saccharomyces cerevisiae. Total phenolic content was measured using the Folin–Ciocalteu’s reagent. Results: Our results showed that A. longa is widely used to treat several ailments such as cancer (38%), skin infections (14%), and diabetes (11%). Crushed roots are commonly used (89%) mixed with honey, milk, water or other medicinal plants. A. longa aqueous extract induced growth inhibition of S. cerevisiae cells in a dose - and time - dependent manner. An effective suppression of S. cerevisiae (97.06% inhibition of proliferation) was obtained at the 500 µg/mL after 72 h. Results of the phytochemical screening revealed that A. longa aqueous extract contained various bioactive compounds, including polyphenols and flavonoids. Total phenolic content in A. longa aqueous extract was found to be 6.07 ± 0.12 mg (gallic acid equivalents)/g. Conclusion: A. longa may be considered as a promising source of new drugs for treating cancer and as a good antifungal agent. PMID:26401365

  12. In vitro antifungal activity of silver nanoparticles against fluconazole-resistant Candida species.

    PubMed

    Artunduaga Bonilla, Jhon J; Paredes Guerrero, Daissy J; Sánchez Suárez, Clara I; Ortiz López, Claudia C; Torres Sáez, Rodrigo G

    2015-11-01

    Nowadays, current advances in nanotechnology constitute a promising alternative in the development of new antimicrobial agents. Silver nanoparticles (AgNPs) are some very interesting products currently provided by available nanotechnology for control of microbial infection. In the present study, AgNPs were synthesized by eco-friendly method, using cysteine as a reducing agent. Also, antifungal activity against Candida species with resistance to fluconazole was evaluated through determination of Minimum Inhibitory Concentration (MIC50) according to protocol M27-A3 of Clinical and Laboratory Standards Institute (CLSI) and Minimum Fungicide Concentration (MFC). This study was carried out with strains Candida krusei and Candida glabrata. As a result, the formation of spherical nanoparticles was obtained with mean sizes of 19 nm and positive surface charge. Values of MIC50 were 0.1 µg ml(-1) AgNPs for the studied species, and MFC were 0.25 and 0.5 µg ml(-1) for C. glabrata and C. krusei, respectively. The AgNPs synthesized showed cytotoxic effect in 50% of Murine Fibroblast Cells (CC50) at a mean concentrations of 10 µg ml(-1) (100 times higher than MIC50). Consequently, AgNPs could be considered as an alternative potential in the development of new antifungal agents with minimum cytotoxicity in fibroblasts and lethal action on Candida species with resistance to conventional antifungal compounds. PMID:26335058

  13. Molecular identification and antifungal susceptibility of 186 Candida isolates from vulvovaginal candidiasis in southern China.

    PubMed

    Shi, Xiao-Yu; Yang, Yan-Ping; Zhang, Ying; Li, Wen; Wang, Jie-Di; Huang, Wen-Ming; Fan, Yi-Ming

    2015-04-01

    There is limited information regarding the molecular epidemiology and antifungal susceptibilities of Candida isolates using the Neo-Sensitabs method in patients with vulvovaginal candidiasis (VVC). From August 2012 to March 2013, 301 non-pregnant patients aged 18-50 years with suspected VVC were prospectively screened at a teaching hospital in southern China. The vaginal isolates were identified by DNA sequencing of internal transcribed spacer and the D1/D2 domain. Antifungal susceptibility testing of seven antifungal agents was performed using the Neo-Sensitabs tablet diffusion method. Candida species were isolated from 186 cases (61.79?%). The most common pathogen was Candida albicans (91.4?%), followed by Candida glabrata (4.3?%), Candida tropicalis (3.2?%) and Candida parapsilosis (1.1?%). The susceptibility rates to C. albicans were higher for caspofungin, voriconazole and fluconazole than those for itraconazole, miconazole, ketoconazole and terbinafine (P<0.01). The resistance rates to C. albicans were 4.7, 6.5, 7.1, 7.6, 12.3, 27.7 and 74.7?% for caspofungin, miconazole, itraconazole, voriconazole, fluconazole, ketoconazole and terbinafine, respectively. No drugs tested apart from fluconazole exhibited differences in resistance between C. albicans and non-albicans Candida isolates. The results demonstrate that, using DNA sequencing, C. albicans is the most common isolate from Chinese patients with VVC. Caspofungin, voriconazole and fluconazole may be preferable to other azoles and terbinafine in the treatment of VVC. PMID:25596116

  14. In vitro susceptibility patterns of clinically important Trichophyton and Epidermophyton species against nine antifungal drugs.

    PubMed

    Badali, Hamid; Mohammadi, Rasoul; Mashedi, Olga; de Hoog, G Sybren; Meis, Jacques F

    2015-05-01

    Despite the common, worldwide, occurrence of dermatophytes, little information is available regarding susceptibility profiles against currently available and novel antifungal agents. A collection of sixty-eight clinical Trichophyton species and Epidermophyton floccosum were previously identified and verified to the species level by sequencing the internal transcribed spacer (ITS) regions of rDNA. MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, terbinafine and MECs of caspofungin and anidulafungin were performed based on CLSI M38-A2. The resulting MIC90 s of all strains were, in increasing order, as follows: terbinafine (0.063 mg l(-1) ); posaconazole (1 mg l(-1) ); isavuconazole and anidulafungin (2 mg l(-1) ); itraconazole, voriconazole, amphotericin B, and caspofungin (4 mg l(-1) ) and fluconazole (>64 mg l(-1) ). These results confirm that terbinafine is an excellent agent for treatment of dermatophytosis due to T. rubrum, T. mentagrophytes, T. verrucosum, T. schoenleinii and E. floccosum. In addition, the new azoles POS and ISA are potentially useful antifungals to treat dermatophytosis. However, the clinical effectiveness of these novel antifungals remains to be determined. PMID:25757042

  15. Carbon and nitrogen limitation increase chitosan antifungal activity in Neurospora crassa and fungal human pathogens.

    PubMed

    Lopez-Moya, Federico; Colom-Valiente, Maria F; Martinez-Peinado, Pascual; Martinez-Lopez, Jesus E; Puelles, Eduardo; Sempere-Ortells, Jose M; Lopez-Llorca, Luis V

    2015-03-01

    Chitosan permeabilizes plasma membrane and kills sensitive filamentous fungi and yeast. Membrane fluidity and cell energy determine chitosan sensitivity in fungi. A five-fold reduction of both glucose (main carbon (C) source) and nitrogen (N) increased 2-fold Neurospora crassa sensitivity to chitosan. We linked this increase with production of intracellular reactive oxygen species (ROS) and plasma membrane permeabilization. Releasing N. crassa from nutrient limitation reduced chitosan antifungal activity in spite of high ROS intracellular levels. With lactate instead of glucose, C and N limitation increased N. crassa sensitivity to chitosan further (4-fold) than what glucose did. Nutrient limitation also increased sensitivity of filamentous fungi and yeast human pathogens to chitosan. For Fusarium proliferatum, lowering 100-fold C and N content in the growth medium, increased 16-fold chitosan sensitivity. Similar results were found for Candida spp. (including fluconazole resistant strains) and Cryptococcus spp. Severe C and N limitation increased chitosan antifungal activity for all pathogens tested. Chitosan at 100 ?g ml(-1) was lethal for most fungal human pathogens tested but non-toxic to HEK293 and COS7 mammalian cell lines. Besides, chitosan increased 90% survival of Galleria mellonella larvae infected with C. albicans. These results are of paramount for developing chitosan as antifungal. PMID:25749367

  16. A Critical Role for CLSP2 in the Modulation of Antifungal Immune Response in Mosquitoes

    PubMed Central

    Xing, Long-Sheng; Jiang, Hong; Hu, Song-Nian; Raikhel, Alexander S.; Zou, Zhen

    2015-01-01

    Entomopathogenic fungi represent a promising class of bio-insecticides for mosquito control. Thus, detailed knowledge of the molecular mechanisms governing anti-fungal immune response in mosquitoes is essential. In this study, we show that CLSP2 is a modulator of immune responses during anti-fungal infection in the mosquito Aedes aegypti. With a fungal infection, the expression of the CLSP2 gene is elevated. CLSP2 is cleaved upon challenge with Beauveria bassiana conidia, and the liberated CLSP2 CTL-type domain binds to fungal cell components and B. bassiana conidia. Furthermore, CLPS2 RNA interference silencing significantly increases the resistance to the fungal challenge. RNA-sequencing transcriptome analysis showed that the majority of immune genes were highly upregulated in the CLSP2-depleted mosquitoes infected with the fungus. The up-regulated immune gene cohorts belong to melanization and Toll pathways, but not to the IMD or JAK-STAT. A thioester-containing protein (TEP22), a member of ?2-macroglobulin family, has been implicated in the CLSP2-modulated mosquito antifungal defense. Our study has contributed to a greater understanding of immune-modulating mechanisms in mosquitoes. PMID:26057557

  17. A Critical Role for CLSP2 in the Modulation of Antifungal Immune Response in Mosquitoes.

    PubMed

    Wang, Yan-Hong; Hu, Yang; Xing, Long-Sheng; Jiang, Hong; Hu, Song-Nian; Raikhel, Alexander S; Zou, Zhen

    2015-06-01

    Entomopathogenic fungi represent a promising class of bio-insecticides for mosquito control. Thus, detailed knowledge of the molecular mechanisms governing anti-fungal immune response in mosquitoes is essential. In this study, we show that CLSP2 is a modulator of immune responses during anti-fungal infection in the mosquito Aedes aegypti. With a fungal infection, the expression of the CLSP2 gene is elevated. CLSP2 is cleaved upon challenge with Beauveria bassiana conidia, and the liberated CLSP2 CTL-type domain binds to fungal cell components and B. bassiana conidia. Furthermore, CLPS2 RNA interference silencing significantly increases the resistance to the fungal challenge. RNA-sequencing transcriptome analysis showed that the majority of immune genes were highly upregulated in the CLSP2-depleted mosquitoes infected with the fungus. The up-regulated immune gene cohorts belong to melanization and Toll pathways, but not to the IMD or JAK-STAT. A thioester-containing protein (TEP22), a member of ?2-macroglobulin family, has been implicated in the CLSP2-modulated mosquito antifungal defense. Our study has contributed to a greater understanding of immune-modulating mechanisms in mosquitoes. PMID:26057557

  18. Antifungal activity of diketopiperazines and stilbenes against plant pathogenic fungi in vitro.

    PubMed

    Kumar, S Nishanth; Nambisan, Bala

    2014-01-01

    The present study aimed to investigate antifungal activity of a stilbene and diketopiperazine compounds against plant pathogenic fungi, including Phytophthora capsici, P. colocasiae, Botrytis cinerea and Colletotrichum gloeosporioides. Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) of stilbenes and diketopiperazines for each fungus were determined using microplate method. Best activity was recorded by stilbenes against P. capsici and P. colocasiae. All four test compounds were effective in inhibiting different stages of the life cycle of test fungi. Stilbenes were more effective than diketopiperazines in inhibiting mycelial growth and inhibiting different stages of the life cycle of P. capsici and P. colocasiae. Rupture of released zoospores induced by stilbenes was reduced by addition of 100 mM glucose. The effects of stilbenes on mycelial growth and zoospore release, but not zoospore rupture, were reduced largely when pH value was above 7. In addition, stilbenes were investigated for its antifungal stability against Phytophthora sp. The results showed that stilbenes maintained strong fungistatic activity over a wide pH range (pH 4–9) and temperature range (70–120 °C). The compound stilbenes exhibited strong and stable broad-spectrum antifungal activity, and had a significant fungicidal effect on fungal cells. Results from prebiocontrol evaluations performed to date are probably useful in the search for alternative approaches to controlling serious plant pathogens. PMID:24122628

  19. Identification of antifungal niphimycin from Streptomyces sp. KP6107 by screening based on adenylate kinase assay.

    PubMed

    Kim, Hye Yoon; Kim, Jeong Do; Hong, Jin Sung; Ham, Jong Hyun; Kim, Beom Seok

    2013-07-01

    Microbial culture extracts are used for natural product screening to find antifungal lead compounds. A microbial culture extract library was constructed using 343 actinomycete isolates to examine the value of the adenylate kinase (AK) assay for screening to identify antifungal metabolites that disrupt cell integrity in plant pathogenic fungi. A culture extract of Streptomyces sp. strain KP6107 lysed cells of Fusarium oxysporum f.sp. lycopersici which resulted in high AK activity. The active ingredient N-1 was purified from the culture extract using various chromatographic procedures and identified to be the guanidyl-polyol macrolide antibiotic, niphimycin, which is a potent fungal cell membrane disruptor. Niphimycin showed broad-spectrum antifungal activity against Alternaria mali, Aspergillus oryzae, Colletotrichum coccodes, Colletotrichum gloeosporioides, Cercospora canescens, Cylindrocarpon destructans, F. oxysporum f.sp. cucumerinum, F. oxysporum f.sp. lycopersici, and Rhizoctonia solani at concentrations of 8-64?µg?ml(-1). Anthracnose development in pepper plants was completely inhibited by treatment with 50 µg?ml(-1) niphimycin, which was as effective as chlorothalonil. These results show that the AK assay is an efficient and selective tool in screening for cell membrane/wall disruptors of plant pathogenic fungi. PMID:22915202

  20. Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana

    PubMed Central

    Eilenberg, Haviva; Pnini-Cohen, Smadar; Rahamim, Yocheved; Sionov, Edward; Segal, Esther; Carmeli, Shmuel; Zilberstein, Aviah

    2010-01-01

    Nepenthes spp. are carnivorous plants that have developed insect capturing traps, evolved by specific modification of the leaf tips, and are able to utilize insect degradation products as nutritional precursors. A chitin-induced antifungal ability, based on the production and secretion to the trap liquid of droserone and 5-O-methyldroserone, is described here. Such specific secretion uniquely occurred when chitin injection was used as the eliciting agent and probably reflects a certain kind of defence mechanism that has been evolved for protecting the carnivory-based provision of nutritional precursors. The pitcher liquid containing droserone and 5-O-methyldroserone at 3:1 or 4:1 molar ratio, as well as the purified naphthoquinones, exerted an antifungal effect on a wide range of plant and human fungal pathogens. When tested against Candida and Aspergillus spp., the concentrations required for achieving inhibitory and fungicidal effects were significantly lower than those causing cytotoxicity in cells of the human embryonic kidney cell line, 293T. These naturally secreted 1,4-naphthoquinone derivatives, that are assumed to act via semiquinone enhancement of free radical production, may offer a new lead to develop alternative antifungal drugs with reduced selectable pressure for potentially evolved resistance. PMID:20018905

  1. Antifungal Drug Discovery & Development - Fifth International Summit. 28-29 March 2001, Princeton, NJ, USA.

    PubMed

    Everett, N

    2001-06-01

    Reviews of recent clinical trials of marketed and investigational antifungal products revealed a number of recurring themes. There is currently a severely limited arsenal of antifungal drugs from which clinicians can choose. Many of the new products are improved versions or formulations of existing chemistries and modes of action, all of which still have some serious limitations, such as toxicity, insufficient solubility, rapid evolution of drug resistance, cost, and antagonisms when used in combination with other drug therapies. Specific sequential treatments with existing drugs appear to offer some promise, but problems in recruiting sufficient 'clean patients', who do not have many other health problems and complicated treatment histories, confounds such trials. Also, the current registration process requires the demonstration of efficacy as a single agent. Recent advances in the identification and validation of new drug targets, screening technologies and efficient exploitation of new chemistries from natural products appears to offer significant promise for the future. It will be of interest to see how quickly these advances in drug discovery result in new and improved antifungal drugs in commercial development pipelines. PMID:16001308

  2. Antifungal activity of the essential oil of Angelica major against Candida, Cryptococcus, Aspergillus and dermatophyte species.

    PubMed

    Cavaleiro, Carlos; Salgueiro, Lígia; Gonçalves, Maria-José; Hrimpeng, Karnjana; Pinto, Jéssica; Pinto, Eugénia

    2015-04-01

    The composition and antifungal activity of the essential oil (EO) of Angelica major and its main components ?-pinene and cis-?-ocimene against clinically relevant yeasts and moulds were evaluated. EO from the plant's aerial parts was obtained by hydrodistillation and analysed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The oil showed high contents of ?-pinene (21.8 %) and cis-?-ocimene (30.4 %). Minimum inhibitory concentrations (MICs) were measured according to the broth macrodilution protocols by the Clinical and Laboratory Standards Institute (CLSI). The EO, ?-pinene and cis-?-ocimene displayed low MICs and minimum fungicidal concentrations (MFCs) against dermatophytes and Cryptococcus neoformans, with ?-pinene being the most active. Regarding Candida species, the EO susceptibility profiles seem to be diverse and not correlated with fluconazole susceptibility patterns. Moreover, an inhibition of yeast-mycelium transition was demonstrated at sub-inhibitory concentrations of the EO, ?-pinene and cis-?-ocimene in C. albicans. In addition, their haemolytic activity was low. The activity displayed by A. major EO and its main components associated with low cytotoxic activity confirms their potential as an antifungal agent against fungal species frequently implicated in human mycoses, particularly cryptococcosis and dermatophytosis. The association with commercial antifungal compounds could bring benefits, by the effect on germ tube formation, and be used in mucocutaneous candidiasis treatment. PMID:25576097

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

    PubMed Central

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

    2012-01-01

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

  4. Isolation and characterization of an antifungal protein from Bacillus licheniformis HS10.

    PubMed

    Wang, Zhixin; Wang, Yunpeng; Zheng, Li; Yang, Xiaona; Liu, Hongxia; Guo, Jianhua

    2014-11-01

    Bacillus licheniformis HS10 is a good biocontrol agent against Pseudoperonospora cubensis which caused cucumber downy disease. To identify and characterize the antifungal proteins produced by B.licheniformis HS10, the proteins from HS10 were isolated by using 30-60% ammonium sulfate precipitation, and purified with column chromatography on DEAE Sepharose Fast Flow, RESOURCE Q and Sephadex G-75. And the SDS-PAGE and MALDI-TOF/TOF-MS analysis results demonstrated that the antifungal protein was a monomer with molecular weight of about 55 kDa, identified as carboxypeptidase. Our experiments also showed that the antifungal protein from B. licheniformis HS10 had significantly inhibition on eight different kinds of plant pathogenic fungi, and it was stable with good biological activity at as high as 100°C for 30 min and in pH value ranged from 6 to 10. The biological activity was negatively affected by protease K and 10mM metal cations except Ca(2+). PMID:25445597

  5. Assessment of Antifungal Activity of Bakuchiol on Oral-Associated Candida spp.

    PubMed Central

    Nordin, Mohd-Al-Faisal; Abdul Razak, Fathilah; Himratul-Aznita, Wan Harun

    2015-01-01

    Bakuchiol is an active component of Psoralea glandulosa and Psoralea corylifolia, used in traditional Chinese medicine. The study aimed at investigating the antifungal activity of bakuchiol on planktonic and biofilm forms of orally associated Candida species. The antifungal susceptibility testing was determined by the broth micro dilution technique. Growth kinetics and cell surface hydrophobicity (CSH) of Candida were measured to assess the inhibitory effect of bakuchiol on Candida planktonic cells. Biofilm biomass and cellular metabolic activity were quantitatively estimated by the crystal violet (CV) and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assays. All Candida strains have been shown to be susceptible to bakuchiol with the MIC ranges from 12.5 to 100??g/mL. Significant decrease in specific growth rates and viable counts demonstrates the inhibitory effect of bakuchiol on Candida planktonic cells. A brief exposure to bakuchiol also reduced CSH of Candida (P < 0.05), indicating altered surface properties of yeast cells towards hydrophobic interfaces. Biofilm biomass and cell metabolic activity were mostly decreased, except for C. glabrata (P = 0.29). The antifungal properties of bakuchiol on Candida species in this in vitro study may give insights into the application in therapeutic strategy against Candida infections. PMID:26633986

  6. Antifungal Activity of 14-Helical ?-Peptides against Planktonic Cells and Biofilms of Candida Species

    PubMed Central

    Raman, Namrata; Lee, Myung-Ryul; Lynn, David M.; Palecek, Sean P.

    2015-01-01

    Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical ?-peptide structural mimetics of natural antimicrobial ?-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that ?-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to ?-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. ?-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While ?-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic ?-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of ?-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics. PMID:26287212

  7. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens.

    PubMed

    Radwan, Mohamed M; Tabanca, Nurhayat; Wedge, David E; Tarawneh, Amer H; Cutler, Stephen J

    2014-12-01

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. Among the active extracts, turmeric and nutmeg were the most active and were chosen for further investigation. The bioassay-guided fractionation led to the isolation of three compounds from turmeric (1-3) and three compounds from nutmeg (4-6). Their chemical structures were elucidated by spectroscopic analysis including HR-MS, 1D, and 2D NMR as curcumin (1), demethoxycurcumin (2) and bisdemethoxy-curcumin (3), erythro-(7R,8R)-?(8')-4,7-dihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (4), erythro-(7R,8R)-?8'-7-acetoxy-3,4,3',5'-tetra-methoxy-8-O-4'-neolignan (5), and 5-hydroxy-eugenol (6). The isolated compounds were subsequently evaluated using a 96-well microbioassay against plant pathogens. At 30 ?M, compounds 2 and 3 possessed the most antifungal activity against Phomopsis obscurans and Phomopsis viticola, respectively. PMID:25173461

  8. Metal-based carboxamide-derived compounds endowed with antibacterial and antifungal activity.

    PubMed

    Hanif, Muhammad; Chohan, Zahid H; Winum, Jean-Yves; Akhtar, Javeed

    2014-08-01

    A series of three bioactive thiourea (carboxamide) derivatives, N-(dipropylcarbamothioyl)-thiophene-2-carboxamide (L(1)), N-(dipropylcarbamothioyl)-5-methylthiophene-2-carboxamide (L(2)) and 5-bromo-N-(dipropylcarbamothioyl)furan-2-carboxamide (L(3)) and their cobalt(II), copper(II), nickel(II) and zinc(II) complexes (1)-(12) have been synthesized and characterized by their IR,(1)H-NMR spectroscopy, mass spectrometry and elemental analysis data. The Crystal structure of one of the ligand, N-(dipropylcarbamothioyl)thiophene-2-carboxamide (L(1)) and its nickel(II) and copper(II) complexes were determined from single crystal X-ray diffraction data. All the ligands and metal(II) complexes have been subjected to in vitro antibacterial and antifungal activity against six bacterial species (Escherichia coli. Shigella flexneri. Pseudomonas aeruginosa. Salmonella typhi. Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal strains (Trichophyton longifusus. Candida albicans. Aspergillus flavus. Microsporum canis. Fusarium solani and Candida glabrata). The in vitro antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent than the parent ligands against one or more bacterial and fungal strains. PMID:23914928

  9. An ancient plant Lawsonia inermis (henna): determination of in vitro antifungal activity against dermatophytes species.

    PubMed

    Gozubuyuk, G S; Aktas, E; Yigit, N

    2014-12-01

    World is endowed with a rich wealth of medicinal plants. There is a widespread belief that green medicines are healthier and more harmless or safer than synthetic ones. Medicinal plants have been used to cure a number of diseases. The ancient plant Lawsonia inermis or henna is used as medicinal plant because of its attributed strong fungicidal, anti-inflammatory, analgesic, antibacterial, virucidal, antiparasitic, antiamoebiasis, astringent, antihemorrhagic, hypotensive, sedative, anticancer effect and possible anti-sweating properties. In this study, we investigated antifungal activity of L. inermis against clinical dermatophytes species. This study was carried out using 70 clinical isolates of dermatophytes representing six different species; 44 Trichophyton rubrum, 8 Trichophyton mentagrophytes, 6 Microsporum canis, 6 Trichophyton tonsurans, 4 Epidermophyton floccosum, and 2 Trichophyton violaceum. The antifungal activity of L. inermis (henna) was determined by agar diffusion method and henna was used as paste form. Henna paste showed the high antifungal activity against all dermatophytes species (20 to 50mm inhibition zone). PMID:25442917

  10. Plant-derived antifungal agent poacic acid targets ?-1,3-glucan.

    PubMed

    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

    2015-03-24

    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 ?-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding ?-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 ?-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

  11. Antifungal activity of plant extracts against Arthrinium sacchari and Chaetomium funicola.

    PubMed

    Sato, J; Goto, K; Nanjo, F; Kawai, S; Murata, K

    2000-01-01

    Various plant extracts were examined for antifungal activity with the objective of improving the commercial sterility of aseptically filled tea beverage products in PET bottles. When the hot water extract and the methanol extract of 29 samples were measured for their antifungal activity against Arthrinium sacchari M001 and Chaetomium funicola M002 strains, five samples, Acer nikoense, Glycyrrhiza glabra, Lagerstroemia speciosa, Psidium guajava and Thea sinensis, showed high activity. Of these, the extracts from A. nikoense, G. glabra and T. sinensis were fractionated by extraction with CHCl3, and the CHCl3-soluble fractions from G. glabra showed antifungal activity with minimum inhibitory concentrations (MICs) between 62.5 and 125 microg/ml against the above-mentioned two fungi. When the EtOAc-soluble fraction of A. nikoense was used, the MIC against A. sacchari M001 was 62.5 microg/ml. However, none of the fractions from A. nikoense or T. sinensis showed high activity against C. funicola M002 and their MICs were greater than 500 microg/ml. A licorice preparation made from the commercially available oil-based extract of G. glabra showed a low MIC of 25 microg/ml against five tested strains of filamentous fungi, but not against Aspergillus fumigatus M008, in a blended tea. Consequently, the possibility of adding a licorice preparation made from the oil-based extract of G. glabra to tea beverages (aseptically filled into PET bottles) was suggested. PMID:16232887

  12. In Vitro Antifungal Activity of Burkholderia gladioli pv. agaricicola against Some Phytopathogenic Fungi

    PubMed Central

    Elshafie, Hazem S.; Camele, Ippolito; Racioppi, Rocco; Scrano, Laura; Iacobellis, Nicola S.; Bufo, Sabino A.

    2012-01-01

    The trend to search novel microbial natural biocides has recently been increasing in order to avoid the environmental pollution from use of synthetic pesticides. Among these novel natural biocides are the bioactive secondary metabolites of Burkholderia gladioli pv. agaricicola (Bga). The aim of this study is to determine antifungal activity of Bga strains against some phytopathogenic fungi. The fungicidal tests were carried out using cultures and cell-free culture filtrates against Botrytis cinerea, Aspergillus flavus, Aspergillus niger, Penicillium digitatum, Penicillium expansum, Sclerotinia sclerotiorum and Phytophthora cactorum. Results demonstrated that all tested strains exert antifungal activity against all studied fungi by producing diffusible metabolites which are correlated with their ability to produce extracellular hydrolytic enzymes. All strains significantly reduced the growth of studied fungi and the bacterial cells were more bioactive than bacterial filtrates. All tested Bulkholderia strains produced volatile organic compounds (VOCs), which inhibited the fungal growth and reduced the growth rate of Fusarium oxysporum and Rhizoctonia solani. GC/MS analysis of VOCs emitted by strain Bga 11096 indicated the presence of a compound that was identified as 1-methyl-4-(1-methylethenyl)-cyclohexene, a liquid hydrocarbon classified as cyclic terpene. This compound could be responsible for the antifungal activity, which is also in agreement with the work of other authors. PMID:23208371

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

    PubMed Central

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

    2014-01-01

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

  14. Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin

    SciTech Connect

    Neuhof, Torsten . E-mail: t.neuhof@gmx.de; Seibold, Michael; Thewes, Sascha; Laue, Michael; Han, Chang-Ok; Hube, Bernhard; Doehren, Hans von

    2006-10-20

    This is First report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 {mu}g/ml, independently from the species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different.

  15. An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products.

    PubMed

    Mousa, Walaa K; Schwan, Adrian; Davidson, Jeffrey; Strange, Philip; Liu, Huaizhi; Zhou, Ting; Auzanneau, France-Isabelle; Raizada, Manish N

    2015-01-01

    Finger millet is an ancient African cereal crop, domesticated 7000 years ago in Ethiopia, reaching India at 3000 BC. Finger millet is reported to be resistant to various fungal pathogens including Fusarium sp. We hypothesized that finger millet may host beneficial endophytes (plant-colonizing microbes) that contribute to the antifungal activity. Here we report the first isolation of endophyte(s) from finger millet. Five distinct fungal species were isolated from roots and predicted taxonomically based on 18S rDNA sequencing. Extracts from three putative endophytes inhibited growth of F. graminearum and three other pathogenic Fusarium species. The most potent anti-Fusarium strain (WF4, predicted to be a Phoma sp.) was confirmed to behave as an endophyte using pathogenicity and confocal microscopy experiments. Bioassay-guided fractionation of the WF4 extract identified four anti-fungal compounds, viridicatol, tenuazonic acid, alternariol, and alternariol monomethyl ether. All the purified compounds caused dramatic breakage of F. graminearum hyphae in vitro. These compounds have not previously been reported to have anti-Fusarium activity. None of the compounds, except for tenuazonic acid, have previously been reported to be produced by Phoma. We conclude that the ancient, disease-tolerant crop, finger millet, is a novel source of endophytic anti-fungal natural products. This paper suggests the value of the crops grown by subsistence farmers as sources of endophytes and their natural products. Application of these natural chemicals to solve real world problems will require further validation. PMID:26539183

  16. Comparison of Antifungal Activity of 2% Chlorhexidine, Calcium Hydroxide, and Nanosilver gels against Candida Albicans

    PubMed Central

    Mozayeni, Mohammad Ali; Hadian, Ali; Bakhshaei, Pedram; Dianat, Omid

    2015-01-01

    Objectives: Residual microorganisms in the root canal system (RCS) after endodontic therapy such as Candida albicans are a major cause of endodontic failure. Calcium hydroxide (CH) and chlorhexidine (CHX) have suitable antimicrobial activity against bacteria and can be used as intracanal medicaments. Nanosilver has also shown antimicrobial activity against microorganisms. This study aimed to compare the antifungal effect of calcium hydroxide, 2% chlorhexidine and nanosilver gels on Candida albicans. Materials and Methods: Eighty-one single-rooted teeth were selected. After root canal preparation, the teeth were contaminated. After culture, the teeth were randomly divided into 4 groups. In experimental groups, 24 teeth were selected and completely filled with CH, 2% CHX and nanosilver gels in each group. Nine teeth were selected in the control group and filled with saline solution. After 1, 3, and 7 days, samples were obtained by #30 sterile paper points, and #2 and #4 Gates Glidden drills and cultured on solid Sabouraud agar. Results: The results demonstrated that CH and 2% CHX had equal antifungal effects on samples taken by paper point and #2 Gates Glidden drill at all time points. Both CH and 2% CHX were more effective than nanosilver at all time periods. There was no statistically significant difference between medicaments in samples taken by #4 Gates Glidden drill. Conclusion: CH and 2% CHX gels have significantly higher antifungal activity than nanosilver gel. Also, CH and 2% CHX gels are equally effective against Candida albicans. PMID:26056520

  17. A new Co(II) complex of diniconazole: synthesis, crystal structure and antifungal activity.

    PubMed

    Xi, Teng; Li, Jie; Yan, Biao; Yang, Mingyan; Song, Jirong; Ma, Haixia

    2015-10-01

    A new Co(II) complex of diniconazole, namely diaqua[(E)-(RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-?N(4))pent-1-en-3-ol]cobalt(II) dinitrate dihydrate, [Co(C15H17Cl2N3O)3(H2O)2](NO3)2·2H2O, was synthesized and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Crystal structural analysis shows that the centrosymmetric Co(II) cation is coordinated by four diniconazole ligands and two water molecules, forming a six-coordinated octahedral structure. There are also two free nitrate counter-anions and two additional solvent water molecules in the structure. Intermolecular O-H...O hydrogen bonds link the complex cations into a one-dimensional chain. In addition, the antifungal activity of the complex against Botryosphaeria ribis, Gibberella nicotiancola, Botryosphaeria berengriana and Alternariasolani was studied. The results indicate that the complex shows a higher antifungal activity for Botryosphaeria ribis and Botryosphaeria berengriana than diniconazole, but a lower antifungal activity for Gibberella nicotiancola and Alternariasolani. PMID:26422217

  18. A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

    PubMed Central

    Xue, Jingzhe; Luo, Zhihui; Li, Ping; Ding, Yaping; Cui, Yi; Wu, Qingsheng

    2014-01-01

    Here we reported a residue-free green nanotechnology which synergistically enhance the pesticides efficiency and successively eliminate its residue. We built up a composite antifungal system by a simple pre-treating and assembling procedure for investigating synergy. Investigations showed 0.25?g/L ZnO nanoparticles (NPs) with 0.01?g/L thiram could inhibit the fungal growth in a synergistic mode. More importantly, the 0.25?g/L ZnO NPs completely degraded 0.01?g/L thiram under simulated sunlight irradiation within 6?hours. It was demonstrated that the formation of ZnO-thiram antifungal system, electrostatic adsorption of ZnO NPs to fungi cells and the cellular internalization of ZnO-thiram composites played important roles in synergy. Oxidative stress test indicated ZnO-induced oxidative damage was enhanced by thiram that finally result in synergistic antifungal effect. By reducing the pesticides usage, this nanotechnology could control the plant disease economically, more significantly, the following photocatalytic degradation of pesticide greatly benefit the human social by avoiding negative influence of pesticide residue on public health and environment. PMID:25023938

  19. Plant-derived antifungal agent poacic acid targets ?-1,3-glucan

    PubMed Central

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

    2015-01-01

    A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited ?-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding ?-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 ?-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

  20. Trafficking through the late endosome significantly impacts Candida albicans tolerance of the azole antifungals.

    PubMed

    Luna-Tapia, Arturo; Kerns, Morgan E; Eberle, Karen E; Jursic, Branko S; Palmer, Glen E

    2015-04-01

    The azole antifungals block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of "toxic" sterol intermediates are both thought to compromise plasma membrane function. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, a C. albicans vps21?/? mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. Furthermore, the vps21?/? mutant is able to grow despite the depletion of cellular ergosterol. This phenotype resembles an exaggerated form of "trailing growth" that has been described for some clinical isolates. In contrast, the vps21?/? mutant is hypersensitive to drugs that block alternate steps in ergosterol biosynthesis. On the basis of these results, we propose that endosomal trafficking defects may lead to the cellular "redistribution" of the sterol intermediates that accumulate following inhibition of ergosterol biosynthesis. Furthermore, the destination of these intermediates, or the precise cellular compartments in which they accumulate, may be an important determinant of their toxicity and thus ultimately antifungal efficacy. PMID:25666149

  1. Trafficking through the Late Endosome Significantly Impacts Candida albicans Tolerance of the Azole Antifungals

    PubMed Central

    Luna-Tapia, Arturo; Kerns, Morgan E.; Eberle, Karen E.; Jursic, Branko S.

    2015-01-01

    The azole antifungals block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of “toxic” sterol intermediates are both thought to compromise plasma membrane function. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, a C. albicans vps21?/? mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. Furthermore, the vps21?/? mutant is able to grow despite the depletion of cellular ergosterol. This phenotype resembles an exaggerated form of “trailing growth” that has been described for some clinical isolates. In contrast, the vps21?/? mutant is hypersensitive to drugs that block alternate steps in ergosterol biosynthesis. On the basis of these results, we propose that endosomal trafficking defects may lead to the cellular “redistribution” of the sterol intermediates that accumulate following inhibition of ergosterol biosynthesis. Furthermore, the destination of these intermediates, or the precise cellular compartments in which they accumulate, may be an important determinant of their toxicity and thus ultimately antifungal efficacy. PMID:25666149

  2. Extracellular DNA Release Acts as an Antifungal Resistance Mechanism in Mature Aspergillus fumigatus Biofilms

    PubMed Central

    Rajendran, Ranjith; Williams, Craig; Lappin, David F.; Millington, Owain; Martins, Margarida

    2013-01-01

    Aspergillus fumigatus has been shown to form biofilms that are associated with adaptive antifungal resistance mechanisms. These include multidrug efflux pumps, heat shock proteins, and extracellular matrix (ECM). ECM is a key structural and protective component of microbial biofilms and in bacteria has been shown to contain extracellular DNA (eDNA). We therefore hypothesized that A. fumigatus biofilms also possess eDNA as part of the ECM, conferring a functional role. Fluorescence microscopy and quantitative PCR analyses demonstrated the presence of eDNA, which was released phase dependently (8 < 12 < 24 < 48 h). Random amplification of polymorphic DNA (RAPD) PCR showed that eDNA was identical to genomic DNA. Biofilm architectural integrity was destabilized by DNase treatment. Biochemical and transcriptional analyses showed that chitinase activity and mRNA levels of chitinase, a marker of autolysis, were significantly upregulated as the biofilm matured and that inhibition of chitinases affected biofilm growth and stability, indicating mechanistically that autolysis was possibly involved. Finally, using checkerboard assays, it was shown that combinational treatment of biofilms with DNase plus amphotericin B and caspofungin significantly improved antifungal susceptibility. Collectively, these data show that eDNA is an important structural component of A. fumigatus ECM that is released through autolysis, which is important for protection from environmental stresses, including antifungal therapy. PMID:23314962

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

    PubMed Central

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

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N?-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N?-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  4. Substrate dependent in vitro antifungal activity of Bacillus sp strain AR2

    PubMed Central

    2014-01-01

    Background Biosurfactants are a structurally diverse group of secondary metabolites with lots of potential to serve mankind. Depending upon the structure and composition they may exhibit properties that make them suitable for a particular application. Structural and compositional diversity of biosurfactant is unambiguously substrate dependent. The present study investigates the qualitative and quantitative effect of different water soluble carbon source on the biosurfactant produced by Bacillus amylofaciens strain AR2. Results Strain AR2 produced lipopeptide type biosurfactant while growing on water soluble carbon sources. Maximum biosurfactant production was observed in the sucrose supplemented minimal salt medium (MSM). Strain AR2 exhibited carbon source dependent surface tension reduction in the range of 30-37 mN/m, critical micelle concentration (CMC) in the range 80-110 mg/l and emulsification index (EI24 kerosene) in the range of 32-66%. In dextrose, sucrose and glycerol supplemented MSM, strain AR2 produced lipopeptides as a mixture of surfactin, iturin and fengycin. However, in the presence of maltose, lactose and sorbitol only iturin was produced. This substrate dependent compositional variation in the lipopeptides significantly influenced antifungal activity. Lipopeptides produced by strain AR2 while growing on sucrose and dextrose based MSM was observed to be most efficient as an antifungal agent. Conclusions These results suggest that carbon source provided for the growth and biosurfactant production not only influences the yield but also the type of biosurfactant. Sucrose is the most suitable carbon source for production of lipopeptide biosurfactant with antifungal activity. PMID:24885467

  5. Reliability of the WIDERYST Susceptibility Testing System for Detection of In Vitro Antifungal Resistance in Yeasts?

    PubMed Central

    Cuenca-Estrella, Manuel; Gomez-Lopez, Alicia; Gutierrez, M. Olga; Buitrago, M. Jose; Rodriguez-Tudela, Juan L.

    2008-01-01

    This study evaluated the WIDERYST system, a commercially available computer-assisted image-processing device for the antifungal susceptibility testing of yeasts. A collection of 90 clinical isolates selected to represent ranges of susceptibilities in vitro as broad as possible was tested. An evaluation compared the results obtained by the new system with those achieved by both the Clinical and Laboratory Standards Institute (CLSI) microdilution reference procedure and the antifungal susceptibility standard of the European Committee for Antimicrobial Susceptibility Testing (EUCAST). Overall, the agreement and the correlation index between results obtained by the EUCAST method and the WIDERYST system were 89% and 0.84 (P < 0.01), respectively, and agreement and correlation index between data obtained by the CLSI procedure and the WIDERYST system were 90% and 0.86 (P < 0.01), respectively. The system was able to detect amphotericin B-resistant isolates. All Candida sp. isolates with resistance in vitro to azole agents were detected as well. The system misclassified some isolates belonging to the slowly growing genera Dipodascus and Pichia. A total of 2.7% very major errors were detected for fluconazole. The WIDERYST system is an alternative to reference procedures for antifungal susceptibility testing of clinical isolates of yeasts, particularly for Candida and Cryptococcus species. PMID:18195057

  6. Antifungal and antibacterial activity of the essential oil of Chamaecyparis lawsoniana from Spain.

    PubMed

    Palá-Paúl, Jesús; Usano-Alemany, Jaime; Granda, Elena; Soria, Ana-Cristina

    2012-10-01

    The essential oils extracted from the young stems and leaves of Chamaecyparis lawsoniana (A.Murray) Parl. have been analysed by Gas Chromatography and Gas Chromatography coupled to Mass Spectrometry. A total of 66 compounds were identified representing around the 99% of the total oil. The oil was richer in monoterpenes than in sesquiterpenes. The only main component was limonene with a percentage composition of 77.7%. The rest of compounds that contribute to the fragrance had percentage composition lower that the 3.0%: p-cymen-7-ol (3.0%), myrcene (2.4%), camphor (2.1%), delta-elemene (1.6%), oplopanonyl acetate (1.6%), methyl perillate (1.3%), terpinen-4-ol (1.0%) and beta-oplopenone 1.0%. The antibacterial and antifungal activity of this oil was also tested against different microorganisms. The only fungus tested, Candida albicans, was very sensitive to the treatment with an inhibition halos of 20mm. The oil was more effective with the Gram (+) than with Gram (-) bacteria. The inhibition halos were 12mm, 12-13mm and 12-13mm for Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus respectively. We report new data of the antibacterial and antifungal activity of the essential oil of this species. The essential oil of C. lawsoniana could be considered as a good natural antibacterial and antifungal agent. PMID:23157017

  7. Identification of New Antifungal Compounds Targeting Thioredoxin Reductase of Paracoccidioides Genus

    PubMed Central

    Abadio, Ana Karina Rodrigues; Kioshima, Erika Seki; Leroux, Vincent; Martins, Natalia Floręncio; Maigret, Bernard; Felipe, Maria Sueli Soares

    2015-01-01

    The prevalence of invasive fungal infections worldwide has increased in the last decades. The development of specific drugs targeting pathogenic fungi without producing collateral damage to mammalian cells is a daunting pharmacological challenge. Indeed, many of the toxicities and drug interactions observed with contemporary antifungal therapies can be attributed to “nonselective” interactions with enzymes or cell membrane systems found in mammalian host cells. A computer-aided screening strategy against the TRR1 protein of Paracoccidioides lutzii is presented here. Initially, a bank of commercially available compounds from Life Chemicals provider was docked to model by virtual screening simulations. The small molecules that interact with the model were ranked and, among the best hits, twelve compounds out of 3,000 commercially-available candidates were selected. These molecules were synthesized for validation and in vitro antifungal activity assays for Paracoccidioides lutzii and P. brasiliensis were performed. From 12 molecules tested, 3 harbor inhibitory activity in antifungal assays against the two pathogenic fungi. Corroborating these findings, the molecules have inhibitory activity against the purified recombinant enzyme TRR1 in biochemical assays. Therefore, a rational combination of molecular modeling simulations and virtual screening of new drugs has provided a cost-effective solution to an early-stage medicinal challenge. These results provide a promising technique to the development of new and innovative drugs. PMID:26569405

  8. Endophytic bacterial communities in ginseng and their antifungal activity against pathogens.

    PubMed

    Cho, Kye Man; Hong, Su Young; Lee, Sun Mi; Kim, Yong Hee; Kahng, Goon Gjung; Lim, Yong Pyo; Kim, Hoon; Yun, Han Dae

    2007-08-01

    Plant roots are associated with diverse communities of endophytic bacteria which do not exert adverse effects. The diversity of bacterial endophytes associated with ginseng roots cultivated in three different areas in Korea was investigated. Sixty-three colonies were isolated from the interior of ginseng roots. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolates belonged to three major phylogenetic groups: the high G+C Gram-positive bacteria (HGCGPB), low G+C Gram-positive bacteria (LGCGPB), and the Proteobacteria. The dominant species at the three different ginseng growing areas were: HGCGPB at Ganghwa (55.0%), LGCGPB at Geumsan (45.5%), and Proteobacteria at Jinan (61.9%). Most cellulase-, xylanase-, and pectinase-producing colonies among the isolates belong to the LGCGPB group, except for Pectobacterium carotovora which belonged to the Proteobacteria. The 13 isolates belonging to LGCGPB and Proteobacteria were assessed for their antifungal activity against phytopathogenic fungi such as Rhizoctonia solani. Among them, Paenibacillus polymyxa GS01, Bacillus sp. GS07, and Pseudomonas poae JA01 show potential activity as biocontrol agents against phytopathogenic fungi. Finally, most of the low G+C Gram-positive bacteria with antifungal activity against phytopathogenic microorganisms showed cellulolytic enzyme activity while some Proteobacteria with the antifungal activity and the high G+C Gram-positive bacteria did not show any cellulolytic activity. PMID:17492474

  9. An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products

    PubMed Central

    Mousa, Walaa K.; Schwan, Adrian; Davidson, Jeffrey; Strange, Philip; Liu, Huaizhi; Zhou, Ting; Auzanneau, France-Isabelle; Raizada, Manish N.

    2015-01-01

    Finger millet is an ancient African cereal crop, domesticated 7000 years ago in Ethiopia, reaching India at 3000 BC. Finger millet is reported to be resistant to various fungal pathogens including Fusarium sp. We hypothesized that finger millet may host beneficial endophytes (plant-colonizing microbes) that contribute to the antifungal activity. Here we report the first isolation of endophyte(s) from finger millet. Five distinct fungal species were isolated from roots and predicted taxonomically based on 18S rDNA sequencing. Extracts from three putative endophytes inhibited growth of F. graminearum and three other pathogenic Fusarium species. The most potent anti-Fusarium strain (WF4, predicted to be a Phoma sp.) was confirmed to behave as an endophyte using pathogenicity and confocal microscopy experiments. Bioassay-guided fractionation of the WF4 extract identified four anti-fungal compounds, viridicatol, tenuazonic acid, alternariol, and alternariol monomethyl ether. All the purified compounds caused dramatic breakage of F. graminearum hyphae in vitro. These compounds have not previously been reported to have anti-Fusarium activity. None of the compounds, except for tenuazonic acid, have previously been reported to be produced by Phoma. We conclude that the ancient, disease-tolerant crop, finger millet, is a novel source of endophytic anti-fungal natural products. This paper suggests the value of the crops grown by subsistence farmers as sources of endophytes and their natural products. Application of these natural chemicals to solve real world problems will require further validation. PMID:26539183

  10. Evaluation of Antifungal Activity and Mechanism of Action of Citral against Candida albicans

    PubMed Central

    Leite, Maria Clerya Alvino; Bezerra, André Parente de Brito; de Sousa, Janiere Pereira; Guerra, Felipe Queiroga Sarmento; Lima, Edeltrudes de Oliveira

    2014-01-01

    Candida albicans is a yeast that commensally inhabits the human body and can cause opportunistic or pathogenic infections. Objective. To investigate the antifungal activity of citral against C. albicans. Methodology. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were determined by the broth microdilution techniques. We also investigated possible citral action on cell walls (0.8?M sorbitol), cell membranes (citral to ergosterol binding), the time-kill curve, and biological activity on the yeast's morphology. Results. The MIC and MFC of citral were, respectively, 64?µg/mL and 256?µg/mL. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms of action. In the morphological interference assay, it was observed that the product inhibited pseudohyphae and chlamydoconidia formation. The MIC and the MFC of citral required only 4 hours of exposure to effectively kill 99.9% of the inoculum. Conclusion. Citral showed in vitro antifungal potential against strains of C. albicans. Citral's mechanism of action does not involve the cell wall or ergosterol, and further study is needed to completely describe its effects before being used in the future as a component of new antifungals. PMID:25250053

  11. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species.

    PubMed

    Pinto, Eugénia; Vale-Silva, Luís; Cavaleiro, Carlos; Salgueiro, Lígia

    2009-11-01

    The composition and antifungal activity of clove essential oil (EO), obtained from Syzygium aromaticum, were studied. Clove oil was obtained commercially and analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3 %). MICs, determined according to Clinical and Laboratory Standards Institute protocols, and minimum fungicidal concentration were used to evaluate the antifungal activity of the clove oil and its main component, eugenol, against Candida, Aspergillus and dermatophyte clinical and American Type Culture Collection strains. The EO and eugenol showed inhibitory activity against all the tested strains. To clarify its mechanism of action on yeasts and filamentous fungi, flow cytometric and inhibition of ergosterol synthesis studies were performed. Propidium iodide rapidly penetrated the majority of the yeast cells when the cells were treated with concentrations just over the MICs, meaning that the fungicidal effect resulted from an extensive lesion of the cell membrane. Clove oil and eugenol also caused a considerable reduction in the quantity of ergosterol, a specific fungal cell membrane component. Germ tube formation by Candida albicans was completely or almost completely inhibited by oil and eugenol concentrations below the MIC values. The present study indicates that clove oil and eugenol have considerable antifungal activity against clinically relevant fungi, including fluconazole-resistant strains, deserving further investigation for clinical application in the treatment of fungal infections. PMID:19589904

  12. A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Xue, Jingzhe; Luo, Zhihui; Li, Ping; Ding, Yaping; Cui, Yi; Wu, Qingsheng

    2014-07-01

    Here we reported a residue-free green nanotechnology which synergistically enhance the pesticides efficiency and successively eliminate its residue. We built up a composite antifungal system by a simple pre-treating and assembling procedure for investigating synergy. Investigations showed 0.25 g/L ZnO nanoparticles (NPs) with 0.01 g/L thiram could inhibit the fungal growth in a synergistic mode. More importantly, the 0.25 g/L ZnO NPs completely degraded 0.01 g/L thiram under simulated sunlight irradiation within 6 hours. It was demonstrated that the formation of ZnO-thiram antifungal system, electrostatic adsorption of ZnO NPs to fungi cells and the cellular internalization of ZnO-thiram composites played important roles in synergy. Oxidative stress test indicated ZnO-induced oxidative damage was enhanced by thiram that finally result in synergistic antifungal effect. By reducing the pesticides usage, this nanotechnology could control the plant disease economically, more significantly, the following photocatalytic degradation of pesticide greatly benefit the human social by avoiding negative influence of pesticide residue on public health and environment.

  13. Antifungal starter culture for packed bread: influence of two storage conditions.

    PubMed

    Gerez, Carla L; Fornaguera, María J; Obregozo, Mariano D; Font de Valdez, Graciela; Torino, María I

    2015-01-01

    In this study, we analyzed the conservation of a semi-liquid bio-preserver (SL778) developed with Lactobacillus plantarum CRL 778, a lactic acid bacterium (LAB) having antifungal activity. The characteristics of the SL778 starter remained stable during a 14-day storage at 4°C. At -20°C, cell viability and organic acid concentration showed a significant (p<0.05) decrease after 7 days. These differences observed between the storage temperatures tested were reflected in the acidification activity of SL778 during dough fermentation. However, SL778 maintained its antifungal efficacy up to a 14-day storage at both temperatures. Sensory attributes (acidic and spicy tastes and acidic smell) of breads manufactured with starter SL778 (stored at 4 or -20°C) were evaluated. No undesirable difference was detected with respect to bread control without SL778 and bread manufactured with SL778 (stored at 4 or -20°C). In conclusion, the SL778 semi-liquid bio-preserver can be stored at 4 or -20°C without modifying its antifungal activity during 14 days. PMID:25896466

  14. Biochemical characterization of fruit-specific pathogenesis-related antifungal protein from basrai banana.

    PubMed

    Yasmin, Nusrat; Saleem, Mahjabeen

    2014-01-01

    Pathogenesis-related/thaumatin like (PR-5/TL) antifungal protein from basrai banana was purified by using a simple protocol consisting of ammonium sulphate precipitation, affinity chromatography (Affi-gel blue gel), Q-Sepharose chromatography and gel filtration on Sephadex G-75. The purified protein with acidic character (pI 6.67) has molecular weight of 21.155 kDa, as determined by MALDI-TOF mass spectrometry. The purified protein shared N-terminal sequence homology with other TLPs. Crude banana extract inhibited the growth of Fusarium oxysporum, Aspergillus niger, Aspergillus fumigatus and Trichoderma viride with IC?? values (determined by Probit analysis) 15 ?M (slope=0.086, ?(2)=17.843, P=0.033), 17 ?M (slope=0.183, ?(2)=61.533, P=0.011), 6.5 ?M (slope=0.211, ?(2)=14.380, P=0.023) and 29.11 ?M (slope=0.072, ?(2)=45.768, P=0.014). The purified antifungal protein repressed the growth of F. oxysporum, A. niger, A. fumigatus and T. viride with IC?? values 9.7 ?M (slope=0.056, ?(2)=11.538, P=0.021), 11.83 ?M (slope=0.127, ?(2)=42.82, P=0.00), 4.61 ?M (slope=0.150, ?(2)=10.199, P=0.017) and 21.43 ?M (slope=0.053, ?(2)=33.693, P=0.00), respectively. The IC50 values of antifungal activity of crude banana extract were higher than the purified antifungal protein. It indicated that proteins in crude banana extract have antagonistic effect on the fungal growth. White bread is particularly vulnerable by fungal pathogens. Purified antifungal protein suppressed the growth of Aspergillus phoenicis and Aspergillus flavus on white bread suggesting that this protein can be used as a preservative in the bakery industry as well as in other relevant food processing industries. PMID:24192113

  15. Systemic Antifungal Prescribing in Neonates and Children: Outcomes from the Antibiotic Resistance and Prescribing in European Children (ARPEC) Study

    PubMed Central

    Versporten, A.; Doerholt, K.; Warris, A.; Roilides, E.; Sharland, M.; Bielicki, J.; Goossens, H.

    2014-01-01

    The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n = 355) and amphotericin B deoxycholate (n = 195). The most common indications for antifungal administration in children were medical prophylaxis (n = 325), empirical treatment of febrile neutropenia (n = 122), and treatment of confirmed or suspected IFI (n = 100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n = 103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n = 371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children. PMID:25403672

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

    PubMed

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 ?g/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi. PMID:25394604

  17. Purification and identification of a novel antifungal protein secreted by Penicillium citrinum from the Southwest Indian Ocean.

    PubMed

    Wen, Chao; Guo, Wenbin; Chen, Xinhua

    2014-10-01

    A novel antifungal protein produced by the fungal strain Penicillium citrinum W1, which was isolated from a Southwest Indian Ocean sediment sample, was purified and characterized. The culture supernatant of P. citrinum W1 inhibited the mycelial growth of some plant pathogenic fungi. After saturation of P. citrinum W1 culture supernatants with ammonium sulfate and ion-exchange chromatography, an antifungal protein (PcPAF) was purified. The N-terminal amino acid sequence analysis showed that PcPAF might be an unknown antifungal protein. PcPAF displayed antifungal activity against Trichoderma viride, Fusarium oxysporum, Paecilomyces variotii, and Alternaria longipes at minimum inhibitory concentrations of 1.52, 6.08, 3.04, and 6.08 µg/disc, respectively. PcPAF possessed high thermostability and had a certain extent of protease and metal ion resistance. The results suggested that PcPAF may represent a novel antifungal protein with potential application in controlling plant pathogenic fungal infection. PMID:24931500

  18. Antifungal lipids produced by lactobacilli and their structural identification by normal phase LC/atmospheric pressure photoionization?MS/MS.

    PubMed

    Black, Brenna A; Sun, Chenxing; Zhao, Yuan Yuan; Gänzle, Michael G; Curtis, Jonathan M

    2013-06-01

    Lactobacillus hammesii converts linoleic acid into an antifungal hydroxy fatty acid. High speed counter-current chromatography (HSCCC) using a hexane/ethyl acetate/methanol/water solvent system [3.5:1.5:3:2 (v/v/v/v)] allowed isolation of the antifungal hydroxy fatty acid. A method was developed for characterization of antifungal hydroxy fatty acids using normal phase liquid chromatography combined with atmospheric pressure photoionization-tandem mass spectrometry (LC/APPI-MS/MS). The position of unsaturations and hydroxyl groups was determined directly from crude lipid extracts and their hydroxylated derivatives. The antifungal compounds were identified as a racemic mixture of 10-hydroxy-cis-12-octadecenoic and 10-hydroxy-trans-12-octadecenoic acid. Additionally, HSCCC and LC/APPI-MS/MS methods were used to elucidate the pathway of conversion of linoleic acid by Lactobacillus sanfranciscensis , Lactobacillus plantarum , and L. hammesii to hydroxy fatty acids and conjugated linoleic acid. This study links previously reported 10-hydroxy-12-octadecenoic acid producing Lactobacillus strains to antifungal activities. PMID:23706022

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

    PubMed

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

    2015-07-01

    The aim of this study was to determine the putative modes of action of 59 viticultural yeasts (31 Saccharomyces and 28 non-Saccharomyces) that inhibited fungi isolated from sour and grey rot in grapes. Inhibition of fungal mycelial growth by metabolites, enzyme activities (laminarinases, chitinases), antifungal volatiles, competition for nutrients (siderophores, Niche Overlap Index (NOI)), inhibition of fungal spore germination and decreased germinal tube length and induction of resistance were assayed. Biofungicide yeasts were classified into "antifungal patterns", according to their mechanisms of action. Thirty isolates presented at least two of the mechanisms assayed. We propose that inhibition of fungal mycelial growth by metabolites, laminarinases, competition for nutrients, inhibition of fungal spore germination and decreased germinal tube length, and antifungal volatiles by Saccharomyces and non-Saccharomyces viticultural yeasts is used as putative biocontrol mechanisms against phytopathogenic fungi. Twenty-four different antifungal patterns were identified. Siderophore production (N)and a combination of siderophore production and NOI>0.92 (M)were the most frequent antifungal patterns observed in the biofungicide yeasts assayed. Elucidation of these mechanisms could be useful for optimization of an inoculum formulation, resulting in a more consistent control of grey and sour rot with Saccharomyces and non-Saccharomyces biocontrol yeasts. PMID:25863340

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

    PubMed

    Ye, X Y; Ng, T B

    2002-01-18

    From the seeds of the pinto bean (Phaseolus vulgaris cv. pinto), a chitinase and a novel antifungal protein, both with the ability of markedly augmenting nitrite production by murine peritoneal macrophages, were isolated. The antifungal proteins, designated phasein A and phasein B, exhibited molecular weights of 28 and 32 kDa, respectively. Phaseins A and B were adsorbed on Affi-gel blue gel and CM-Sepharose and were eluted as adjacent peaks from CM-Sepharose. Phasein A demonstrated potent antifungal activity toward Fusarium oxysporum and Physalospora piricola. Phasein B was more potent than phasein A toward P. piricola but less potent than phasein A toward F. oxysporum and Rhizoctonia solani. Both antifungal proteins inhibited the activity of HIV-1 reverse transcriptase and translation in a rabbit reticulocyte lysate system, with phasein B being more potent. Nitrite production by mouse macrophages was greatly boosted in the presence of both phaseins A and B, although the effect of phasein A was more prominent. The bioactivities of phaseins were in general potent compared with those of other antifungal proteins. PMID:11785974

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-11-01

    The centipede Scolopendra subspinipes mutilans has been a medically important arthropod species by using it as a traditional medicine for the treatment of various diseases. In this study, we derived a novel lactoferricin B like peptide (LBLP) from the whole bodies of adult centipedes, S. s. mutilans, and investigated the antifungal effect of LBLP. LBLP exerted an antifungal and fungicidal activity without hemolysis. To investigate the antifungal mechanism of LBLP, a membrane study with propidium iodide was first conducted against Candida albicans. The result showed that LBLP caused fungal membrane permeabilization. The assays of the three dimensional flow cytometric contour plot and membrane potential further showed cell shrinkage and membrane depolarization by the membrane damage. Finally, we confirmed the membrane-active mechanism of LBLP by synthesizing model membranes, calcein and FITC-dextran loaded large unilamellar vesicles. These results showed that the antifungal effect of LBLP on membrane was due to the formation of pores with radii between 0.74nm and 1.4nm. In conclusion, this study suggests that LBLP exerts a potent antifungal activity by pore formation in the membrane, eventually leading to fungal cell death. PMID:23896552

  3. The antifungal activity of Sarcococca saligna ethanol extract and its combination effect with fluconazole against different resistant Aspergillus species.

    PubMed

    Mollazadeh Moghaddam, Kamyar; Arfan, Mohammad; Rafique, Jamal; Rezaee, Sassan; Jafari Fesharaki, Parisa; Gohari, Ahmad Reza; Shahverdi, Ahmad Reza

    2010-09-01

    Microbial resistance is a major drawback in chemotherapy of microbial or fungal infection disease. In this study, the antifungal activity of ethanol extract of a selected plant (Sarcococca saligna) has been investigated against clinical isolates of Aspergillus niger, Aspergillus treus, Aspergillus flavus, and Aspergillus fumigatus. Also, the enhancement of the antifungal activity of fluconazole by this extract was further evaluated against mentioned test strains. Conventional disk diffusion method was used to assay the antifungal activity of S. saligna ethanol extract in the absence and presence of fluconazole. The highest antifungal activity was observed against A. treus. The ethanol extract of S. saligna enhanced the antifungal activity of fluconazole against A. niger and A. treus and A. flavus. At the highest tested contents (4 mg/disk), 1.15-, 0.64-, and 2.47-fold increases in inhibition zone surface area were observed for A. niger, A. treus, and A. flavus, respectively. However, no enhancing effect was observed for this plant extract against Aspergillus fumigates at tested contents (0.5, 1, 2, 3, and 4 mg/disk). In a separate experiment, the general cytotoxicity of the ethanol extract of S. saligna was examined with brine shrimp assay. This plant extract showed low cytotoxicity against Artemia salina (LC(50) = 186 microg/ml). PMID:19685213

  4. Enhanced Antifungal Activity by Ab-Modified Amphotericin B-Loaded Nanoparticles Using a pH-Responsive Block Copolymer

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Dai, Jingjing; Xie, Jun; Zhu, Yongqiang; Zhu, Ming; Wang, Zhi; Xie, Chunmei; Yao, Aixia; Liu, Tingting; Wang, Xiaoyu; Chen, Li; Jiang, Qinglin; Wang, Shulei; Liang, Yong; Xu, Congjing

    2015-06-01

    Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Amphotericin B (AMB), with broad-spectrum antifungal activity, has long been recognized as a powerful fungicidal drug, but its clinical toxicities mainly nephrotoxicity and poor solubility limit its wide application in clinical practice. The fungal metabolism along with the host immune response usually generates acidity at sites of infection, resulting in loss of AMB activity in a pH-dependent manner. Herein, we developed pH-responsive AMB-loaded and surface charge-switching poly( d, l-lactic- co-glycolic acid)- b-poly( l-histidine)- b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for resolving the localized acidity problem and enhance the antifungal efficacy of AMB. Moreover, we modified AMB-encapsulated PLGA-PLH-PEG nanoparticles with anti- Candida albicans antibody (CDA) (CDA-AMB-NPs) to increase the targetability. Then, CDA-AMB-NPs were characterized in terms of physical characteristics, in vitro drug release, stability, drug encapsulation efficiency, and toxicity. Finally, the targetability and antifungal activity of CDA-AMB-NPs were investigated in vitro /in vivo. The result demonstrated that CDA-AMB-NPs significantly improve the targetability and bioavailability of AMB and thus improve its antifungal activity and reduce its toxicity. These NPs may become a good drug carrier for antifungal treatment.

  5. Enhanced Antifungal Activity by Ab-Modified Amphotericin B-Loaded Nanoparticles Using a pH-Responsive Block Copolymer.

    PubMed

    Tang, Xiaolong; Dai, Jingjing; Xie, Jun; Zhu, Yongqiang; Zhu, Ming; Wang, Zhi; Xie, Chunmei; Yao, Aixia; Liu, Tingting; Wang, Xiaoyu; Chen, Li; Jiang, Qinglin; Wang, Shulei; Liang, Yong; Xu, Congjing

    2015-12-01

    Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Amphotericin B (AMB), with broad-spectrum antifungal activity, has long been recognized as a powerful fungicidal drug, but its clinical toxicities mainly nephrotoxicity and poor solubility limit its wide application in clinical practice. The fungal metabolism along with the host immune response usually generates acidity at sites of infection, resulting in loss of AMB activity in a pH-dependent manner. Herein, we developed pH-responsive AMB-loaded and surface charge-switching poly(D,L-lactic-co-glycolic acid)-b-poly(L-histidine)-b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for resolving the localized acidity problem and enhance the antifungal efficacy of AMB. Moreover, we modified AMB-encapsulated PLGA-PLH-PEG nanoparticles with anti-Candida albicans antibody (CDA) (CDA-AMB-NPs) to increase the targetability. Then, CDA-AMB-NPs were characterized in terms of physical characteristics, in vitro drug release, stability, drug encapsulation efficiency, and toxicity. Finally, the targetability and antifungal activity of CDA-AMB-NPs were investigated in vitro/in vivo. The result demonstrated that CDA-AMB-NPs significantly improve the targetability and bioavailability of AMB and thus improve its antifungal activity and reduce its toxicity. These NPs may become a good drug carrier for antifungal treatment. PMID:26061446

  6. Antifungal activity against Candida albicans of starch Pickering emulsion with thymol or amphotericin B in suspension and calcium alginate films.

    PubMed

    Cossu, Andrea; Wang, Min S; Chaudhari, Amol; Nitin, Nitin

    2015-09-30

    Conventional antifungal treatments against Candida albicans in the oral cavity often result in increased cytotoxicity. The goal of this study was to determine the potential of starch Pickering emulsion as a delivery vehicle for an antifungal natural phenolic compound such as thymol in simulated saliva fluid (SSF) compared to amphotericin B. An oil-in-water (o/w) emulsion was stabilized using starch particles. Physical stability of the emulsion and disruption induced by ?-amylase activity in SSF was evaluated. Encapsulated thymol in o/w emulsion was compared to encapsulated amphotericin B for antifungal activity against C. albicans in suspension using emulsions or zone inhibition assay on agar plates using emulsions dispersed in alginate films. Results showed that the emulsions were stable for at least three weeks. Digestion of the emulsion by ?-amylase led to coalescence of emulsion droplets. The antifungal activity of thymol and amphotericin B in emulsion formulation was enhanced upon incubation with ?-amylase. Results from the zone inhibition assay demonstrated efficacy of the emulsions dispersed in alginate films. Interestingly, addition of ?-amylase to the alginate films resulted in a decreased inhibitory effect. Overall, this study showed that starch Pickering emulsions have a potential to deliver hydrophobic antifungal compounds to treat oral candidiasis. PMID:26231107

  7. Tandem combination of Trigonella foenum-graecum defensin (Tfgd2) and Raphanus sativus antifungal protein (RsAFP2) generates a more potent antifungal protein.

    PubMed

    Karri, Vasavirama; Bharadwaja, Kirti Pulugurtha

    2013-11-01

    Plant defensins are small (45 to 54 amino acids) positively charged antimicrobial peptides produced by the plant species, which can inhibit the growth of a broad range of fungi at micro-molar concentrations. These basic peptides share a common characteristic three-dimensional folding pattern with one ?-helix and three ?-sheets that are stabilized by eight disulfide-linked cysteine residues. Instead of using two single-gene constructs, it is beneficial when two effective genes are made into a single fusion gene with one promoter and terminator. In this approach, we have linked two plant defensins namely Trigonella foenum-graecum defensin 2 (Tfgd2) and Raphanus sativus antifungal protein 2 (RsAFP2) genes by a linker peptide sequence (occurring in the seeds of Impatiens balsamina) and made into a single-fusion gene construct. We used pET-32a+ vector system to express Tfgd2-RsAFP2 fusion gene with hexahistidine tag in Escherichia coli BL21 (DE3) pLysS cells. Induction of these cells with 1 mM IPTG achieved expression of the fusion protein. The solubilized His6-tagged recombinant fusion protein was purified by immobilized-metal (Ni2+) affinity column chromatography. The final yield of the fusion protein was 500 ng/?L. This method produced biologically active recombinant His6-tagged fusion protein, which exhibited potent antifungal action towards the plant pathogenic fungi (Botrytis cinerea, Fusarium moniliforme, Fusarium oxysporum, Phaeoisariopsis personata and Rhizoctonia solani along with an oomycete pathogen Phytophthora parasitica var nicotianae) at lower concentrations under in vitro conditions. This strategy of combining activity of two defensin genes into a single-fusion gene will definitely be a promising utility for biotechnological applications. PMID:24022215

  8. Production of anti-fungal volatiles by non-pathogenic Fusarium oxysporum and its efficacy in suppression of verticillium wilt of cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: The study aimed to identify volatile organic compounds (VOCs) produced by the non-pathogenic Fusarium oxysporum (Fo) strain CanR-46, and to determine the anti-fungal spectrum and the control efficacy of the Fo-VOCs. Methods: The Fo-VOCs were identified by GC-MS. The antifungal activity of the...

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

    PubMed Central

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

    2014-01-01

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

  10. Antifungal susceptibility profiles of Candida isolates from a prospective survey of invasive fungal infections in Italian intensive care units.

    PubMed

    Tortorano, Anna Maria; Prigitano, Anna; Dho, Giovanna; Grancini, Anna; Passera, Marco

    2012-03-01

    The antifungal susceptibility pattern of 302 Candida isolates collected during an Italian survey on invasive fungal infections in an intensive care setting was investigated. The results were correlated with some epidemiological data and compared with the antifungal profiles obtained in a previous survey. No resistance to echinocandins was detected. The overall resistance levels to fluconazole, posaconazole and voriconazole were 12.6, 6.0 and 7.1?%, respectively. Candida tropicalis and Candida parapsilosis accounted for more than half of all the fluconazole resistant isolates. Reduced susceptibility to fluconazole is not uncommon among isolates (12.3?%) and appears to be increasing, particularly among C. parapsilosis isolates, which showed an increase in resistant isolates from 2?% in the 1990s to 25.8?% in the present study. Routine antifungal susceptibility testing of this species is therefore recommended. PMID:22096131

  11. [Evaluation of antifungal effects of a traditional medicine containing 17 components on Trichophyton verrucosum and Malassezia pachydermatis by microdilution].

    PubMed

    Nishikata, Naoko; Nakamori, Kentaro; Sueyoshi, Masuo; Takahashi, Hideo; Yuji, Hiroyuki; Sano, Ayako

    2011-01-01

    The minimum inhibitory concentration(MIC)of a traditional medicine containing 17 components against 9 strains of Trichophyton verrucosum and 13 strains of Malassezia pachydermatis was determined using a method recommended by the Clinical and Laboratory Standards Institute(CLSI). We also measured the MIC of each of the 17 components using the same method, and identified the main antifungal components.In order to evaluate MIC as a parameter of the antifungal effects using the microdilution method, we prepared 10% working solutions from 10% (w/v)medicines. The geometric mean MIC of the medicinal extract against T. verrucosum was 2.51%, and that against M. pachydermatis was 2.25%. The components that exhibited antifungal effects were Rheum palmatum, Glycyrrhiza uralensis, Magnolia obovata, Phellodendron amurense, and Geranium thunbergii. PMID:21891983

  12. Vitis vinifera canes, a new source of antifungal compounds against Plasmopara viticola, Erysiphe necator, and Botrytis cinerea.

    PubMed

    Schnee, Sylvain; Queiroz, Emerson F; Voinesco, Francine; Marcourt, Laurence; Dubuis, Pierre-Henri; Wolfender, Jean-Luc; Gindro, Katia

    2013-06-12

    Methanolic and ethanolic crude extracts of Vitis vinifera canes exhibited significant antifungal activity against the three major fungal pathogens affecting grapevines, Plasmopara viticola, Erysiphe necator and Botrytis cinerea. The active extracts were analyzed by LC-PDA-ESI-MS, and selected compounds were identified. Efficient targeted isolation using medium-pressure liquid chromatography afforded six pure constituents in one step. The structures of the isolated compounds were elucidated by NMR and HRMS. Six identified compounds (ampelopsin A, hopeaphenol, trans-resveratrol, ampelopsin H, ?-viniferin, and E-vitisin B) presented antifungal activities against P. viticola. ?-Viniferin also exhibited a low antifungal activity against B. cinerea. None of the identified compounds inhibited the germination of E. necator. The potential to develop a novel natural fungicide against the three major fungal pathogens affecting V. vinifera from viticulture waste material is discussed. PMID:23730921

  13. Antitumor and antifungal activities of organic extracts of seacucumber Holothuria atra from the southeast coast of India

    NASA Astrophysics Data System (ADS)

    Dhinakaran, Devaraj Isaac; Lipton, Aaron Premnath

    2015-02-01

    In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cucumber Holothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such as Trichoderma viride, Aspergillus niger, Aspergillus flavis, Candida albicans and Penicillium chrysogenum. Relatively high antifungal activity was seen against Candida albicans at 100 ?L-1 concentration of extracts. Zone of inhibition was measured at 18 mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated with H. atra extract at concentrations 0.078-10mg mL-1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber ( H. atra) showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

  14. An update on antifungal targets and mechanisms of resistance in Candida albicans.

    PubMed

    Akins, Robert A

    2005-06-01

    Much progress has been made in the last decade in identifying genes responsible for antifungal resistance in Candida albicans. Attention has focused on five major C. albicans genes: ABC transporter genes CDR1 and CDR2, major facilitator efflux gene MDR1, and ergosterol biosynthesis genes ERG11 and ERG3. Resistance involves mutations in 14C-lanosterol demethylase, targeted by fluconazole (FLZ) and encoded by ERG11, and mutations that up-regulate efflux genes that probably efflux the antifungals. Mutations that affect ERG3 mutations have been understudied as mechanism resistance among clinical isolates. In vitro resistance in clinical isolates typically involves step-wise mutations affecting more than one of these genes, and often unidentified genes. Different approaches are needed to identify these other genes. Very little is understood about reversible adaptive resistance of C. albicans despite its potential clinical significance; most clinical failures to control infections other than oropharyngeal candidiasis (OPC) occur with in vitro susceptible strains. Tolerance of C. albicans to azoles has been attributed to the calcineurin stress-response pathway, offering new potential targets for next generation antifungals. Recent studies have identified genes that regulate CDR1 or ERG genes. The focus of this review is C. albicans, although information on Saccharomyces cerevisiae or Candida glabrata is provided in areas in where Candida research is underdeveloped. With the completion of the C. albicans genomic sequence, and new methods for high throughput gene overexpression and disruption, rapid progress towards understanding the regulation of resistance, novel resistance mechanisms, and adaptive resistance is expected in the near future. PMID:16110776

  15. Clerodane type diterpene as a novel antifungal agent from Polyalthia longifolia var. pendula.

    PubMed

    Bhattacharya, Asish K; Chand, Hemender R; John, Jyothis; Deshpande, Mukund V

    2015-04-13

    Bioactivity-guided chemical examination of methanolic extract of leaves of Polyalthia longifolia var. pendula led to the isolation of the active constituent, a diterpene 1 which was identified as 16?-hydroxycleroda-3,13(14)Z-dien-15,16-olide on the basis of its spectral data. Among the tested strains, diterpene 1 was found to exhibit antifungal activities having MIC90 values of 50.3, 100.6 and 201.2 ?M against Candida albicans NCIM3557, Cryptococcus neoformans NCIM3542 (human pathogens) and Neurospora crassa NCIM870 (saprophyte), respectively. Initial, structure-activity-relationship (SAR) data generated by synthesizing some derivatives revealed that the double bond between C3-C4 and the free hydroxyl group at C16 are crucial for the antifungal activity of the diterpene 1. The mode of action of 1 in C. albicans is due to compromised cell membrane permeability and also probably due to disruption of cell wall structures. The red blood cell haemolysis of all the compounds (1-4) did not show any significant haemolysis and was found to be less than 15% for all the compounds when tested at highest concentration, i.e. 1200 ?M. Interestingly, all the tested compounds inhibited Y-H transition in dimorphic C. albicans NCIM3557 at much lower concentration than their MIC90 values. Determination of ROS generation by diterpene 1 using DCFH-DA and DHR123 (dihydrorhodamine) staining of C. albicans NCIM3557 indicated production of intracellular ROS as a mechanism of antifungal activity. PMID:25747495

  16. Antibacterial, anti-fungal and phytotoxic activities of Ferula narthex Boiss.

    PubMed

    Bashir, Shumaila; Alam, Mahboob; Ahmad, Bashir; Aman, Akhtar

    2014-11-01

    Crude methanolic extract of roots, aerial parts and its subsequent fractions of Ferula narthex Boiss were tested for antibacterial, anti-fungal and phytotoxic activities. Crude methanolic extract of roots and its fractions showed significant antibacterial effect against P.aeruginosa (86.95%, 73.91, 69.59, 78.26 & 73.91%) represented by percent inhibition except ethyl acetate (EtoAc) fraction. The EtoAc fraction of roots and aerial parts showed significant activity against E. coli (80%), S. typhi (81.2 & 81.25%) and S. pneumoniae (80%). The n-hexane, chloroform and aqueous fractions of aerial parts showed significant activity against P. aeruginosa (78.26, 69.56 & 73.91%). Following fungal strains (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, C. glabrata) were also used for anti-fungal activity. Among tested samples only crude methanol extract of roots, n-hexane and chloroform fraction showed moderate anti-fungal activity against M. canis (40, 35 & 30%) represented by percent inhibition. The remaining fractions showed no effect on tested fungi. Different oils fractions were also tested against above fungal strains. Fraction I, II & V showed mild to moderate activity against M. canis (40, 40 & 25%). Phytotoxic effect of tested samples of roots, aerial part and its fractions showed concentration dependent growth inhibition. Maximum phytotoxic effect was noted for n-hexane and aqueous fraction (50% growth inhibition). The remaining tested samples showed mild effect on growth of Lemna minor plant. PMID:25362591

  17. Chemosensitisation of drug-resistant and drug-sensitive yeast cells to antifungals.

    PubMed

    Cernicka, Jana; Kozovska, Zuzana; Hnatova, Martina; Valachovic, Martin; Hapala, Ivan; Riedl, Zsuzsanna; Hajós, György; Subik, Julius

    2007-02-01

    Multidrug resistance in yeast results from overexpression of genes encoding drug efflux transporters owing to gain-of-function mutations in transcription factors regulating their expression. We have screened a library of synthetic compounds for modulators of drug resistance using the multidrug-resistant Saccharomyces cerevisiae pdr3-9 mutant strain. One of the compounds, 7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine (CTBT), displayed weak antifungal activity and strongly inhibited the growth of yeast cells in combination with subinhibitory concentrations of other antifungals with a different mode of action. Biological activity of CTBT was demonstrated in Saccharomyces, Kluyveromyces and Candida yeast species grown on solid and in liquid media. The chemosensitising effect of CTBT, manifested as increased antifungal activity of fluconazole, was demonstrated in yeast mutant strains with deleted genes encoding the major multidrug resistance transcription factors Yap1p, Pdr1p and Pdr3p as well as the drug efflux pumps Pdr5p and Snq2p in S. cerevisiae or their counterparts in Candida albicans and Candida glabrata, named Cdr1p and Mdr1p, respectively. Importantly, CTBT also increased the sensitivity to fluconazole in multidrug-resistant cells overexpressing the efflux pumps. Yeast cells grown in the presence of subinhibitory concentrations of CTBT exhibited an altered sterol composition and a slightly enhanced accumulation of Rhodamine 6G, which suggests that the plasma membrane plays a role in sensitisation. This novel chemosensitisation by CTBT that can overcome multidrug resistance in yeast may prove useful in combined treatment of infections caused by drug-resistant fungal pathogens. PMID:17204400

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

    PubMed Central

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

    2014-01-01

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

  19. Molecular Identification, Antifungal Susceptibility Profile, and Biofilm Formation of Clinical and Environmental Rhodotorula Species Isolates

    PubMed Central

    Nunes, Jorge Meneses; Bizerra, Fernando César; Ferreira, Renata Carmona e

    2013-01-01

    Rhodotorula species are emergent fungal pathogens capable of causing invasive infections, primarily fungemia. They are particularly problematic in immunosuppressed patients when using a central venous catheter. In this study, we evaluated the species distribution of 51 clinical and 8 environmental Rhodotorula species isolates using the ID32C system and internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing and biofilm formation capability using a crystal violet staining assay were performed. Using ITS sequencing as the gold standard, the clinical isolates were identified as follows: 44 R. mucilaginosa isolates, 2 R. glutinis isolates, 2 R. minuta isolates, 2 R. dairenensis isolates, and 1 Rhodosporidium fluviale isolate. The environmental isolates included 7 R. mucilaginosa isolates and 1 R. slooffiae isolate. Using the ID32C system, along with a nitrate assimilation test, only 90.3% of the isolates tested were correctly identified. In the biofilm formation assay, R. mucilaginosa and R. minuta exhibited greater biofilm formation ability compared to the other Rhodotorula species; the clinical isolates of R. mucilaginosa showed greater biofilm formation compared to the environmental isolates (P = 0.04). Amphotericin B showed good in vitro activity (MIC ? 1 ?g/ml) against planktonic cells, whereas voriconazole and posaconazole showed poor activity (MIC50/MIC90, 2/4 ?g/ml). Caspofungin and fluconazole MICs were consistently high for all isolates tested (?64 ?g/ml and ? 4 ?g/ml, respectively). In this study, we emphasized the importance of molecular methods to correctly identify Rhodotorula species isolates and non-R. mucilaginosa species in particular. The antifungal susceptibility profile reinforces amphotericin B as the antifungal drug of choice for the treatment of Rhodotorula infections. To our knowledge, this is the first study evaluating putative differences in the ability of biofilm formation among different Rhodotorula species. PMID:23114761

  20. In Vitro Analyses of Mild Heat Stress in Combination with Antifungal Agents against Aspergillus fumigatus Biofilm

    PubMed Central

    Zeng, Rong; Li, Min; Chen, Qing; Wang, Le; Zhan, Ping; Wang, Chong; Lv, Guixia; Shen, Yongnian

    2014-01-01

    Aspergillus fumigatus biofilms still present a challenge for effective treatment in clinical settings. While mild heat stress has been introduced as a treatment for infectious diseases, the effectiveness of mild heat stress on A. fumigatus biofilm formation and antifungal susceptibility is still unknown. In the present study, confocal laser scanning microscopy (CLSM) was used to image and quantify Aspergillus fumigatus biofilm formation under three different regimens of continuous mild heat stress: at 37, 39, and 41°C. Furthermore, fungal growth has been investigated under the above conditions in combination with antifungal drugs (amphotericin B [AMB], micafungin [MCF], and voriconazole [VOC]) at early and late stages. CLSM analysis showed that higher temperatures induce earlier germination and greater hyphal elongation but poorer polar growth and reduced biofilm thickness. In the early stage of biofilm formation, the combination of treatment at 39 or 41°C with MCF or VOC produced no visible difference in biomass formation from similar treatments at 37°C with the same drug. Interestingly, AMB treatment at 37°C inhibited early stage biofilm formation to a much greater extent than at 39 and 41°C. At the late stage of biofilm formation, the mild heat treatments at 39 and 41°C with AMB, MCF, and VOC inhibited biomass formation compared to that at 37°C. The present data show that mild heat stress has a negative regulatory effect on biofilm formation in vitro, and antifungal drug improvement with mild heat treatment at late-stage biofilm formation provides useful indications of possible effective strategies for clinical management of aspergillosis. PMID:24342649

  1. Optimization of antifungal lipopeptide production from Bacillus sp. BH072 by response surface methodology.

    PubMed

    Zhao, Xin; Han, Ye; Tan, Xi-qian; Wang, Jin; Zhou, Zhi-jiang

    2014-04-01

    Antifungal lipopeptide produced by Bacillus sp. BH072 was extracted from fermentation liquor and determined as iturin A by liquid chromatography-mass spectrometry (LC-MS). For industrial-scale production, the yield of iturin A was improved by optimizing medium components and fermentation conditions. A one-factor test was conducted; fermentation conditions were then optimized by response surface methodology (RSM) to obtain the following: temperature, 29.5°C; pH 6.45; inoculation quantity, 6.7%; loading volume, 100 ml (in 500 ml flasks); and rotary speed, 150 rpm. Under these conditions, the mass concentration of iturin A was increased from 45.30 mg/ml to 47.87 mg/ml. The following components of the medium were determined: carbon sources (glucose, fructose, sucrose, xylose, rhamnose, and soluble starch); nitrogen sources (peptone, soybean meal, NH4Cl, urea, and ammonium citrate); and metal ions (Zn(2+), Fe(3+), Mg(2+), Mn(2+), Ca(2+), and K(+)). The effects of these components on iturin A production were observed in LB medium. We selected sucrose, soybean meal, and Mg(2+) for RSM to optimize the conditions because of several advantages, including maximum iturin A production, high antifungal activity, and low cost. The optimum concentrations of these components were 0.98% sucrose, 0.94% soybean meal, and 0.93% Mg(2+). After iturin A production was optimized by RSM, the mass concentration reached 52.21 mg/ml. The antifungal specific activity was enhanced from 350.11 AU/mg to 513.92 AU/mg, which was 46.8% higher than the previous result. The present study provides an important experimental basis for the industrial-scale production of iturin A and the agricultural applications of Bacillus sp. BH072. PMID:24535741

  2. Endophytic Bacillus spp. produce antifungal lipopeptides and induce host defence gene expression in maize.

    PubMed

    Gond, Surendra K; Bergen, Marshall S; Torres, Mónica S; White, James F

    2015-03-01

    Endophytes are mutualistic symbionts within healthy plant tissues. In this study we isolated Bacillus spp. from seeds of several varieties of maize. Bacillus amyloliquifaciens or Bacillus subtilis were found to be present in all maize varieties examined in this study. To determine whether bacteria may produce antifungal compounds, generally lipopeptides in Bacillus spp., bacterial cultures were screened for production of lipopeptides. Lipopeptides were extracted by acid precipitation from liquid cultures of Bacillus spp. Lipopeptide extracts from Bacillus spp. isolated from Indian popcorn and yellow dent corn showed inhibitory activity against Fusarium moniliforme at 500?g per disk. Using MALDI-TOF mass spectrometry we detected the presence of antifungal iturin A, fengycin and bacillomycin in these isolates. PCR amplification also showed the presence of genes for iturin A and fengycin. B. subtilis (SG_JW.03) isolated from Indian popcorn showed strong inhibition of Arabidopsis seed mycoflora and enhanced seedling growth. We tested for the induction of defence gene expression in the host plant after treatment of plants with B. subtilis (SG_JW.03) and its lipopeptide extract using RT-qPCR. Roots of Indian popcorn seedlings treated with a suspension of B. subtilis (SG_JW.03) showed the induction of pathogenesis-related genes, including PR-1 and PR-4, which relate to plant defence against fungal pathogens. The lipopeptide extract alone did not increase the expression of these pathogenesis-related genes. Based on our study of maize endophytes, we hypothesize that, bacterial endophytes that naturally occur in many maize varieties may function to protect hosts by secreting antifungal lipopeptides that inhibit pathogens as well as inducing the up-regulation of pathogenesis-related genes of host plants (systemic acquired resistance). PMID:25497916

  3. Experimental study of the potential for contact sensitization and cross-reaction of imidazole antifungals.

    PubMed

    Nishioka, K; Kurata, K; Asagami, C

    1991-07-01

    We examined the potential for contact sensitization of miconazole nitrate and croconazole hydrochloride and the cross-reaction between them in guinea pigs by the maximization test of Magnusson and Kligman. Contact sensitivity was induced by croconazole hydrochloride in 5 out of 7 animals which, after being injected with 5% croconazole hydrochloride, underwent a closed patch with 25% croconazole hydrochloride. Contact sensitivity was not induced by miconazole nitrate. The 5 animals sensitized to croconazole hydrochloride were tested with 8 other imidazole antifungals and positive reactions were observed to oxiconazole nitrate in 2 of the 5 animals. This response may be a cross-reaction. PMID:1935032

  4. Two new phenylglycol derivatives isolated from Syringa reticulata var. mandshurica and their antifungal activities.

    PubMed

    Xu, Qiong Ming; Liu, Yan Li; Li, Xiao Ran; Feng, Yu Lin; Yang, Shi Lin

    2009-08-01

    Two new phenylglycol derivatives, (S)-(+)-2-(3,4-dihydroxy phenyl)-2-ethoxyl- ethanol and (S)-(+)-2-(3,4-dihydroxy phenyl)-2-acetoxy-ethanol, were isolated from the leaves of Syringa reticulata var. mandshurica, along with two known phenethylols, p-hydroxyl phenethanol and 3,4-dihydroxy phenethanol. The planar structures of the new compounds were established on the basis of their spectral data, and their absolute stereochemistry was established by modified Mosher's method. The two known compounds were identified by comparison of spectral data with published references. The two new compounds showed conspicuous antifungal activities by agar medium assay. PMID:19652414

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

    PubMed

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

    2013-01-01

    Essential oils obtained by hydrodistillation (HD) and microwave-assisted HD (MWHD) of Origanum onites aerial parts were analyzed by GC and GCIMS. Thirty-one constituents representing 98.6% of the water-distilled oil and 52 constituents representing 99.6% of the microwave-distilled oil were identified. Carvacrol (76.8% HD and 79.2% MWHD) and thymol (4.7% HD and 4.4% MWHD) were characterized as major constituents in both essential oils. Separation of carvacrol and thymol was achieved by overpressured layer chromatography. HPTLC and TLC separations were also compared. Essential oils were evaluated for antifungal activity against the strawberry anthracnose-causing fungal plant pathogens Colletotrichum acutatum, C. fragariae, and C. gloeosporioides using a direct overlay bioautography assay. Furthermore, main oil components carvacrol and thymol were then evaluated for antifungal activity; only carvacrol demonstrated nonselective antifungal activity against the three Colletotrichum species. Thymol and carvacrol were subsequently evaluated in a 96-well microdilution broth assay against Phomopsis obscurans, Fusarium oxysporum, three Colletotrichum species, and Botrytis cinerea. No activity was observed against any of the three Colletotrichum species at or below 30 pM. However, thymol demonstrated antifungal activity and produced 31.7% growth inhibition of P. obscurans at 120 h and 0.3 pM, whereas carvacrol appeared inactive. Thymol and carvacrol at 30 pM showed 51.5 and 36.9% growth inhibition of B. cinerea at 72 h. The mechanism of antibacterial activity was studied in a bioautography-based BioArena system. Thymol and carvacrol showed similar inhibition/killing effect against Bacillus subtilis soil bacteria; the action could be enhanced by the formaldehyde generator and transporter copper (II) ions and could be decreased in the presence of L-arginine, a formaldehyde capturer. Results indicated that Origanum essential oils and its major components thymol and carvacrol appear to generate antimicrobial activity through a mechanism of action where formaldehyde and its reaction products are produced. PMID:24645494

  6. A new picrotoxane sesquiterpene from the berries of Baccaurea ramiflora with antifungal activity against Colletotrichum gloeosporioides.

    PubMed

    Pan, Zheng-Hong; Ning, De-Sheng; Huang, Si-Si; Wu, Yun-Fei; Ding, Tao; Luo, Lei

    2015-01-01

    Three picrotoxane sesquiterpenes including one new glycoside and two known constituents, sapidolide A (2) and picrotoximaesin (3), were isolated from the berries of Baccaurea ramiflora. The structure of the new sesquiterpene glycoside, ramifloside (1), was elucidated as 2-one-6?-hydroxy-13-nor-11-picrotoxen-3(15?)-olide 10-O-?-D-glucopyranoside on the basis of extensive spectroscopic analysis. Compounds 1-3 exhibited antifungal activity against Colletotrichum gloeosporioides with MICs of 12.5, 12.5 and 50 ?g/mL. PMID:25583324

  7. An evaluation of antifungal agents for the treatment of fungal contamination in indoor air environments.

    PubMed

    Rogawansamy, Senthaamarai; Gaskin, Sharyn; Taylor, Michael; Pisaniello, Dino

    2015-06-01

    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

  8. Characterization of a new sesquiterpene and antifungal activities of chemical constituents from Dryopteris fragrans (L.) Schott.

    PubMed

    Huang, Yu-Hong; Zeng, Wei-Min; Li, Guo-Yu; Liu, Guo-Qing; Zhao, Dan-Dan; Wang, Jing; Zhang, Yan-Long

    2013-01-01

    One new sesquiterpene and six known compounds were isolated from Dryopteris fragrans (L.) Schot. They were identified as 3-O-?-D-glucopyranosylalbicanol- 11-O-?-D-glucopyranoside (1), dihydroconiferylalcohol (2), (E)-3-(4-hydroxyphenyl)acrylic acid (3), esculetin (4), 5,7-dihydroxy-2-hydroxymethylchromone (5), eriodictyol (6) and isoorientin (7) by UV, MS, 1D-NMR and 2D-NMR spectroscopy. The antifungal activities of the seven isolated compounds were screened. Compounds 2, 3, 4 and 5 showed obvious activities against Microsporum canis and Epidermophyton floccosum. PMID:24451246

  9. An Evaluation of Antifungal Agents for the Treatment of Fungal Contamination in Indoor Air Environments

    PubMed Central

    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

  10. Total Synthesis and Biological Evaluation of an Antifungal Tricyclic o-Hydroxy-p-Quinone Methide Diterpenoid

    PubMed Central

    Huang, Jinhua; Foyle, Dylan; Lin, Xiaorong

    2013-01-01

    A convergent route has been developed to synthesize an antifungal tricyclic o-hydroxy-p-quinone methide diterpenoid and analogs. The Li/naphthalene mediated reductive alkylation was employed for coupling ?-cyclocitral and the corresponding benzyl chloride while the BBr3–mediated one-pot bis-demethylation and intramolecular Friedel Crafts alkylation was used to assemble the tricyclic molecular skeleton. The structure-activity relationship of the diterpenoid was assessed based on anti-proliferation assays of the natural product and analogs against strains of pathogenic yeasts and filamentous fungi. PMID:23957833

  11. A facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity.

    PubMed

    Ramírez-Villalva, Alejandra; González-Calderón, Davir; González-Romero, Carlos; Morales-Rodríguez, Macario; Jauregui-Rodríguez, Bertha; Cuevas-Yáńez, Erick; Fuentes-Benítes, Aydeé

    2015-06-01

    Four novel miconazole analogues (8-11) were synthetized and evaluated for activity against four filamentous fungi (Mucor hiemalis, Aspergillus fumigatus, Trichosporon cutaneum, and Rhizopus oryzae) and eight species of Candida as yeast specimens. Compounds 9 and 10 showed very good activity when evaluated in yeast (MIC 0.112 and 0.163 ?g/mL) compared to the reference compound, itraconazole (MIC 0.067 ?g/mL). The best antifungal activity in filamentous strains was shown by compound 9. Hence compounds 9 and 10 represent new leads for further pharmacomodulation in this series. PMID:25989345

  12. New Ikarugamycin Derivatives with Antifungal and Antibacterial Properties from Streptomyces zhaozhouensis

    PubMed Central

    Lacret, Rodney; Oves-Costales, Daniel; Gómez, Cristina; Díaz, Caridad; de la Cruz, Mercedes; Pérez-Victoria, Ignacio; Vicente, Francisca; Genilloud, Olga; Reyes, Fernando

    2014-01-01

    A bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain Streptomyces zhaozhouensis CA-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1–3) and four known compounds. All the new compounds were structurally related to the known Streptomyces metabolite ikarugamycin (4). Their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (ESI-TOF MS) and 1D and 2D NMR analyses. Compounds 1–3 showed antifungal activity against Aspergillus fumigatus, Candida albicans and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). PMID:25551780

  13. Preparation of some pyrazoline derivatives and evaluation of their antifungal activities.

    PubMed

    Ozdemir, Ahmet; Turan-Zitouni, Gülhan; Kaplancikli, Zafer Asim; Revial, Gilbert; Demirci, Fatih; I?can, Gökalp

    2010-08-01

    The synthesis of a new series of 1-[(benzazole-2-yl)thioacetyl]-3,5-diaryl-2-pyrazoline derivatives was obtained by reacting 1-(chloroacetyl)-3,5-diaryl-pyrazolines with 2-mercaptobenzimidazole/benzoxazole/benzothiazole. The chemical structures of the compounds were elucidated by (1)H-NMR, (13)C-NMR, and FAB(+)-MS spectral data. Their antifungal activities against Candida albicans, Candida glabrata, Candida utilis, Candida tropicalis, Candida krusei, and Candida parapsilosis were investigated. A significant level of activity was observed. PMID:20205628

  14. In vitro interaction of antifungal and antibacterial drugs against Cryptococcus neoformans var. grubii before and after capsular induction.

    PubMed

    Rossato, Luana; Loreto, Érico S; Venturini, Tarcieli P; Azevedo, Maria I; Weiblen, Carla; Botton, Sonia A; Santurio, Janio M; Alves, Sydney H

    2015-11-01

    This study evaluated the synergistic interactions between amphotericin B (AMB) and azithromycin (AZM), daptomycin (DAP), linezolid (LNZ), minocycline (MINO), fluconazole (FLZ), flucytosine (5FC), linezolid (LZD), or tigecycline (TIG) against clinical isolates of Cryptococcus neoformans var. grubii before and after capsule induction. High synergism (>75%) was observed for the combinations, AMB+5FC, AMB+TIG, AMB+AZM, AMB+LZD and AMB+MINO but only in the strains after capsule induction. The results show that the presence of the capsule may lower the minimum inhibitory concentrations (MICs) of antifungal agents, but antimicrobial activity can be improved by combining antifungal and antibacterial agents. PMID:26333356

  15. Isolation and partial characterization of an antifungal protein produced by Bacillus licheniformis BS-3.

    PubMed

    Cui, Tang-Bing; Chai, Hai-Yun; Jiang, Li-Xiang

    2012-01-01

    An antifungal protein produced by Bacillus licheniformis strain BS-3 was purified to homogeneity by ammonium sulfate precipitation, DEAE-52 column chromatography and Sephadex G-75 column chromatography. The purified protein was designated as F2 protein, inhibited the growth of Aspergillus niger, Magnaporthe oryzae and Rhizoctonia solani. F2 protein was a monomer with approximately molecular weight of 31 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gave a single peak on High Performance Liquid Chromatography (HPLC). Using Rhizoctonia solani as the indicator strain, the EC50 of F2 protein was 35.82 µg/mL, displaying a higher antifungal activity in a range of pH 6.0 to pH 10.0, and at a temperature below 70 °C for 30 min. F2 protein was moderately resistant to hydrolysis by trypsin, proteinase K, after which its relative activities were 41.7% and 59.5%, respectively. F2 protein was assayed using various substrates to determine the enzymatic activities, the results showed the hydrolyzing activity on casein, however, no enzymatic activities on colloidal chitin, CM-cellulose, xylan, M. lysodeikticus, and p-nitrophenyl-N-acetylglucosaminide. PMID:22699567

  16. Preliminary study on antifungal effect of commercial essential oils against white rot fungi

    NASA Astrophysics Data System (ADS)

    Khalid, Nurul Izzaty; Baharum, Azizah; Daud, Fauzi

    2015-09-01

    Protecting and preserving wood plastic composite from deterioration caused by fungal attack is a high challenge issue to cater nowadays. The objective of this study was to carry out a screening test towards antifungal effect of essential oil and to investigate the potential of raw materials that will be used as basic material for manufacturing wood plastic composite against white rot fungi. Essential oils from four types of natural products comprising cinnamon, lemongrass, lavender and geranium have been screened for their ability to inhibit five types of white rot fungi species which are Lentinus squarrosulus, Pleuorotus pulmonarius, Lentinus sp., Pleuorotus sajor-caju and Lignosus rhinocerus. The antifungal evaluation showed that no inhibitory effect against tested white rot fungi since the mycelia completely filled the plates. From the observation, mycelia of L. squarrosulus, P. pulmonarius and Lentinus sp. were found to filled the surface of falcon tubes with rubber sawdust after 15 days. Mycelia of L. squarrosulus and P. pulmonarius also were found to completely covered the surface of media that contain polypropylene and maleic anhydride grafted polypropylene on it. Therefore, this report proved that the main materials that will be applicable in manufacturing of wood plastic composite had potential to be degraded by this type of fungal attack.

  17. In vitro anti-leishmanial and anti-fungal effects of new SbIII carboxylates

    PubMed Central

    2011-01-01

    Ring opening of phthalic anhydride has been carried out in acetic acid with glycine, ?-alanine, L-phenylalanine, and 4-aminobenzoic acid to yield, respectively, 2-{[(carboxymethyl)amino]carbonyl}benzoic acid (I), 2-{[(2-carboxyethyl)amino]carbonyl}benzoic acid (II), 2-{[(1-carboxy-2-phenylethyl)amino]carbonyl}benzoic acid (III), and 2-[(4-carboxyanilino)carbonyl]benzoic acid (IV). Compounds I-IV have been employed as ligands for Sb(III) center (complexes V-VIII) in aqueous medium. FTIR and 1H NMR spectra proved the deprotonation of carboxylic protons and coordination of imine group and thereby tridentate behaviour of the ligands as chelates. Elemental, MS, and TGA analytic data confirmed the structural hypothesis based on spectroscopic results. All the compounds have been assayed in vitro for anti-leishmanial and anti-fungal activities against five leishmanial strains L. major (JISH118), L. major (MHOM/PK/88/DESTO), L. tropica (K27), L. infantum (LEM3437), L. mex mex (LV4), and L. donovani (H43); and Aspergillus Flavus, Aspergillus Fumigants, Aspergillus Niger, and Fusarium Solani. Compound VII exhibited good anti-leishmanial as well as anti-fungal impacts comparable to reference drugs.

  18. Antifungal activities of metabolites produced by a termite-associated Streptomyces canus BYB02.

    PubMed

    Zhang, Ying-lao; Li, Shuai; Jiang, Dong-hua; Kong, Li-chun; Zhang, Ping-hua; Xu, Jia-dong

    2013-02-20

    Two main antifungal metabolites resistomycin and tetracenomycin D were isolated and purified from a termite-associated Streptomyces canus BYB02 by column chromatography. The structures of isolated compounds were determined on the basis of extensive spectroscopic analysis. Resistomycin possessed strong activities against mycelial growth of Valsa mali (IC(50) = 1.1 ?g/mL) and Magnaporthe grisea (IC(50) = 3.8 ?g/mL), which were comparable to those of referenced cycloheximide, with IC(50) values of 2.3 and 0.3 ?g/mL, respectively. A further spore germination test showed that resistomycin exhibited potent reduction in spore germination for M. grisea , with an IC(50) value of 5.55 ?g/mL. Finally, the in vivo antifungal activity experiment showed that resistomycin possessed significant preventive efficacy against rice blast, which was more potent than that of referenced carbendazim, with control efficacies of 66.8 and 58.7%, respectively. The present results suggest that resistomycin has potential to be used as a fungicide. PMID:23360202

  19. Species Distribution, Virulence Factors, and Antifungal Susceptibility Among Candida parapsilosis Complex Isolates Recovered from Clinical Specimens.

    PubMed

    da Silva, Beatriz Virgínia; Silva, Larissa Beatriz; de Oliveira, Diego Batista Carneiro; da Silva, Paulo Roberto; Ferreira-Paim, Kennio; Andrade-Silva, Leonardo Euripides; Silva-Vergara, Mario León; Andrade, Anderson Assunçăo

    2015-12-01

    The Candida parapsilosis complex has emerged as an important fungal pathogen. In spite of this, relatively little is known about its characteristics. Thus, the purposes of this study were (1) to determine by BanI-RFLP-assay the occurrence of C. parapsilosis complex species among 81 clinical isolates primarily identified as C. parapsilosis; (2) to evaluate their in vitro production of virulence factors; and (3) to compare their susceptibility profiles, grown as planktonic cells and biofilms, against amphotericin B, fluconazole, voriconazole, and caspofungin by following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Seventy-seven isolates (95 %) were identified as C. parapsilosis sensu stricto, 2 (2.5 %) as C. orthopsilosis, and 2 (2.5 %) as C. metapsilosis. Protease activity was detected in 29 (37.7 %) isolates of C. parapsilosis sensu stricto, whereas only 7 (9.1 %) exhibited phospholipase activity. None of the C. metapsilosis or C. orthopsilosis was able to produce protease or phospholipase. Biofilm production was detected in 35 (43.2 %) isolates, among which 33 were C. parapsilosis sensu stricto and 2 were C. orthopsilosis. Antifungal resistance was uncommon; only one C. metapsilosis was fluconazole resistant. However, biofilm-producing isolates showed a marked resistance to all antifungal agents tested, particularly to voriconazole. This knowledge could be of clinical relevance for guiding therapeutic decisions. PMID:26138435

  20. Effectiveness of Posaconazole in Recalcitrant Fungal Keratitis Resistant to Conventional Antifungal Drugs

    PubMed Central

    Kurna, S. A.; Sengor, T.; Altun, G.; Olcaysu, O. O.; Aki, S. F.; Simsek, M. H.

    2014-01-01

    Purpose. To present the success of posaconazole in two cases with recalcitrant fugal keratitis that were resistant to conventional antifungal drugs. Method. We presented two cases that were treated with posaconazole after the failure of fluconazole or voriconazole, amphotericin B, and natamycin therapy. Case 1 was a 62-year-old man with a history of ocular trauma. He had been using topical fluorometholone and tobramycin. His best corrected visual acuity (BCVA) was hand motion. He had 5.0 × 4.5?mm area of deep corneal ulcer with stromal infiltration. Case 2 was a 14-year-old contact lens user. He had been using topical moxifloxacin, tobramycin, and cyclopentolate. His BCVA was 20/200. He had a 4.0 × 3.0?mm area of pericentral corneal ulcer with deep corneal stromal infiltration and 2?mm hypopyon. Results. Both patients initially received systemic and topical fluconazole or voriconazole and amphotericin B and topical natamycin that were all ineffective. But the response of posaconazole was significant. After posaconazole, progressive improvement was seen in clinical appearance. BCVA improved to 20/100 in case 1 and 20/40 in case 2. Conclusion. Posaconazole might be an effective treatment option for recalcitrant fusarium keratitis and/or endophthalmitis resistant to conventional antifungal drugs. PMID:25184064

  1. Effectiveness of posaconazole in recalcitrant fungal keratitis resistant to conventional antifungal drugs.

    PubMed

    Altun, A; Kurna, S A; Sengor, T; Altun, G; Olcaysu, O O; Aki, S F; Simsek, M H

    2014-01-01

    Purpose. To present the success of posaconazole in two cases with recalcitrant fugal keratitis that were resistant to conventional antifungal drugs. Method. We presented two cases that were treated with posaconazole after the failure of fluconazole or voriconazole, amphotericin B, and natamycin therapy. Case 1 was a 62-year-old man with a history of ocular trauma. He had been using topical fluorometholone and tobramycin. His best corrected visual acuity (BCVA) was hand motion. He had 5.0 × 4.5?mm area of deep corneal ulcer with stromal infiltration. Case 2 was a 14-year-old contact lens user. He had been using topical moxifloxacin, tobramycin, and cyclopentolate. His BCVA was 20/200. He had a 4.0 × 3.0?mm area of pericentral corneal ulcer with deep corneal stromal infiltration and 2?mm hypopyon. Results. Both patients initially received systemic and topical fluconazole or voriconazole and amphotericin B and topical natamycin that were all ineffective. But the response of posaconazole was significant. After posaconazole, progressive improvement was seen in clinical appearance. BCVA improved to 20/100 in case 1 and 20/40 in case 2. Conclusion. Posaconazole might be an effective treatment option for recalcitrant fusarium keratitis and/or endophthalmitis resistant to conventional antifungal drugs. PMID:25184064

  2. Toxicity of Topical Antifungal Agents to Stratified Human Cultivated Corneal Epithelial Sheets

    PubMed Central

    Kimakura, Mikiko; Yokoo, Seiichi; Nakagawa, Suguru; Yamagami, Satoru; Amano, Shiro

    2014-01-01

    Abstract Purpose: Prolonged use of topical antifungal agents may compromise corneal epithelial integrity. Here, we used an in vitro model of human stratified corneal epithelium to compare the ocular toxicity profiles of 4 different antifungal eye drops. Methods: Human corneal epithelial cell sheets were cultured in a serum-free medium containing 0.1% micafungin, 1% voriconazole, 5% pimaricin, 0.1% amphotericin B, or controls (saline or 5% glucose). Cell viability and barrier function were measured by WST-1 assay and carboxyfluorescein permeability assay, respectively. Cell migration was measured on a wound healing assay. Results: WST-1 assay and carboxyfluorescein permeability assay revealed that amphotericin B was the most toxic drug, followed by pimaricin, micafungin, and voriconazole. Cell migration on a wound healing assay was decreased in the following order, amphotericin B, pimaricin, micafungin, and voriconazole. Conclusions: Topical micafungin and voriconazole appeared to be the least toxic to the corneal epithelium. Drug prescription should consider not only fungal species and susceptibility but also ocular toxicity and stage of treatment. PMID:25280055

  3. Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity.

    PubMed

    Çelebi, Nevin; Ermi?, Seda; Özkan, Semiha

    2015-04-01

    The purpose of this study was to prepare hydrogels and microemulsion (ME)-based gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to evaluate the use of these formulations for the antifungal treatment of fungal infections. Three different hydrogel formulations were prepared using chitosan, Carbopol® 974 and Natrosol® 250 polymers. A pseudo-ternary phase diagram was constructed, and starting from ME formulation, a ME gel form containing 1% Carbopol 974 was prepared. We also examined the characteristic properties of the prepared hyrogels. The physical stability of hydrogels and the ME -based gels were evaluated after storage at different temperatures for a period of 3 months. The release of TER-HCL from the gels and the commercial product (Lamisil®) was carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at 32?°C. The results of the in vitro release study showed that the Natrosol gel released the highest amount of drug, followed by Carbopol gel, chitosan gel, commercial product, and the microoemulsion-based gel in that order. In vitro examination of antifungal activity revealed that all the prepared and commercial products were effective against Candida parapsilosis, Penicillium, Aspergillus niger and Microsporum. These results indicate that the Natrosol®-based hydrogel is a good candidate for the topical delivery of TER-HCL. PMID:24576265

  4. Antifungal activity of lactobacilli and its relationship with 3-phenyllactic acid production.

    PubMed

    Cortés-Zavaleta, O; López-Malo, A; Hernández-Mendoza, A; García, H S

    2014-03-01

    In this study, 13 lactic acid bacteria (LAB) strains (including 5 Lactobacillus casei, 2 Lactobacillus rhamnosus, 2 Lactobacillus fermentum, 1 Lactobacillus acidophilus, 1 Lactobacillus plantarum, 1 Lactobacillus sakei, and 1 Lactobacillus reuteri species) were assessed for both their antifungal activity against four food spoilage molds (Colletotrichum gloeosporioides, Botrytis cinerea, Penicillium expansum, and Aspergillus flavus) and their capability to produce the novel antimicrobial compound 3-phenyllactic acid (PLA). Results demonstrated that all molds were sensitive to varying degrees to the cell-free supernatants (CFS) from LAB fermentations (p<0.05), with growth inhibitions ranging from 2.65% to 66.82%. The inhibition ability of CFS was not affected by a heating treatment (121°C, 20 min); however, it declined markedly when the pH of CFS was adjusted to 6.5. With the exception of L. plantarum NRRL B-4496 and L. acidophilus ATCC-4495, all other LAB strains produced PLA ranging from 0.021 to 0.275 mM. The high minimum inhibitory concentration for commercial PLA (3.01-36.10mM) suggests that it cannot be considered the only compound related with the antifungal potential of studied LAB and that synergistic effects may exist among other metabolism products. PMID:24412414

  5. Antifungal compounds produced by Colletotrichum gloeosporioides, an endophytic fungus from Michelia champaca.

    PubMed

    Chapla, Vanessa Mara; Zeraik, Maria Luiza; Leptokarydis, Ioanis Hcristos; Silva, Geraldo Humberto; Bolzani, Vanderlan Silva; Young, Maria Claudia M; Pfenning, Ludwig Heinrich; Araújo, Angela Regina

    2014-01-01

    In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated phytopathogenic fungi. Chemical investigation of EtOAc extracts of the endophytic fungus Colletotrichum gloeosporioides resulted in the isolation of one new compound, 2-phenylethyl 1H-indol-3-yl-acetate (1), and seven known compounds: uracil (2), cyclo-(S*-Pro-S*-Tyr) (3), cyclo-(S*-Pro-S*-Val) (4), 2(2-aminophenyl)acetic acid (5), 2(4-hydroxyphenyl)acetic acid (6), 4-hydroxy- benzamide (7) and 2(2-hydroxyphenyl)acetic acid (8). All of the compound structures were elucidated using 1D and 2D NMR and MS analyses. The antifungal and AChE inhibitory activities of compounds 1-8 were evaluated in vitro. Compound 1 exhibited promising activity against Cladosporium cladosporioides and C. sphaerospermum that was comparable to that of the positive control nystatin. PMID:25421415

  6. The antifungal activity of Artemisia sieberi essential oil from different localities of Iran against dermatophyte fungi.

    PubMed

    Mahboubi, M; Kazempour, N

    2015-06-01

    Dermatophyte fungi are the most common cause of dermatophytosis in humans and animals. Artemisia sieberi is traditionally used for treatment of fungi related skin infections. In this investigation, we analyzed five samples of A. sieberi oils (different harvesting times and distinctive collecting locations) by GC-FID and GC-MS. The antifungal activities of A. sieberi oils were evaluated against different dermatophytes. The anti-elastase activities of essential oils were also evaluated. The results of analysis showed that the harvesting time and collecting location can affect the chemical compositions and oil yields. The best time for collecting the A. sieberi with high yield was spring season (January-February). There was no significant difference between the desirable anti-dermatophyte activities of A. sieberi oils with different chemical compositions. M. gypseum, T. rubrum and M. canis had more sensitivity than others to A. sieberi oils. The oils with higher amounts of ?-thujone, ?-thujone showed the higher anti-elastase activity. Therefore, A. sieberi can be used as topical antifungal agent for treatment of skin dermatophyte infections. PMID:25770648

  7. In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

    PubMed Central

    Del Poeta, Maurizio; Schell, Wiley A.; Dykstra, Christine C.; Jones, Susan K.; Tidwell, Richard R.; Kumar, Arvind; Boykin, David W.; Perfect, John R.

    1998-01-01

    Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 ?g/ml, and it was the most potent compound against C. neoformans (MIC, ?0.09 ?g/ml). Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents. PMID:9756748

  8. Synthesis and in vitro antifungal efficacy of Cu-chitosan nanoparticles against pathogenic fungi of tomato.

    PubMed

    Saharan, Vinod; Sharma, Garima; Yadav, Meena; Choudhary, Manju Kumari; Sharma, S S; Pal, Ajay; Raliya, Ramesh; Biswas, Pratim

    2015-04-01

    Cu-chitosan nanoparticles were synthesized and evaluated for their growth promotory and antifungal efficacy in tomato (Solanum lycopersicum Mill). Physico-chemical characterization of the developed Cu-chitosan nanoparticles was carried out by DLS, FTIR, TEM, SEM-EDS and AAS. The study highlighted the stability and porous nature of Cu-chitosan nanoparticles. Laboratory synthesized nanoparticles showed substantial growth promotory effect on tomato seed germination, seedling length, fresh and dry weight at 0.08, 0.10 and 0.12% level. At 0.12% concentration these nanoparticles caused 70.5 and 73.5% inhibition of mycelia growth and 61.5 and 83.0% inhibition of spore germination in Alternaria solani and Fusarium oxysporum, respectively, in an in vitro model. In pot experiments, 0.12% concentration of Cu-chitosan nanoparticles was found most effective in percentage efficacy of disease control (PEDC) in tomato plants with the values of 87.7% in early blight and 61.1% in Fusarium wilt. The overall results confirm the significant growth promotory as well as antifungal capabilities of Cu-chitosan nanoparticles. Our model demonstrated the synthesis of Cu-chitosan nanoparticles and open up the possibility to use against fungal disease at field level. Further, developed porous nanomaterials could be exploited for delivery of agrochemicals. PMID:25617841

  9. Requirement for ergosterol in V-ATPase function underlies antifungal activity of azole drugs.

    PubMed

    Zhang, Yong-Qiang; Gamarra, Soledad; Garcia-Effron, Guillermo; Park, Steven; Perlin, David S; Rao, Rajini

    2010-01-01

    Ergosterol is an important constituent of fungal membranes. Azoles inhibit ergosterol biosynthesis, although the cellular basis for their antifungal activity is not understood. We used multiple approaches to demonstrate a critical requirement for ergosterol in vacuolar H(+)-ATPase function, which is known to be essential for fungal virulence. Ergosterol biosynthesis mutants of S. cerevisiae failed to acidify the vacuole and exhibited multiple vma(-) phenotypes. Extraction of ergosterol from vacuolar membranes also inactivated V-ATPase without disrupting membrane association of its subdomains. In both S. cerevisiae and the fungal pathogen C. albicans, fluconazole impaired vacuolar acidification, whereas concomitant ergosterol feeding restored V-ATPase function and cell growth. Furthermore, fluconazole exacerbated cytosolic Ca(2+) and H(+) surges triggered by the antimicrobial agent amiodarone, and impaired Ca(2+) sequestration in purified vacuolar vesicles. These findings provide a mechanistic basis for the synergy between azoles and amiodarone observed in vitro. Moreover, we show the clinical potential of this synergy in treatment of systemic fungal infections using a murine model of Candidiasis. In summary, we demonstrate a new regulatory component in fungal V-ATPase function, a novel role for ergosterol in vacuolar ion homeostasis, a plausible cellular mechanism for azole toxicity in fungi, and preliminary in vivo evidence for synergism between two antifungal agents. New insights into the cellular basis of azole toxicity in fungi may broaden therapeutic regimens for patient populations afflicted with systemic fungal infections. PMID:20532216

  10. Laboratory tests of antifungal agents to treat tadpoles against the pathogen Batrachochytrium dendrobatidis .

    PubMed

    Geiger, Corina C; Schmidt, Benedikt R

    2013-04-11

    The fungus Batrachochytrium dendrobatidis (Bd), which is the etiological agent of the disease chytridiomycosis, is threatening both wild and captive amphibians. While there are some methods of treating amphibians in captivity, no method has yet been shown to be a promising treatment for amphibian populations in natural habitats. Here we present the results of a laboratory experiment in which we tested 2 antifungal agents that might be used to treat amphibians in the field. As a first step towards the goal of developing mitigation methods, we tested the efficiency of these agents in reducing Bd prevalence and loads (zoospore counts) in the laboratory. We exposed naturally infected tadpoles of the midwife toad Alytes obstetricans to different concentrations of the antifungal agents for 7 d. We found that Virkon Aquatic® affected neither Bd prevalence nor loads. At 0.625 ml l-1 of General Tonic®, prevalence was reduced to 60%, and infected animals had greatly reduced burdens. However, tadpole length was reduced by 19% and mass by 32% on average compared to the control group, suggesting a negative effect on fitness. Tadpole survival was not affected at 0.625 ml l-1 or 1.25 ml l-1, but was reduced to 60% at 2.5 ml l-1. Keeping animals in a dilution of General Tonic® for 7 d at a concentration of 0.625 ml l-1 might be an easy way to reduce zoospore counts in large numbers of animals at relatively low cost. PMID:23574705

  11. Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer.

    PubMed

    Griesser, Stefani S; Jasieniak, Marek; Coad, Bryan R; Griesser, Hans J

    2015-01-01

    Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (?20?nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices. PMID:26467660

  12. Antifungal effects of Ellagitannin isolated from leaves of Ocotea odorifera (Lauraceae).

    PubMed

    Yamaguchi, Mirian Ueda; Garcia, Francielle Pelegrin; Cortez, Diógenes Aparício Garcia; Ueda-Nakamura, Tânia; Filho, Benedito Prado Dias; Nakamura, Celso Vataru

    2011-03-01

    Ocotea odorifera is a medicinal plant that is popularly known in Brazil as "canela-sassafrás" and is used to treat dermatosis. This study investigated the antifungal properties of O. odorifera. The methanol extract of O. odorifera was submitted to successive chromatographic separation and yielded Tellimagrandin II (TEL). Candida parapsilosis strain ATCC 22019 was used to determine the minimum inhibitory (MIC) and fungicidal concentrations, and to study the synergistic action with nystatin (NYS), amphotericin (AMP), and fluconazole (FLU). After treatment, the morphology of the yeast was analysed by scanning electron microscopy. Cytotoxicity was assessed in Vero cells, and genotoxicity by the micronucleus test. The TEL structure was proposed based on NMR and comparison with literature data and ESI-MSMS analysis. The compound showed potent inhibitory activity against C. parapsilosis, with a MIC of 1.6 ?M. TEL acted synergistically with NYS, AMP, and FLU, and caused morphological alterations in the yeast cells. The methanolic extract showed low cytotoxicity in vitro and in vivo, and was not mutagenic in mice (P < 0.05). The use of O. odorifera in traditional medicine seems to have a valid basis, in view of the antifungal activity of TEL demonstrated in this study, and may contribute to potential drug development. PMID:20922478

  13. Probiotic Potential of Lactobacillus Strains with Antifungal Activity Isolated from Animal Manure

    PubMed Central

    Ilavenil, Soundharrajan; Park, Hyung Soo; Vijayakumar, Mayakrishnan; Valan Arasu, Mariadhas; Kim, Da Hye; Ravikumar, Sivanesan; Choi, Ki Choon

    2015-01-01

    The aim of the study was to isolate and characterize the lactic acid bacteria (LAB) from animal manure. Among the thirty LAB strains, four strains, namely, KCC-25, KCC-26, KCC-27, and KCC-28, showed good cell growth and antifungal activity and were selected for further characterization. Biochemical and physiology properties of strains confirmed that the strains are related to the Lactobacillus sp.; further, the 16S rRNA sequencing confirmed 99.99% sequence similarity towards Lactobacillus plantarum. The strains exhibited susceptibility against commonly used antibiotics with negative hemolytic property. Strains KCC-25, KCC-26, KCC-27, and KCC-28 showed strong antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Penicillium roqueforti, Botrytis elliptica, and Fusarium oxysporum, respectively. Fermentation studies noted that the strains were able to produce significant amount of lactic, acetic, and succinic acids. Further, the production of extracellular proteolytic and glycolytic enzymes, survival under low pH, bile salts, and gastric juice together with positive bile salt hydrolase (Bsh) activity, cholesterol lowering, cell surface hydrophobicity, and aggregation properties were the strains advantages. Thus, KCC-25, KCC-26, KCC-27, and KCC-28 could have the survival ability in the harsh condition of the digestive system in the gastrointestinal tract. In conclusion, novel L. plantarum KCC-25, KCC-26, KCC-27, and KCC-28 could be considered as potential antimicrobial probiotic strains. PMID:26167534

  14. Lipid and fatty acid profile of the edible fungus Laetiporus sulphurous. Antifungal and antibacterial properties.

    PubMed

    Sinanoglou, Vassilia J; Zoumpoulakis, Panagiotis; Heropoulos, George; Proestos, Charalampos; ?iri?, Ana; Petrovic, Jovana; Glamoclija, Jasmina; Sokovic, Marina

    2015-06-01

    Laetiporus sulphureus is a saprophyte belonging to a specific group of wood-decomposing Basidiomycetes growing on deciduous trees. This fungus has been characterized as a herbal medicine and is also known for its antimicrobial properties. In the present study, high energy extraction techniques using different solvents were compared to obtain maximum yield of the edible fungus Laetiporus sulphureus total lipids. The lipid classes and fatty acid composition of the fruiting bodies' total lipids has been studied using GC-FID and Iatroscan TLC-FID analysis. Among the lipids, the neutral lipids predominated followed by phospholipids and glycolipids. Triglycerides were the most abundant in the neutral lipid fraction, whereas phosphatidylcholine in phospholipids. The existence of relatively high amount of sterols may be correlated to fungus pharmaceutical properties. Total lipids were found to contain high unsaturated degree fatty acids (UFA/SFA>3.4) and dominated of C18:2?-6, C18:1?-9 and C16:0 fatty acids. Antibacterial and antifungal properties of mushrooms' lipid extracts from two different solvents were also examined. Results indicated that hexane extracts possessed better antifungal and slightly better antibacterial activity compared to chloroform extracts though both were less active than the commercial antimicrobial agents. PMID:26028707

  15. In Vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate.

    PubMed

    Hui, Xiaoying; Baker, Stephen J; Wester, Ronald C; Barbadillo, Sherry; Cashmore, Anne K; Sanders, Virginia; Hold, Karin M; Akama, Tsutomu; Zhang, Yong-Kang; Plattner, Jacob J; Maibach, Howard I

    2007-10-01

    Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad-spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690 has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosis. PMID:17621679

  16. Antifungal properties of rhamnolipid produced by Pseudomonas aeruginosa DS9 against Colletotrichum falcatum.

    PubMed

    Goswami, Debahuti; Borah, Siddhartha Narayan; Lahkar, Jiumoni; Handique, Pratap Jyoti; Deka, Suresh

    2015-11-01

    The rhamnolipid biosurfactant (RL-DS9) extracted from the bacterial strain Pseudomonas aeruginosa DS9 was evaluated for its antifungal activity against Colletotrichum falcatum that causes red rot in sugarcane. The surface tension (ST) reduction, biosurfactant production, and antifungal activity of biosurfactant against C. falcatum were investigated by using the medium with different carbon sources and it was found to be maximum in glucose. Moreover, highest reduction of ST and production of biosurfactant was achieved at 4.5% (w/v) concentration of glucose. The efficacy of RL-DS9 was compared with a commercially available rhamnolipid (RL-R95) using microtitre plate assay. Results showed that at 100??g?ml(-1) concentration RL-DS9 exhibited 86.6% inhibition against C. falcatum spore germination, and in the same concentration RL-R95 showed 83.3% inhibition. From liquid chromatography-mass spectrometry (LC-MS) analysis, it was revealed that only two similar congeners Rha-(C10 ) and Rha-Rha-(C10:1 ) were found to be in common among both the rhamnolipids. In the plant bioassay test, it was noted that red rot incidence was reduced on the sugarcane plants treated with RL-DS9. This is the first report that rhamnolipid biosurfactant produced by Pseudomonas aeruginosa DS9 could be able to control red rot disease of sugarcane caused due to the infection with the fungus Colletotrichum falcatum. PMID:26173581

  17. High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery

    PubMed Central

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

    2013-01-01

    ABSTRACT Micro- and nanoscale technologies have radically transformed biological research from genomics to tissue engineering, with the relative exception of microbial cell culture, which is still largely performed in microtiter plates and petri dishes. Here, we present nanoscale culture of the opportunistic fungal pathogen Candida albicans on a microarray platform. The microarray consists of 1,200 individual cultures of 30 nl of C. albicans biofilms (“nano-biofilms”) encapsulated in an inert alginate matrix. We demonstrate that these nano-biofilms are similar to conventional macroscopic biofilms in their morphological, architectural, growth, and phenotypic characteristics. We also demonstrate that the nano-biofilm microarray is a robust and efficient tool for accelerating the drug discovery process: (i) combinatorial screening against a collection of 28 antifungal compounds in the presence of immunosuppressant FK506 (tacrolimus) identified six drugs that showed synergistic antifungal activity, and (ii) screening against the NCI challenge set small-molecule library identified three heretofore-unknown hits. This cell-based microarray platform allows for miniaturization of microbial cell culture and is fully compatible with other high-throughput screening technologies. PMID:23800397

  18. Antifungal activity of nanocapsule suspensions containing tea tree oil on the growth of Trichophyton rubrum.

    PubMed

    Flores, F C; de Lima, J A; Ribeiro, R F; Alves, S H; Rolim, C M B; Beck, R C R; da Silva, Cristiane Bona

    2013-04-01

    The aim of this study was to evaluate, for the first time, the antifungal efficacy of nanocapsules and nanoemulsions containing Melaleuca alternifolia essential oil (tea tree oil) in an onychomycosis model. The antifungal activity of nanostructured formulations was evaluated against Trichophyton rubrum in two different in vitro models of dermatophyte nail infection. First, nail powder was infected with T. rubrum in a 96-well plate and then treated with the formulations. After 7 and 14 days, cell viability was verified. The plate counts for the samples were 2.37, 1.45 and 1.0 log CFU mL(-1) (emulsion, nanoemulsion containing tea tree oil and nanocapsules containing tea tree oil, respectively). A second model employed nails fragments which were infected with the microorganism and treated with the formulations. The diameter of fungal colony was measured. The areas obtained were 2.88 ± 2.08 mm(2), 14.59 ± 2.01 mm(2), 40.98 ± 2.76 mm(2) and 38.72 ± 1.22 mm(2) for the nanocapsules containing tea tree oil, nanoemulsion containing tea tree oil, emulsion and untreated nail, respectively. Nail infection models demonstrated the ability of the formulations to reduce T. rubrum growth, with the inclusion of oil in nanocapsules being most efficient. PMID:23392821

  19. Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests

    PubMed Central

    2014-01-01

    This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5–28 ?g/mL) and Cryptococcus spp. (3–5 ?g/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. PMID:24998949

  20. Sentinel surveillance of invasive candidiasis in Spain: epidemiology and antifungal susceptibility.

    PubMed

    Nieto, M C; Tellería, O; Cisterna, R

    2015-01-01

    In order to know the epidemiology and the changes of antifungal resistance in invasive candidiasis (IC) we carried out this prospective study of Candida strains belonging to patients admitted to 26 Spanish hospitals from June 2011 to June 2012 diagnosed with IC. Clinical information and the identity of the Candida species were collected and antifungal susceptibility was tested using broth microdilution in five agents: amphotericin B, fluconazole, voriconazole, caspofungin and anidulafungin. A total of 705 cases-isolates were documented. Most of the patients suffered from candidemia and several underlying diseases and more than half of them were neutropenic or under immunosuppressive therapy, factors associated with higher mortality. Thirty percent of global mortality was documented. C. albicans was the most frequently isolated species, although an increase of non-C. albicans species was observed. Resistance to fluconazole was of 3.4%, lower than in previous years (6.3%). C. parapsilosis presented a higher MIC90 of echinocandins compared to other species. PMID:25439581

  1. Synergism of antifungal activity between mitochondrial respiration inhibitors and kojic acid.

    PubMed

    Kim, Jong H; Campbell, Bruce C; Chan, Kathleen L; Mahoney, Noreen; Haff, Ronald P

    2013-01-01

    Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H?O?), tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H?O? was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H?O? against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H?O? seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization. PMID:23353126

  2. Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005 from children and adults.

    PubMed

    Gualco, L; Debbia, E A; Bandettini, R; Pescetto, L; Cavallero, A; Ossi, M C; Schito, A M; Marchese, A

    2007-02-01

    The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy. PMID:17175140

  3. Diversity and chemotaxis of soil bacteria with antifungal activity against Fusarium wilt of banana.

    PubMed

    Li, Ping; Ma, Li; Feng, Yun Li; Mo, Ming He; Yang, Fa Xiang; Dai, Hao Fu; Zhao, You Xing

    2012-10-01

    The chemotactic response of bacteria to root exudates plays an important role in the colonization of bacteria in the rhizosphere. In this study, 420 strains of antifungal bacteria against Fusarium oxysporum f. sp. cubense (Foc) were screened for chemotaxis based on a cheA molecular diagnostic method. A total of 124 strains with antifungal efficiencies of 27.26-67.14 % generated a characteristic band of cheA. The chemotaxis of 97 bacterial strains producing a cheA band was confirmed using the drop assay and swarm plate assay using catechol, p-hydroxybenzoic acid, salicylic acid, and asparagine as the attractants. A phylogenetic analysis based on restriction fragment length polymorphisms (RFLPs) and 16S rDNA sequences indicated that the 124 chemotactic antagonists of Foc were affiliated with 18 species of Paenibacillaceae, Bacillaceae, Streptomycineae, Enterobacteriaceae, and Pseudomonadaceae. The chemical composition of banana root exudates were analyzed by GC-MS, and 62 compounds, including alkanes, alkenes, naphthalenes, benzenes, and alcohols, were evaluated. Five representative antagonists of Foc showed 1.76- to 7.75-fold higher chemotactic responses than the control to seven compounds in banana root exudates, as determination by capillary assays. PMID:22763749

  4. Antifungal properties and inhibitory effects upon aflatoxin production of Thymus vulgaris L. by Aspergillus flavus Link.

    PubMed

    Kohiyama, Cássia Yumie; Yamamoto Ribeiro, Milene Mayumi; Mossini, Simone Aparecida Galerani; Bando, Erika; Bomfim, Natália da Silva; Nerilo, Samuel Botiăo; Rocha, Gustavo Henrique Oliveira; Grespan, Renata; Mikcha, Jane Martha Graton; Machinski, Miguel

    2015-04-15

    The antifungal and antiaflatoxigenic properties of Thymus vulgaris essential oil (TEO) were evaluated upon Aspergillus flavus "in vitro". Suspension containing 10(6) of A. flavus were cultivated with TEO in concentrations ranging from 50 to 500 ?g/mL. TEO reached minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 250 ?g/mL. Inhibition of ergosterol biosynthesis was detected at a concentration of 100 ?g/mL of TEO. Morphological evaluation performed by both light microscopy and scanning electron microscopy showed that antifungal activity of TEO could be detected starting at a concentration of 50 ?g/mL and the fungicide effect at a concentration of 250 ?g/mL. TEO completely inhibited production of both B1 and B2 aflatoxins (AFB1 and AFB2) at a concentration of 150 ?g/mL. This way, fungal biomass development and aflatoxin production were dependent on TEO concentration. Therefore, TEO was capable of controlling the growth of A. flavus and its production of aflatoxins. PMID:25466118

  5. Investigations on the Antifungal Effect of Nerol against Aspergillus flavus Causing Food Spoilage

    PubMed Central

    Tian, Jun; Zeng, Xiaobin; Zeng, Hong; Feng, Zhaozhong; Miao, Xiangmin; Peng, Xue

    2013-01-01

    The antifungal efficacy of nerol (NEL) has been proved against Aspergillus flavus by using in vitro and in vivo tests. The mycelial growth of A. flavus was completely inhibited at concentrations of 0.8??L/mL and 0.1??L/mL NEL in the air at contact and vapor conditions, respectively. The NEL also had an evident inhibitory effect on spore germination in A. flavus along with NEL concentration as well as time-dependent kinetic inhibition. The NEL presented noticeable inhibition on dry mycelium weight and synthesis of aflatoxin B1 (AFB1) by A. flavus, totally restraining AFB1 production at 0.6??L/mL. In real food system, the efficacy of the NEL on resistance to decay development in cherry tomatoes was investigated in vivo by exposing inoculated and control fruit groups to NEL vapor at different concentration. NEL vapors at 0.1??L/mL air concentration significantly reduced artificially contaminated A. flavus and a broad spectrum of fungal microbiota. Results obtained from presented study showed that the NEL had a great antifungal activity and could be considered as a benefit and safe tool to control food spoilage. PMID:24453813

  6. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus.

    PubMed

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

    2011-01-01

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

  7. Antifungal Activity of Brazilian Propolis Microparticles against Yeasts Isolated from Vulvovaginal Candidiasis

    PubMed Central

    Dota, Kelen Fátima Dalben; Consolaro, Marcia Edilaine Lopes; Svidzinski, Terezinha Inez Estivalet; Bruschi, Marcos Luciano

    2011-01-01

    Propolis, a resinous compound produced by Apis mellifera L. bees, is known to possess a variety of biological activities and is applied in the therapy of various infectious diseases. The aim of this study was to evaluate the in vitro antifungal activity of propolis ethanol extract (PE) and propolis microparticles (PMs) obtained from a sample of Brazilian propolis against clinical yeast isolates of importance in the vulvovaginal candidiasis (VVC). PE was used to prepare the microparticles. Yeast isolates (n = 89), obtained from vaginal exudates of patients with VVC, were exposed to the PE and the PMs. Moreover, the main antifungal drugs used in the treatment of VVC (Fluconazole, Voriconazole, Itraconazole, Ketoconazole, Miconazole and Amphotericin B) were also tested. Minimum inhibitory concentration (MIC) was determined according to the standard broth microdilution method. Some Candida albicans isolates showed resistance or dose-dependent susceptibility for the azolic drugs and Amphotericin B. Non-C. albicans isolates showed more resistance and dose-dependent susceptibility for the azolic drugs than C. albicans. However, all of them were sensitive or dose-dependent susceptible for Amphotericin B. All yeasts were inhibited by PE and PMs, with small variation, independent of the species of yeast. The overall results provided important information for the potential application of PMs in the therapy of VVC and the possible prevention of the occurrence of new symptomatic episodes. PMID:21607012

  8. Antifungal and Antiproliferative Protein from Cicer arietinum: A Bioactive Compound against Emerging Pathogens

    PubMed Central

    Kumar, Suresh; Kapoor, Vaishali; Gill, Kamaldeep; Singh, Kusum; Xess, Immaculata; Das, Satya N.

    2014-01-01

    The emergence of epidemic fungal pathogenic resistance to current antifungal drugs has increased the interest in developing alternative antibiotics from natural sources. Cicer arietinum is well known for its medicinal properties. The aim of this work was to isolate antimicrobial proteins from Cicer arietinum. An antifungal protein, C-25, was isolated from Cicer arietinum and purified by gel filtration. C-25 protein was tested using agar diffusion method against human pathogenic fungi of ATCC strains and against clinical isolates of Candida krusei, Candida tropicalis, and Candida parapsilosis, and MIC values determined were varied from 1.56 to 12.5??g/mL. The SEM study demonstrated that C-25 induces the bleb-like surface changes, irregular cell surface, and cell wall disruption of the fungi at different time intervals. Cytotoxic activity was studied on oral cancer cells and normal cells. It also inhibits the growth of fungal strains which are resistant to fluconazole. It reduced the cell proliferation of human oral carcinoma cells at the concentration of 37.5??g/mL (IC50) and no toxic effect was found on normal human peripheral blood mononuclear cells even at higher concentration of 600??g/mL. It can be concluded that C-25 can be considered as an effective antimycotic as well as antiproliferative agent against human oral cancer cells. PMID:24963482

  9. Antifungal Activities of Antineoplastic Agents: Saccharomyces cerevisiae as a Model System To Study Drug Action

    PubMed Central

    Cardenas, Maria E.; Cruz, M. Cristina; Del Poeta, Maurizio; Chung, Namjin; Perfect, John R.; Heitman, Joseph

    1999-01-01

    Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to mammalian cells. While this makes it difficult to discover antifungal agents without toxic side effects, it also has enabled detailed studies of drug action in simple genetic model systems. We review here studies on the antifungal actions of antineoplasmic agents. Topics covered include the mechanisms of action of inhibitors of topoisomerases I and II; the immunosuppressants rapamycin, cyclosporin A, and FK506; the phosphatidylinositol 3-kinase inhibitor wortmannin; the angiogenesis inhibitors fumagillin and ovalicin; the HSP90 inhibitor geldanamycin; and agents that inhibit sphingolipid metabolism. In general, these natural products inhibit target proteins conserved from microorganisms to humans. These studies highlight the potential of microorganisms as screening tools to elucidate the mechanisms of action of novel pharmacological agents with unique effects against specific mammalian cell types, including neoplastic cells. In addition, this analysis suggests that antineoplastic agents and derivatives might find novel indications in the treatment of fungal infections, for which few agents are presently available, toxicity remains a serious concern, and drug resistance is emerging. PMID:10515904

  10. Application of Volatile Antifungal Plant Essential Oils for Controlling Pepper Fruit Anthracnose by Colletotrichum gloeosporioides

    PubMed Central

    Hong, Jeum Kyu; Yang, Hye Ji; Jung, Heesoo; Yoon, Dong June; Sang, Mee Kyung; Jeun, Yong-Chull

    2015-01-01

    Anthracnose caused by Colletotrichum gloeosporioides has been destructive during pepper fruit production in outdoor fields in Korea. In vitro antifungal activities of 15 different plant essential oils or its components were evaluated during conidial germination and mycelial growth of C. gloeosporioides. In vitro conidial germination was most drastically inhibited by vapour treatments with carvacrol, cinnamon oil, trans-cinnamaldehyde, citral, p-cymene and linalool. Inhibition of the mycelial growth by indirect vapour treatment with essential oils was also demonstrated compared with untreated control. Carvacrol, cinnamon oil, trans-cinnamaldehyde, citral and eugenol were among the most inhibitory plant essential oils by the indirect antifungal efficacies. Plant protection efficacies of the plant essential oils were demonstrated by reduced lesion diameter on the C. gloeosporioides-inoculated immature green pepper fruits compared to the inoculated control fruits without any plant essential oil treatment. In planta test showed that all plant essential oils tested in this study demonstrated plant protection efficacies against pepper fruit anthracnose with similar levels. Thus, application of different plant essential oils can be used for eco-friendly disease management of anthracnose during pepper fruit production. PMID:26361475

  11. Application of Volatile Antifungal Plant Essential Oils for Controlling Pepper Fruit Anthracnose by Colletotrichum gloeosporioides.

    PubMed

    Hong, Jeum Kyu; Yang, Hye Ji; Jung, Heesoo; Yoon, Dong June; Sang, Mee Kyung; Jeun, Yong-Chull

    2015-09-01

    Anthracnose caused by Colletotrichum gloeosporioides has been destructive during pepper fruit production in outdoor fields in Korea. In vitro antifungal activities of 15 different plant essential oils or its components were evaluated during conidial germination and mycelial growth of C. gloeosporioides. In vitro conidial germination was most drastically inhibited by vapour treatments with carvacrol, cinnamon oil, trans-cinnamaldehyde, citral, p-cymene and linalool. Inhibition of the mycelial growth by indirect vapour treatment with essential oils was also demonstrated compared with untreated control. Carvacrol, cinnamon oil, trans-cinnamaldehyde, citral and eugenol were among the most inhibitory plant essential oils by the indirect antifungal efficacies. Plant protection efficacies of the plant essential oils were demonstrated by reduced lesion diameter on the C. gloeosporioides-inoculated immature green pepper fruits compared to the inoculated control fruits without any plant essential oil treatment. In planta test showed that all plant essential oils tested in this study demonstrated plant protection efficacies against pepper fruit anthracnose with similar levels. Thus, application of different plant essential oils can be used for eco-friendly disease management of anthracnose during pepper fruit production. PMID:26361475

  12. A study on antifungal activity of water-soluble chitosan against Macrophomina phaseolina.

    PubMed

    Chatterjee, Sudipta; Chatterjee, Bishnu P; Guha, Arun K

    2014-06-01

    The objective of this study was to evaluate antifungal effect of water-soluble chitosan (s-chitosan) on Macrophomina phaseolina (M. phaseolina) causing jute seedling infection and monitor the change in activity of released enzymes during infection. The minimum inhibitory concentration (MIC) of s-chitosan for M. phaseolina was found at 12.5g/l and s-chitosan exhibited fungistatic mode of action against this pathogen. The application of s-chitosan (12.5g/l) during infection of jute seedlings by M. phaseolina inhibited fungal infection and length of the seedlings was found almost similar to seedlings without infection. M. phaseolina infected jute seedlings showed length of 22mm over 10 days of incubation and it increased to 58mm in presence of s-chitosan (12.5g/l) during incubation for 10 days. TEM study indicated presence of hyphae in the cortical and epidermal cells of fungus infected jute seedlings indicating colonization by the fungus and it disappeared after treatment with s-chitosan. The changes in enzyme profiles of jute seedling during prevention of fungal infection using s-chitosan helped in proper understanding of mode of action of s-chitosan as antifungal agent. The activity of defense related enzymes like chitosanase and peroxidase in infected seedlings was observed to be enhanced after treatment with s-chitosan. PMID:24747381

  13. The Study of Anticancer and Antifungal Activities of Pistacia integerrima Extract in vitro

    PubMed Central

    Bibi, Y.; Nisa, S.; Zia, M.; Waheed, A.; Ahmed, S.; Chaudhary, M. F.

    2012-01-01

    Pistacia integerrima Stew. ex Brand (Anacardiaceae) is an ethanobotanically important plant species traditionally used in the treatment of chronic wounds, jaundice, dysentery, etc. The crude extract from Pistacia integerrima and its fractions were tested for cytotoxic activity against Michigan Cancer Foundation-7 human breast cancer cell line. We have also investigated that crude stem extract of this plant also exhibits the antitumour as well as antifungal potential activities. Moreover, we have also studied that the crude extract inhibited Michigan Cancer Foundation-7 cell viability in a dose-dependent manner; the poor toxicity (1.6%) at 10 ?g/ml to moderate toxicity (55.4%) at 100 ?g/ml. The IC50 values calculated were 90.9 ?g/ml. The ethyl acetate and chloroform fractions at a concentration of 200 ?g/ml showed ~100 and 97.4% inhibition against Michigan Cancer Foundation-7 cell line, respectively. The crude methanol extract also showed good antitumour (IC50 125 ppm) activity, but weak antifungal activity. These findings reveal that the ethyl acetate and chloroform fractions of Pistacia integerrima are potent cytotoxic fractions, and could be an alternate candidate for the development of novel biologically active compounds. PMID:23626397

  14. Antifungal properties of crude extracts of five Egyptian medicinal plants against dermatophytes and emerging fungi.

    PubMed

    Hashem, Mohamed

    2011-07-01

    Antifungal properties of the crude extracts of five medicinal plants (Artemisia judaica, Ballota undulate, Cleome amblyocarpa, Peganum harmala, and Teucrium polium) were tested against dermatophytes and emerging fungi. Ethanol extract of Ballota undulate was the most effective against all tested fungi. Paecilomyces lilacinus, P. variotii, and Candida albicans were the most sensitive organisms. The minimum inhibitory concentration (MIC) of Ballota undulate ethanol extract against C. albicans, P. lilacinus, and P. variotii was 25 mg/ml. GC-MS analysis revealed that Ballota undulate ethanol extract contains 35 aliphatic and aromatic hydrocarbons, sesquiterpene hydrocarbon along with some other essential oils, which could be involved in antifungal activity. Light microscopy and scanning electron microscopy (SEM) have proved that Ballota undulate ethanol extract exhibits fungicidal effect on P. lilacinus through alterations in hyphal structures including budding of hyphal tip, anomalous structure, such as swelling, decrease in cytoplasmic content, with clear separation of cytoplasm from cell wall in hyphae. SEM clearly showed distorted mycelium, squashed and flattened conidiophores bearing damaged metullae. Eventually, the mycelia became papillated, flattened, and empty. Puncturing and squashing of hyphae as well as complete cell wall disruption were clear signs of complete death of hyphae. PMID:21258865

  15. Metal based new triazoles: Their synthesis, characterization and antibacterial/antifungal activities

    NASA Astrophysics Data System (ADS)

    Sumrra, Sajjad H.; Chohan, Zahid H.

    2012-12-01

    A series of new triazoles and their oxovanadium(IV) complexes have been synthesized, characterized and evaluated for antibacterial/antifungal properties. The new Schiff bases ligands (L1)-(L5) were prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde, 2-acetyl pyridine and 2-methoxy benzaldehyde. The structures of the ligands have been established on the basis of their physical, spectral (IR, 1H and 13C NMR and mass spectrometry) and elemental analytical data. The prepared ligands were used to synthesize their oxovanadium(IV) complexes (1)-(5) which were also characterized by their physical, spectral and analytical data and proposed to have a square pyramidal geometry. The ligands and their complexes were screened for in vitro antibacterial activity against six bacterial species such as, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Bacillus subtilis and for in vitro antifungal activity against six fungal strains, Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glabrata. Cytotoxic nature of the compounds was also reported using brine shrimp bioassay method against Artemia salina.

  16. Adhesion, biofilm formation, cell surface hydrophobicity, and antifungal planktonic susceptibility: relationship among Candida spp.

    PubMed Central

    Silva-Dias, Ana; Miranda, Isabel M.; Branco, Joana; Monteiro-Soares, Matilde; Pina-Vaz, Cidália; Rodrigues, Acácio G.

    2015-01-01

    We have performed the characterization of the adhesion profile, biofilm formation, cell surface hydrophobicity (CSH) and antifungal susceptibility of 184 Candida clinical isolates obtained from different human reservoirs. Adhesion was quantified using a flow cytometric assay and biofilm formation was evaluated using two methodologies: XTT and crystal violet assay. CSH was quantified with the microbial adhesion to hydrocarbons test while planktonic susceptibility was assessed accordingly the CLSI protocol for yeast M27-A3 S4. Yeast cells of non-albicans species exhibit increased ability to adhere and form biofilm. However, the correlation between adhesion and biofilm formation varied according to species and also with the methodology used for biofilm assessment. No association was found between strain's site of isolation or planktonic antifungal susceptibility and adhesion or biofilm formation. Finally CSH seemed to be a good predictor for biofilm formation but not for adhesion. Despite the marked variability registered intra and inter species, C. tropicalis and C. parapsilosis were the species exhibiting high adhesion profile. C. tropicalis, C. guilliermondii, and C. krusei revealed higher biofilm formation values in terms of biomass. C. parapsilosis was the species with lower biofilm metabolic activity. PMID:25814989

  17. Investigations on the antifungal effect of nerol against Aspergillus flavus causing food spoilage.

    PubMed

    Tian, Jun; Zeng, Xiaobin; Zeng, Hong; Feng, Zhaozhong; Miao, Xiangmin; Peng, Xue

    2013-01-01

    The antifungal efficacy of nerol (NEL) has been proved against Aspergillus flavus by using in vitro and in vivo tests. The mycelial growth of A. flavus was completely inhibited at concentrations of 0.8 ? L/mL and 0.1 ? L/mL NEL in the air at contact and vapor conditions, respectively. The NEL also had an evident inhibitory effect on spore germination in A. flavus along with NEL concentration as well as time-dependent kinetic inhibition. The NEL presented noticeable inhibition on dry mycelium weight and synthesis of aflatoxin B1 (AFB1) by A. flavus, totally restraining AFB1 production at 0.6 ? L/mL. In real food system, the efficacy of the NEL on resistance to decay development in cherry tomatoes was investigated in vivo by exposing inoculated and control fruit groups to NEL vapor at different concentration. NEL vapors at 0.1 ? L/mL air concentration significantly reduced artificially contaminated A. flavus and a broad spectrum of fungal microbiota. Results obtained from presented study showed that the NEL had a great antifungal activity and could be considered as a benefit and safe tool to control food spoilage. PMID:24453813

  18. Differential effects of antifungal agents on expression of genes related to formation of Candida albicans biofilms.

    PubMed

    Chatzimoschou, Athanasios; Simitsopoulou, Maria; Antachopoulos, Charalampos; Walsh, Thomas J; Roilides, Emmanuel

    2016-01-01

    The purpose of this study was to analyse specific molecular mechanisms involved in the intrinsic resistance of C. albicans biofilms to antifungals. We investigated the transcriptional profile of three genes (BGL2, SUN41, ECE1) involved in Candida cell wall formation in response to voriconazole or anidulafungin after the production of intermediate and mature biofilms. C. albicans M61, a well-documented biofilm producer strain, was used for the development of intermediate (12 h and 18 h) and completely mature biofilms (48 h). After exposure of cells from each biofilm growth mode to voriconazole (128 and 512 mg l(-1) ) or anidulafungin (0.25 and 1 mg l(-1) ) for 12-24 h, total RNA samples extracted from biofilm cells were analysed by RT-PCR. The voriconazole and anidulafungin biofilm MIC was 512 and 0.5 mg l(-1) respectively. Anidulafungin caused significant up-regulation of SUN41 (3.7-9.3-fold) and BGL2 (2.2-2.8 fold) in intermediately mature biofilms; whereas, voriconazole increased gene expression in completely mature biofilms (SUN41 2.3-fold, BGL2 2.1-fold). Gene expression was primarily down-regulated by voriconazole in intermediately, but not completely mature biofilms. Both antifungals caused down-regulation of ECE1 in intermediately mature biofilms. PMID:26593284

  19. A cultured endophyte community is associated with the plant Clerodendrum inerme and antifungal activity.

    PubMed

    Gong, B; Yao, X H; Zhang, Y Q; Fang, H Y; Pang, T C; Dong, Q L

    2015-01-01

    Fungal endophytes live in the inner tissues of Clerodendrum inerme and may be significant resources for new chemicals in drug discovery. A total of 242 endophytic fungi were recovered from 602 sample segments of C. inerme; 66 were purified. The 66 fungi belonging to 16 taxa and 11 genera (Alternaria, Nigrospora, Bartalinia, Pestalotiopsis, Fusarium, Mycoleptodiscus, Trichoderma, Phomopsis, Diaporthe, Lasiodiplodia, and Curvularia) were identified by morphological characteristics and fungal internal transcribed spacer sequences. The most abundant genera were Alternaria and Lasiodiplodia. Some of the endophytes exhibited tissue specificity. The colonization frequencies of endophytes in the stems were evidently higher than those in the roots and leaves. The crude ethyl acetate extracts were tested against 6 endophytes isolated from C. inerme. Three of 10 (33.3%) endophytes, which were identified as Phomopsis sp, Curvularia sp, and Mycoleptodiscus sp, displayed distinct antifungal activity against ?3 tested fungi. To our knowledge, this is the first report of an endophytic community associated with C. inerme in China and its antifungal activity in vitro. PMID:26125809

  20. Homoisocitrate dehydrogenase from Candida albicans: properties, inhibition, and targeting by an antifungal pro-drug.

    PubMed

    Gabriel, Iwona; Vetter, Natasha D; Palmer, David R J; Milewska, Maria J; Wojciechowski, Marek; Milewski, S?awomir

    2013-03-01

    The LYS12 gene from Candida albicans, coding for homoisocitrate dehydrogenase was cloned and expressed as a His-tagged protein in Escherichia coli. The purified gene product catalyzes the Mg(2+)- and K(+)-dependent oxidative decarboxylation of homoisocitrate to ?-ketoadipate. The recombinant enzyme demonstrates strict specificity for homoisocitrate. SDS-PAGE of CaHIcDH revealed its molecular mass of 42.6 ± 1 kDa, whereas in size-exclusion chromatography, the enzyme eluted in a single peak corresponding to a molecular mass of 158 ± 3 kDa. Native electrophoresis showed that CaHIcDH may exist as a monomer and as a tetramer and the latter form is favored by homoisocitrate binding. CaHIcDH is an hysteretic enzyme. The K(M) values of the purified His-tagged enzyme for NAD(+) and homoisocitrate were 1.09 mM and 73.7 ?M, respectively, and k(cat) was 0.38 s(-1). Kinetic parameters determined for the wild-type CaHIcDH were very similar. The enzyme activity was inhibited by (2R,3S)-3-(p-carboxybenzyl)malate (CBMA), with IC(50) = 3.78 mM. CBMA demonstrated some moderate antifungal activity in minimal media that could be enhanced upon conversion of the enzyme inhibitor into its trimethyl ester derivative (TMCBMA). TMCBMA is the first reported antifungal for which an enzyme of the AAP was identified as a molecular target. PMID:23107040

  1. Antibacterial, Antifungal, and Insecticidal Potentials of Oxalis corniculata and Its Isolated Compounds

    PubMed Central

    Rehman, Azizur; Rehman, Ali; Ahmad, Ijaz

    2015-01-01

    Oxalis corniculata is a common medicinal plant widely used against numerous infectious diseases. The agrochemical potential of methanolic extract, n-hexane, chloroform, ethyl acetate, and n-butanol fractions were assessed to measure the antibacterial, antifungal, and insecticidal activities of the plant. The crude, chloroform, and n-butanol soluble fractions showed excellent activities against Escherichia coli, Shigella dysenteriae, Salmonella typhi, and Bacillus subtilis but have no activity against Staphylococcus aureus. Similarly the crude, n-hexane, and chloroform fractions were also found to have significant activity against fungal strains including Fusarium solani, Aspergillus flexneri, and Aspergillus flavus and have no activity against Aspergillus niger. Chemical pesticides have shown very good results at the beginning, but with the passage of time the need was realized to use the natural plant sources for the safe control of insects. The current study will provide minor contribution towards it. High mortality rate was recorded for the crude extract and chloroform fraction against Tribolium castaneum. The two isolated compounds 5-hydroxy-6,7,8,4?-tetramethoxyflavone (1) and 5,7,4?-trihydroxy-6,8-dimethoxyflavone (2) were evaluated for antibacterial, antifungal, and insecticidal activities. The results showed that compound 2 was more active than compound 1 against the tested bacterial strains and insects. PMID:25873973

  2. Screening of Bunium bulbocastanum for antibacterial, antifungal, phytotoxic and haemagglutination activities.

    PubMed

    Khan, Ibrar; Ahmad, Haroon; Ali, Nasir; Ahmad, Bashir; Tanoli, Hamid

    2013-07-01

    The current study was aimed at screening the Bunium bulbocastanum for its antibacterial, antifungal, phytotoxic and haemagglutination activities.The crude methanolic extract and n-hexane fraction showed significant (89%) and good activity (61%) against Staphylococcus aureus while the CHCl3fraction was moderately active against S.aureus (53%). Moderate activitywas shown by the EtOAc fraction against B. subtilis (44%). This fraction was inactive against P.aerogenosa and S.aureus. The aqueous fraction showed significant activity against B. subtilis (85%), moderate against S.aureus(34 %) and E. coli (33%)and low activity against P.aerogenosa(29%). Our results for antifungal assay indicated that all the test samples were inactive against all the test fungi. The phytotoxic activity of the plant at 1000 and 100 ?g/ml was: crude methanolic extract (53.33 and 46.66%), n-hexane (46.66 and 26.66%), CHCl3 (20 and 6.66%), EtOAc (46.66 and 26.66%) and aqueous (40 and 33.33%). All the test samples (crude methanolic extract and fractions) of B. bulbocastanum were unable to agglutinate RBCs of the human blood indicating that this species lack phytolectins. PMID:23811459

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

    PubMed Central

    Kim, Jane; Marty, Francisco M.; Schwarzinger, Michaël

    2015-01-01

    Background Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. Methods We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran’s Q test, I2 statistic, and between study ?2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Results Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27–0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36–1.87) or overall mortality (RR 0.95, 95% CI 0.46–1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Conclusions Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals. PMID:26554923

  4. Characterization and antifungal activity of gazyumaru (Ficus microcarpa) latex chitinases: both the chitin-binding and the antifungal activities of class I chitinase are reinforced with increasing ionic strength.

    PubMed

    Taira, Toki; Ohdomari, Atsuko; Nakama, Naoya; Shimoji, Makiko; Ishihara, Masanobu

    2005-04-01

    Three chitinases, designated gazyumaru latex chitinase (GLx Chi)-A, -B, and -C, were purified from the latex of gazyumaru (Ficus microcarpa). GLx Chi-A,-B, and -C are an acidic class III (33 kDa, pI 4.0), a basic class I (32 kDa, pI 9.3), and a basic class II chitinase (27 kDa, pI > 10) respectively. GLx Chi-A did not exhibit any antifungal activity. At low ionic strength, GLx Chi-C exhibited strong antifungal activity, to a similar extent as GLx Chi-B. The antifungal activity of GLx Chi-C became weaker with increasing ionic strength, whereas that of GLx Chi-B became slightly stronger. GLx Chi-B and -C bound to the fungal cell-walls at low ionic strength, and then GLx Chi-C was dissociated from them by an escalation of ionic strength, but this was not the case for GLx Chi-B. The chitin-binding activity of GLx Chi-B was enhanced by increasing ionic strength. These results suggest that the chitin-binding domain of basic class I chitinase binds to the chitin in fungal cell walls by hydrophobic interaction and assists the antifungal action of the chitinase. PMID:15849422

  5. In Vitro Activities of Ravuconazole and Four Other Antifungal Agents against Fluconazole-Resistant or -Susceptible Clinical Yeast Isolates

    PubMed Central

    Cuenca-Estrella, Manuel; Gomez-Lopez, Alicia; Mellado, Emilia; Garcia-Effron, Guillermo; Rodriguez-Tudela, Juan L.

    2004-01-01

    The activities of ravuconazole and four other antifungal agents were tested against a collection of 1,796 clinical yeast isolates, including fluconazole-susceptible and -resistant strains. Ravuconazole was active against the majority of fluconazole-resistant isolates; but for 102 of 562 (18%) resistant isolates, mainly Candida tropicalis, Candida glabrata, and Cryptococcus neoformans, ravuconazole MICs were ?1 ?g/ml. PMID:15273127

  6. Rapamycin Antifungal Action Is Mediated via Conserved Complexes with FKBP12 and TOR Kinase Homologs in Cryptococcus neoformans

    PubMed Central

    Cruz, M. Cristina; Cavallo, Lora M.; Görlach, Jenifer M.; Cox, Gary; Perfect, John R.; Cardenas, Maria E.; Heitman, Joseph

    1999-01-01

    Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of antifungal action of the immunosuppressant rapamycin in C. neoformans. In the yeast Saccharomyces cerevisiae and in T cells, rapamycin forms complexes with the FKBP12 prolyl isomerase that block cell cycle progression by inhibiting the TOR kinases. We identified the gene encoding a C. neoformans TOR1 homolog. Using a novel two-hybrid screen for rapamycin-dependent TOR-binding proteins, we identified the C. neoformans FKBP12 homolog, encoded by the FRR1 gene. Disruption of the FKBP12 gene conferred rapamycin and FK506 resistance but had no effect on growth, differentiation, or virulence of C. neoformans. Two spontaneous mutations that confer rapamycin resistance alter conserved residues on TOR1 or FKBP12 that are required for FKBP12-rapamycin-TOR1 interactions or FKBP12 stability. Two other spontaneous mutations result from insertion of novel DNA sequences into the FKBP12 gene. Our observations reveal that the antifungal activities of rapamycin and FK506 are mediated via FKBP12 and TOR homologs and that a high proportion of spontaneous mutants in C. neoformans result from insertion of novel DNA sequences, and they suggest that nonimmunosuppressive rapamycin analogs have potential as antifungal agents. PMID:10330150

  7. Severe Candida albicans panophthalmitis treated with all available and potentially effective antifungal drugs: fluconazole, liposomal amphotericin B, caspofungin, and voriconazole.

    PubMed

    Manfredi, Roberto; Sabbatani, Sergio

    2006-01-01

    A severe case of Candida albicans panophthalmitis, probably prompted by an underlying diabetes mellitus, is reported. The course was prolonged (more than 16 weeks), although favourable after treatment with several antifungal agents, all with a predictable activity in this ocular complication and with proven susceptibility in the present case: fluconazole, liposomal amphotericin B, caspofungin, and voriconazole. PMID:17008248

  8. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens.

    PubMed

    Robbins, Nicole; Spitzer, Michaela; Yu, Tennison; Cerone, Robert P; Averette, Anna K; Bahn, Yong-Sun; Heitman, Joseph; Sheppard, Donald C; Tyers, Mike; Wright, Gerard D

    2015-11-17

    There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ?3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM). Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens. PMID:26549450

  9. Pseudomonas protegens Pf-5 causes discoloration and pitting of mushroom caps due to the production of antifungal metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteria in the diverse P. fluorescens group include mushroom pathogens, such as Pseudomonas tolaasii, and rhizosphere inhabitants known for their antifungal metabolite production and biological control of plant disease, such as Pseudomonas protegens Pf-5. Here, we report that strain Pf-5 causes bro...

  10. Acute and Subacute Oral Toxicity Evaluation of Crude Antifungal Compounds Produced by Lactobacillus plantarum HD1 in Rats

    PubMed Central

    Son, Hee-Kyoung; Chang, Hae-Choon; Lee, Jae-Joon

    2015-01-01

    The aim of this study was to investigate the acute and subacute oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum HD1 in Sprague-Dawley rats. In the acute toxicity study, the crude antifungal compounds (0.625, 1.25, 2.5, and 5.0 g/kg) did not produce mortality, significant changes in general behavior, or changes in the gross appearance of the organs. In the subacute toxicity study, the crude antifungal compounds were administered orally to rats at doses of 0, 0.5, 1.0, and 2.0 g/kg daily for 28 days. There were no test article-related deaths, abnormal clinical signs, or body weight changes. The study also showed no significant differences between the control and treated groups in hematological and serum biochemical parameters, histopathological examination, or any other findings. These results suggest that acute or subacute oral administration of crude antifungal compounds from L. plantarum HD1 is not toxic in rats. PMID:26451356

  11. Species Distribution and In Vitro Antifungal Susceptibility Patterns of 75 Clinical Isolates of Fusarium spp. from Northern Italy?

    PubMed Central

    Tortorano, Anna Maria; Prigitano, Anna; Dho, Giovanna; Esposto, Maria Carmela; Gianni, Claudia; Grancini, Anna; Ossi, Cristina; Viviani, Maria Anna

    2008-01-01

    Fusarium isolates from 75 Italian patients were identified by molecular methods, and their susceptibilities to antifungals were tested in vitro. Fusarium verticillioides was the species most frequently isolated from deep-seated infections, and F. solani was the species most frequently isolated from superficial infections. F. solani isolates showed high azole MICs, while F. verticillioides isolates showed low posaconazole MICs. PMID:18443107

  12. Species distribution and in vitro antifungal susceptibility patterns of 75 clinical isolates of Fusarium spp. from northern Italy.

    PubMed

    Tortorano, Anna Maria; Prigitano, Anna; Dho, Giovanna; Esposto, Maria Carmela; Gianni, Claudia; Grancini, Anna; Ossi, Cristina; Viviani, Maria Anna

    2008-07-01

    Fusarium isolates from 75 Italian patients were identified by molecular methods, and their susceptibilities to antifungals were tested in vitro. Fusarium verticillioides was the species most frequently isolated from deep-seated infections, and F. solani was the species most frequently isolated from superficial infections. F. solani isolates showed high azole MICs, while F. verticillioides isolates showed low posaconazole MICs. PMID:18443107

  13. Non-cytotoxic antifungal agents: isolation and structures of gageopeptides A-D from a Bacillus strain 109GGC020.

    PubMed

    Tareq, Fakir Shahidullah; Lee, Min Ah; Lee, Hyi-Seung; Lee, Yeon-Ju; Lee, Jong Seok; Hasan, Choudhury M; Islam, Md Tofazzal; Shin, Hee Jae

    2014-06-18

    Antifungal resistance and toxicity problems of conventional fungicides highlighted the requirement of search for new safe antifungal agents. To comply with the requirement, we discovered four new non-cytotoxic lipopeptides, gageopeptides A-D, 1-4, from a marine-derived bacterium Bacillus subtilis. The structures and stereochemistry of gageopeptides were determined by NMR data analysis and chemical means. Gageopeptides exhibited significant antifungal activities against pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum with minimum inhibitory concentration (MIC) values of 0.02-0.06 ?M. In addition, these lipopeptides showed significant motility inhibition and lytic activities against zoospores of the late blight pathogen Phytophthora capsici. These compounds also showed potent antimicrobial activity against Gram positive and Gram negative bacteria with MIC values of 0.04-0.08 ?M. However, gageopeptides A-D did not exhibit any cytotoxicity (GI50 > 25 ?M) against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3-4-iodophenyl]-2-(4-nitrophenyl)-2H-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating that these compounds could be promising candidates for the development of non-cytotoxic antifungal agents. PMID:24857413

  14. A carbohydrate-based approach for the total synthesis of 1,3-polyol/alpha-pyrone antifungal natural products.

    PubMed

    Ramana, C V; Srinivas, Burgula; Puranik, Vedavati G; Gurjar, Mukund K

    2005-09-30

    [Chemical reaction: see text] An elimination and stereoselective hydrogenation of alpha-D-glucoheptonic-gamma-lactone derivative has been applied to prepare a differentially protected anti,anti-1,3,5-triol system, the utility of which has been extended for the total synthesis of anti-fungal 1,3-polyol/alpha-pyrone natural products. PMID:16277353

  15. Draft Genome Sequence of Broad-Spectrum Antifungal Bacterium Burkholderia gladioli Strain NGJ1, Isolated from Healthy Rice Seeds

    PubMed Central

    Tyagi, Isha; Kumar, Rajeev; Ghosh, Srayan

    2015-01-01

    We report here the draft genome sequence of Burkholderia gladioli strain NGJ1. The strain was isolated from healthy rice seeds and exhibits broad-spectrum antifungal activity against several agriculturally important pathogens, including Rhizoctonia solani, Magnaporthe oryzae, Venturia inaequalis, and Fusarium oxysporum. PMID:26205861

  16. QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents.

    PubMed

    Medina Marrero, R; Marrero-Ponce, Y; Barigye, S J; Echeverría Díaz, Y; Acevedo-Barrios, R; Casańola-Martín, G M; García Bernal, M; Torrens, F; Pérez-Giménez, F

    2015-11-01

    The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.73% and 92.47%, respectively, for the training set. Additionally, these models are able to correctly classify 92.16% and 87.56% of 706 compounds in an external test set. A comparison of the statistical parameters of the QuBiLs-MAS LDA-based models with those for models reported in the literature reveals comparable to superior performance, although the latter were built over much smaller and less diverse datasets, representing fewer mechanisms of action. It may therefore be inferred that the QuBiLs-MAS method constitutes a valuable tool useful in the design and/or selection of new and broad spectrum agents against life-threatening fungal infections. PMID:26567876

  17. Acute and Subacute Oral Toxicity Evaluation of Crude Antifungal Compounds Produced by Lactobacillus plantarum HD1 in Rats.

    PubMed

    Son, Hee-Kyoung; Chang, Hae-Choon; Lee, Jae-Joon

    2015-09-01

    The aim of this study was to investigate the acute and subacute oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum HD1 in Sprague-Dawley rats. In the acute toxicity study, the crude antifungal compounds (0.625, 1.25, 2.5, and 5.0 g/kg) did not produce mortality, significant changes in general behavior, or changes in the gross appearance of the organs. In the subacute toxicity study, the crude antifungal compounds were administered orally to rats at doses of 0, 0.5, 1.0, and 2.0 g/kg daily for 28 days. There were no test article-related deaths, abnormal clinical signs, or body weight changes. The study also showed no significant differences between the control and treated groups in hematological and serum biochemical parameters, histopathological examination, or any other findings. These results suggest that acute or subacute oral administration of crude antifungal compounds from L. plantarum HD1 is not toxic in rats. PMID:26451356

  18. Dual antifungal properties of cationic antimicrobial peptides polybia-MPI: membrane integrity disruption and inhibition of biofilm formation.

    PubMed

    Wang, Kairong; Yan, Jiexi; Dang, Wen; Xie, Junqiu; Yan, Bo; Yan, Wenjin; Sun, Mengyang; Zhang, Bangzhi; Ma, Mingxia; Zhao, Yanyan; Jia, Fengjing; Zhu, Ranran; Chen, Wei; Wang, Rui

    2014-06-01

    With the increasing emergence of resistant fungi, the discovery and development of novel antifungal therapeutics were urgently needed. Compared with conventional antibiotics, the limited propensity of AMPs to induce resistance in pathogens has attracted great interest. In the present study, the antifungal activity and its mechanism-of-action of polybia-MPI, a cationic peptide from the venom of Social wasp Polybia Paulista was investigated. We demonstrated that polybia-MPI could potently inhibit the growth of Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The 50% inhibitory concentrations (IC50) of Polybia-MPI against cancer cells were much higher than the MICs against the tested C. albicans and C. glabrata cells, indicating that polybia-MPI had high selectivity between the fungal and mammalian cells. Our results also indicated that membrane disturbance mechanism was involved in the antifungal activity. Furthermore, polybia-MPI could inhibit the bio film forming of C. glabrata, which was frequently associated with clinically significant biofilm. These results suggest that polybia-MPI has great advantages in the development of antifungal agents. PMID:24642357

  19. IDENTIFICATION OF ANTIFUNGAL COMPOUNDS IN A BIOLOGICAL CONTROL PRODUCT USING A MICROPLATE INHIBITION BIOASSAY AND MS ANALYSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An inhibition assay was developed to quantify the antifungal activity of a solid state fermentation of Bacillus subtilis. Methanol extracts were tested against a spore solution of the fungal pathogen Fusarium oxysporum f. sp. melonis using a 96-well microplate bioassay. HPLC analysis of extracts s...

  20. Mechanism of Antifungal Activity of Terpenoid Phenols Resembles Calcium Stress3 and Inhibition of the TOR Pathway4

    E-print Network

    Rao, Rajini

    1 1 2 Mechanism of Antifungal Activity of Terpenoid Phenols Resembles Calcium Stress3 October 2010 #12;2 ABSTRACT1 Terpenoid phenols, including carvacrol, are components of plant essential response to terpenoid phenols, we used Saccharomyces cerevisiae as5 a model organism and monitored temporal