Science.gov

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. 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...

  4. 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...

  5. 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

  6. 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...

  7. 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...

  8. Inhibition of rat and human steroidogenesis by triazole antifungals.

    PubMed

    Goetz, Amber K; Rockett, John C; Ren, Hongzu; Thillainadarajah, Inthirany; Dix, David J

    2009-12-01

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles that are known to modulate expression of cytochrome P450 (CYP) genes and enzymatic activities were tested for effects on steroidogenesis using rat in vivo (triadimefon), rat in vitro (myclobutanil and triadimefon), and human in vitro (myclobutanil, propiconazole, and triadimefon) model systems. Hormone production was measured in testis organ cultures from untreated adult and neonatal rats, following in vitro exposure to 1, 10, or 100 muM of myclobutanil or triadimefon. Myclobutanil and triadimefon reduced media levels of testosterone by 40-68% in the adult and neonatal testis culture, and altered steroid production in a manner that indicated CYP17-hydroxylase/17,20 lyase (CYP17A1) inhibition at the highest concentration tested. Rat to human comparison was explored using the H295R (human adrenal adenocarcinoma) cell line. Following 48 h exposure to myclobutanil, propiconazole, or triadimefon at 1, 3, 10, 30, or 100 muM, there was an overall decrease in estradiol, progesterone, and testosterone by all three triazoles. These data indicate that myclobutanil, propiconazole, and triadimefon are weak inhibitors of testosterone production in vitro. However, in vivo exposure of rats to triazoles resulted in increased serum and intra-testicular testosterone levels. This discordance could be due to higher concentrations of triazoles tested in vitro, and differences within an in vitro model system lacking hepatic metabolism and neuroendocrine control. PMID:19938956

  9. METABOLISM OF MYCLOBUTANIL AND TRIADIMEFON BY HUMAN AND RAT CYTOCHROME P450 ENZYMES AND LIVER MICROSOMES.

    EPA Science Inventory

    Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil wa...

  10. 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...

  11. 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...

  12. Stereoselective degradation of chiral fungicide myclobutanil in rat liver microsomes.

    PubMed

    Yan, Jin; Zhang, Ping; Wang, Xinru; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao

    2014-01-01

    Myclobutanil, (RS)-2-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-ylmethyl)hexanenitrile is a broad-spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high-performance liquid chromatography (HPLC) with a cellulose-tris-(3,5-dimethyl-phenylcarbamate)-based chiral stationary phase (CDMPC-CSP) under reversed phase condition. The t(1/2) of (+)-myclobutanil is 8.49 min, while the t(1/2) of (-)-myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)-myclobutanil was much faster than (-)-myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The V(max) of (+)-myclobutanil was about 4-fold of (-)-myclobutanil and the CL(int) of (+)-myclobutanil was three times as much as (-)-myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health. PMID:24249205

  13. 77 FR 75039 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... propiconazole in food as follows: i. Acute exposure. Quantitative acute dietary exposure and risk assessments... whether quantitative cancer exposure and risk assessments are appropriate for a food-use pesticide based... level water exposure models in the dietary exposure analysis and risk assessment for propiconazole...

  14. 76 FR 27261 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ...This regulation establishes tolerances for residues of propiconazole in or on multiple commodities which are identified and discussed later in this document. Interregional Research Project 4 (IR-4) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA). In addition, this action establishes a time-limited tolerance for residues of propiconazole in or on......

  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. 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...

  17. 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...

  18. 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 (...

  19. 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...

  20. 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.

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

    PubMed

    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. PMID:19409404

  2. 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...

  3. Enantioselectivity in tebuconazole and myclobutanil non-target toxicity and degradation in soils.

    PubMed

    Li, Yuanbo; Dong, Fengshou; Liu, Xingang; Xu, Jun; Han, Yongtao; Zheng, Yongquan

    2015-03-01

    Tebuconazole and myclobutanil are two widely used triazole fungicides, both comprising two enantiomers with different fungicidal activity. However, their non-target toxicity and environmental behavior with respect to enantioselectivity have received limited attention. In the present study, tebuconazole and myclobutanil enantiomers were isolated and used to evaluate the occurrence of enantioselectivity in their acute toxicity to three non-target organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Significant differences were found: R-(-)-tebuconazole was about 1.4-5.9 times more toxic than S-(+)-tebuconazole; rac-myclobutanil was about 1.3-6.1 and 1.4-7.3 more toxic than (-)-myclobutanil and (+)-myclobutanil, respectively. Enantioselectivity was further investigated in terms of fungicide degradation in seven soil samples, which were selected to cover a broad range of soil properties. In aerobic or anaerobic soils, the S-(+)-tebuconazole degraded faster than R-(-)-tebuconazole, and the enantioselectivity showed a correlation with soil organic carbon content. (+)-Myclobutanil was preferentially degraded than (-)-myclobutanil in aerobic soils, whereas both enantiomers degraded at similar rates in anaerobic soils. Apparent correlations of enantioselectivity with soil pH and soil texture were observed for myclobutanil under aerobic conditions. In addition, both fungicides were configurationally stable in soils, i.e., no enantiomerization was found. Enantioselectivity may be a common phenomenon in both aquatic toxicity and biodegradation of chiral triazole fungicides, and this should be considered when assessing ecotoxicological risks of these compounds in the environment. PMID:25475972

  4. 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.

  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 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), NO(-)3-N and NH(+)4-N 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, NH(+)4-N, and gene abundance of total bacteria, fungi, N2-fixing bacteria, AOA, and AOB, with the exception of a brief increase in NO(-)3-N 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 NH(+)4-N concentration were not significantly affected by myclobutanil. The RB and MBN were decreased transitorily in the T10 treatment. The NO(-)3-N 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

  7. 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

  8. Acute toxicity, bioactivity, and enantioselective behavior with tissue distribution in rabbits of myclobutanil enantiomers.

    PubMed

    Sun, Mingjing; Liu, Donghui; Qiu, Xinxu; Zhou, Qian; Shen, Zhigang; Wang, Peng; Zhou, Zhiqiang

    2014-12-01

    The enantioselective bioactivity against pathogens (Cercospora arachidicola, Fulvia fulva, and Phytophthora infestans) and acute toxicity to Daphnia magna of the fungicide myclobutanil enantiomers were studied. The (+)-enantiomer in an antimicrobial activity test was about 1.79-1.96 times more active than the (-)-enantiomer. In the toxicity assay, the calculated 24-h LC50 values of the (-)-form, rac-form and (+)-form were 16.88, 13.17, and 11.91 mg/L, and the 48-h LC50 values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)-myclobutanil was more toxic. Meanwhile, the enantioselective metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)-enantiomer was 1.68-fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)-enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low-activity (-)-myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. PMID:25043148

  9. 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 μ/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.

  10. MYCLOBUTANIL AND TRIADIMEFON METHABOLISM BY RAT CYP ISOFORMS AND LIVER MICROSOMES

    EPA Science Inventory


    The mode of action of conazole fungicides is to inhibit cytochrome P450 (CYP) 51 activity and thus the biosynthesis of ergosterol by fungi. Conazoles can also modulate other CYP activities in vertebrate species including humans. Myclobutanil (MCL) and triadimefon (TRD) are ag...

  11. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J.; Ellanskaya, Irina; Ellanskaya, legal representative, Natalia; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K.; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    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.

  12. 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...

  13. Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI–MS and preliminary pharmacological studies

    PubMed Central

    Marangoci, Narcisa; Mares, Mihai; Silion, Mihaela; Fifere, Adrian; Varganici, Cristian; Nicolescu, Alina; Deleanu, Calin; Coroaba, Adina; Pinteala, Mariana; Simionescu, Bogdan C.

    2011-01-01

    A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI–MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds (1J(HC)3=207 Hz, 1J(CH)5=214 Hz, for PCZ; 1J(HC)3=208 Hz and 1J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI–MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents. PMID:25755979

  14. 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 ...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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 ...

  1. In vitro and in vivo evidence for the inhibition of brassinosteroid synthesis by propiconazole through interference with side chain hydroxylation.

    PubMed

    Oh, Keimei; Matsumoto, Tadashi; Hoshi, Tomoki; Yoshizawa, Yuko

    2016-05-01

    We carried out the biochemical evaluation of the target site of propiconazole in BR biosynthesis. Applying BR biosynthesis intermediates to Arabidopsis seedlings grown in the presence of propiconazole under dark condition, we found that the target site of propiconazole in BR biosynthesis can be identified among the C22 and C23 side chain hydroxylation steps from campestanol to teasterone. Using differential spectra techniques to determine the binding affinity of propiconazole to CYP90D1, which is responsible for C23 hydroxylation of BR, we found that propiconazole induced typical type II binding spectra in response to purified recombinant CYP90D1 and the Kd value was found approximately 0.76 μM. PMID:26987039

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

    PubMed

    Skolness, Sarah Y; Blanksma, Chad A; Cavallin, Jenna E; Churchill, Jessica J; Durhan, Elizabeth J; Jensen, Kathleen M; Johnson, Rodney D; Kahl, Michael D; Makynen, Elizabeth A; Villeneuve, Daniel L; Ankley, Gerald T

    2013-04-01

    Conazoles are designed to inhibit cytochrome P450 (CYP) 14α-demethylase, an enzyme key to fungal cell wall formation. In vertebrates, conazoles may inhibit other CYPs, potentially disrupting processes like sex steroid synthesis. Propiconazole is a current-use pesticide that is among the first chemicals being tested in the U.S. Environmental Protection Agency endocrine disruptor screening program. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, or 1000 µg propiconazole/l in a 21-day study that evaluated apical reproductive endpoints (fecundity, fertility, hatch); measures of endocrine function and steroid synthesis, such as cholesterol, vitellogenin (VTG), and sex steroid (testosterone [T], 17β-estradiol [E2]) concentrations in the plasma; and changes in gonadal expression of steroidogenic genes. Plasma E2 and VTG concentrations in females were reduced by exposure to propiconazole, and egg production was decreased in the 500 and 1000 µg/l treatment groups. These in vivo effects coincided with inhibition of E2 synthesis by ovary explants exposed to propiconazole in vitro. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and upregulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroidogenic acute regulatory protein. Other than an increase in relative testis weight, effects on endocrine function in males were less pronounced than in females. This study provides important data relative to the potential endocrine activity of propiconazole in fish and, more generally, to the further delineation of pathways for the reproductive effects of steroid synthesis inhibitors in fish. PMID:23339182

  3. [Determination of myclobutanil 25% WG degradation dynamics in ginseng root, stem, leaf and soil by HPLC-MS/MS].

    PubMed

    Wang, Yan; Wang, Chun-Wei; Gao, Jie; Cui, Li-Li; Xu, Yun-Cheng

    2014-07-01

    A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days. PMID:25276964

  4. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

    PubMed

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-07-30

    Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment. PMID:24962053

  5. The oxidative stress response of myclobutanil and cyproconazole on Tetrahymena thermophila.

    PubMed

    Huang, Ai-Guo; Tu, Xiao; Liu, Lei; Wang, Gao-Xue; Ling, Fei

    2016-01-01

    Using Tetrahymena thermophila as experimental models, the oxidative stress of triazole fungicides myclobutanil (MYC) and cyproconazole (CYP) was investigated. Results showed that 24-h EC50 values for MYC and CYP were 16.67 (13.37-19.65) and 20.44 (18.85-21.96) mg/L, respectively; 48-h EC50 values for MYC and CYP were 14.31 (13.13-15.42) and 18.76 (17.09-20.31) mg/L, respectively. Reactive oxygen species was significantly induced and cytotoxicity was caused by MYC and CYP by increasing propidium iodide (PI) fluorescence. Damage of regular wrinkles and appearing of small holes on the cell surface were observed by SEM. Furthermore, MYC and CYP also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that MYC and CYP lead to oxidative stress on T. thermophila. The information presented in this study will provide insights into the mechanism of triazoles-induced oxidative stress on T. thermophila. PMID:26724607

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. What causes the difference in synergistic potentials of propiconazole and prochloraz toward pyrethroids in Daphnia magna?

    PubMed

    Dalhoff, Kristoffer; Gottardi, Michele; Kretschmann, Andreas; Cedergreen, Nina

    2016-03-01

    Azole fungicides (imidazoles and triazoles) are known to function synergistically with several compounds, especially with pyrethroid insecticides, most likely by inhibiting cytochrome P450. Different azole fungicides have been shown to differ in their synergistic potentials usually with the imidazoles being stronger synergists than the triazoles. This study investigated whether the toxicokinetic and toxicodynamic (TKTD) properties of the imidazole prochloraz and triazole propiconazole can explain their different synergistic potential toward the freshwater macroinvertebrate Daphnia magna. Pulse exposure to external concentrations of propiconazole (1.4μM) and prochloraz (1.7μM) for 18h resulted in internal concentrations of 22.7 and 53.5μmolkg(-1)w.w. for propiconazole and prochloraz, respectively. This 2-fold difference in bioaccumulation corresponded very well with the observed 2.7-fold lower external EC50-estimate (7 days) for prochloraz compared to propiconazole. The estimated IC50 for the in vivo inhibition of cytochrome P450 (ECOD) activity, however, measured as transformation of 7-ethoxycoumarin into 7-hydroxycoumarin, was almost 500-fold higher for prochloraz (IC50: 0.011±0.002μM) compared to propiconazole (IC50: 4.9±0.06μM). When indirectly measuring the binding strength of the two azoles, daphnids exposed to propiconazole recovered roughly 80% of their ECOD activity compared to the control shortly after being moved to azole-free medium, indicating that propiconazole causes reversible inhibition of cytochrome P450. In contrast, the ECOD-activity remained inhibited in the prochloraz-exposed daphnids for 12h following transfer to azole-free medium, which correlated with elimination of the measured internal prochloraz concentration (DT95≈13h). These results indicate that lethal toxicity of the azole fungicides is mainly driven by toxicokinetics through their hydrophobicities resulting in different internal concentrations. Their synergistic potential toward pyrethroid toxicity, on the other hand, is mainly governed by their toxicodynamic effects measured as the differences in IC50-values toward in vivo cytochrome P450 (ECOD) activity together with the proposed binding strength measured indirectly through the recovery of ECOD activity as a function of internal azole concentrations. PMID:26784738

  11. Development and application of quantitative methods for monitoring dermal and inhalation exposure to propiconazole.

    PubMed

    Flack, Sheila; Goktepe, Ipek; Ball, Louise M; Nylander-French, Leena A

    2008-03-01

    Quantitative methods to measure dermal and inhalation exposure to the fungicide propiconazole were developed in the laboratory and applied in the occupational exposure setting for monitoring five farm workers' exposure during pesticide preparation and application to peach crops. Dermal exposure was measured with tape-strips applied to the skin, and the amount of propiconazole was normalized to keratin content in the tape-strip. Inhalation exposure was measured with an OVS tube placed in the worker's breathing-zone during pesticide handling. Samples were analyzed by GC-MS in EI+ mode (limit of detection 6 pg microl(-1)). Dermal exposure ranged from non-detectable to 32.1 +/- 22.6 ng per microg keratin while breathing-zone concentrations varied from 0.2 to 2.2 microg m(-3). A positive correlation was observed between breathing-zone concentrations and ambient air temperature (r2 = 0.87, p < 0.01). Breathing-zone concentrations did not correlate with dermal exposure levels (r2 = 0.11, p = 0.52). Propiconazole levels were below limit of detection when rubber gloves, coveralls, and full-face mask were used. The total-body propiconazole dose, determined for each worker by summing the estimated dermal dose and inhalation dose, ranged from 0.01 to 12 microg per kg body weight per day. Our results show that tape-stripping of the skin and the OVS can be effectively utilized to measure dermal and inhalation exposure to propiconazole, respectively, and that the dermal route of exposure contributed substantially more to the total dose than the inhalation route. PMID:18392276

  12. Enantioselective analysis of triazole fungicide myclobutanil in cucumber and soil under different application modes by chiral liquid chromatography/tandem mass spectrometry.

    PubMed

    Dong, Fengshou; Cheng, Li; Liu, Xingang; Xu, Jun; Li, Jing; Li, Yuanbo; Kong, Zhiqiang; Jian, Qiu; Zheng, Yongquan

    2012-02-29

    A sensitive and enantioselective method was developed and validated for the determination of myclobutanil enantiomers by chiral liquid chromatography coupled with tandem mass spectrometry. The separation and determination were performed using reversed-phase chromatography on a Chiralcel OD-RH column, with ACN-water (70/30, v/v) as the mobile phase under isocratic conditions at 0.5 mL/min flow rate. The matrix effect, linearity, precision, accuracy, and stability were evaluated. The proposed method then was successfully applied to the study of enantioselective degradation of rac-myclobutanil in cucumber and soil under different application modes. The results showed that the preferential degradation of (+)-myclobutanil resulted in an enrichment of the (-)-myclobutanil residue in plant and soil. Moreover, in cucumber, the stereoselective intensity of myclobutanil under root douche treatment was stronger than that under foliar spraying treatment, whereas in soil, the intensity was exactly opposite. The probable reasons underlying these enantioselective effects were also discussed. This study highlighted the importance of examining the fate of both enantiomers in the greenhouse system for the correct use of chiral pesticides. PMID:22288843

  13. 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 ...

  14. Dynamics of difenoconazole and propiconazole residues on pomegranate over 2 years under field conditions.

    PubMed

    Mohapatra, Soudamini

    2016-03-01

    Residue dynamics of difenoconazole and propiconazole on pomegranate was studied after application at the recommended and double doses of 125 and 250 g active ingredient (a.i.) ha(-1) during August-October 2012. The study was repeated during the same period in 2013. QuEChERS method, in conjunction with gas chromatography (GC), was used for analysis of the fungicides after carrying out the method validation. The recoveries of the fungicides from pomegranate and soil were between 80.3 and 96.2 %; the limit of detection (LOD) and limit of quantification (LOQ) were 0.016 and 0.05 mg kg(-1), respectively. The uncertainties of measurement were between 9.7 and 16.3 %. The initial residue deposits of difenoconazole were 0.875 and 1.205 mg kg(-1) from treatment at the recommended dose and 1.54 and 1.672 mg kg(-1) from treatment at the double dose from the first- and second-year studies. Propiconazole residues were 0.663 and 0.864 mg kg(-1) from recommended dose treatments and 1.474 and 2.045 mg kg(-1) from double dose treatments from the first- and second-year studies. The half-lives of degradation of difenoconazole were 6.4-8.4 days and propiconazole 7.9-8.5 days over the 2 years. Residues of difenoconazole and propiconazole remained on the pomegranate fruit surface and did not move to the edible part (aril). The pre-harvest intervals (PHIs), the time required for the residues to reduce below their respective EU maximum residue limits (MRLs), were 25.4 and 30.8 days for difenoconazole and 33.3 and 43.8 days for propiconazole from treatments at the recommended and double doses, respectively. Keeping in view consumer safety, the longer PHI from the two studies has been selected. PMID:26590055

  15. 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...

  16. 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 ...

  17. Fate and transport of agriculturally applied fungicidal compounds, azoxystrobin and propiconazole.

    PubMed

    Edwards, Paul G; Murphy, Tracye M; Lydy, Michael J

    2016-03-01

    Fungicidal active ingredients azoxystrobin and propiconazole, individually and in combination, have been marketed worldwide in a range of fungicide treatment products for preventative and curative purposes, respectively. Their presence in streams located throughout the midwestern and southeastern United States warrant the need for research into the potential routes of transport of these fungicides in an agricultural field setting. Potential canopy penetration and drift effects of these fungicides during aerial and ground applications were studied in the current project. Canopy penetration was observed for both application types, however drift was associated only with the aerial application of these fungicides. Azoxystrobin and propiconazole persisted in the soil up to 301 d, with peak concentrations occurring approximately 30 d after application. The predominant mode of transport for these compounds was agricultural runoff water, with the majority of the fungicidal active ingredients leaving the target area during the first rain event following application. The timing of application in relation to the first rain event significantly affected the amount of loss that occurred, implying application practices should follow manufacturer recommended guidelines. PMID:26741551

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal manure-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) at 300, 450 and 600 degrees Celsius (denoted as BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 ...

  19. 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.

  20. 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

  1. Overcoming antifungal resistance.

    PubMed

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

    2014-03-01

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

  2. Overcoming antifungal resistance

    PubMed Central

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

    2014-01-01

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

  3. Triazole antifungals: a review.

    PubMed

    Peyton, L R; Gallagher, S; Hashemzadeh, M

    2015-12-01

    Invasive fungal infections and systemic mycosis, whether from nosocomial infection or immunodeficiency, have been on an upward trend for numerous years. Despite advancements in antifungal medication, treatment in certain patients can still be difficult for reasons such as impaired organ function, limited administration routes or poor safety profiles of the available antifungal medications. The growing number of invasive fungal species becoming resistant to current antifungal medications is of appreciable concern. Triazole compounds containing one or more 1,2,4-triazole rings have been shown to contain some of the most potent antifungal properties. Itracon-azole and fluconazole were some of the first triazoles synthesized, but had limitations associated with their use. Second-generation triazoles such as voriconazole, posa-conazole, albaconazole, efinaconazole, ravuconazole and isavuconazole are all derivatives of either itraconazole or fluconazole, and designed to overcome the deficiencies of their parent drugs. The goal of this manuscript is to review antifungal agents derived from triazole. PMID:26798851

  4. Impact of Fungicides Chlorothalonil and Propiconazole on Microbial Activities in Groundnut (Arachis hypogaea L.) Soils.

    PubMed

    Ramudu, A C; Mohiddin, G Jaffer; Srinivasulu, M; Madakka, M; Rangaswamy, V

    2011-01-01

    Introduction of agrochemicals (fungicides) into soil may have lasting effects on soil microbial activities and thus affect soil health. In order to determine the changes in microbial activity in a black clay and red sandy loam soils of groundnut (Arachis hypogaea L.) cultivated fields, a case study was conducted with propiconazole and chlorothalonil to evaluate its effects on soil enzymes (cellulase and invertase) throughout 40 days of incubation under laboratory conditions with different concentrations (1.0, 2.5, 5.0, 7.5, and 10.0 kg ha(-1)). Individual application of the two fungicides at 1.0, 2.5, and 5.0 kg ha(-1) to the soil distinctly enhanced the activities of cellulase and invertase but at higher concentrations of 7.5 and 10 kg ha(-1) was toxic or innocuous to both cellulase and invertase activities. In soil samples receiving 2.5-5.0 kg ha(-1) of the fungicides, the accumulation of reducing sugar was pronounced more at 20 days, and the activity of the cellulase and invertase was drastically decreased with increasing period of incubation up to 30 and 40 days. PMID:23724306

  5. Multiple biomarkers responses in juvenile rainbow trout, Oncorhynchus mykiss, after acute exposure to a fungicide propiconazole.

    PubMed

    Li, Zhi-Hua; Zlabek, Vladimir; Velisek, Josef; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2013-03-01

    In this study, the toxic effects of propiconazole (PCZ), a triazole fungicide present in aquatic environment, were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute toxicity test with the concentration of 5.04 mg/L (96 h LC50). Morphological indices, hematological parameters, liver xenobiotic-metabolizing response, and tissue antioxidant status were evaluated. Compared with the control group, fish exposed to PCZ showed significantly higher Leuko, PCV, MCHC, and hepatic EROD, and significantly lower MCV. CF and HSI were not significantly different among groups. SOD, CAT, GPx, and GR activities increased significantly in liver of experimental groups, but decreased significantly in gill. In general, antioxidant enzyme activity in intestine was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill. Additionally, through chemometrics of all parameters measured in this study, two groups with 67.29% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in different tissues of fish indicated that PCZ-induced the stressful environmental conditions. But according to PCZ residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013. PMID:21384499

  6. Impact of Fungicides Chlorothalonil and Propiconazole on Microbial Activities in Groundnut (Arachis hypogaea L.) Soils

    PubMed Central

    Ramudu, A. C.; Mohiddin, G. Jaffer; Srinivasulu, M.; Madakka, M.; Rangaswamy, V.

    2011-01-01

    Introduction of agrochemicals (fungicides) into soil may have lasting effects on soil microbial activities and thus affect soil health. In order to determine the changes in microbial activity in a black clay and red sandy loam soils of groundnut (Arachis hypogaea L.) cultivated fields, a case study was conducted with propiconazole and chlorothalonil to evaluate its effects on soil enzymes (cellulase and invertase) throughout 40 days of incubation under laboratory conditions with different concentrations (1.0, 2.5, 5.0, 7.5, and 10.0 kg ha−1). Individual application of the two fungicides at 1.0, 2.5, and 5.0 kg ha−1 to the soil distinctly enhanced the activities of cellulase and invertase but at higher concentrations of 7.5 and 10 kg ha−1 was toxic or innocuous to both cellulase and invertase activities. In soil samples receiving 2.5–5.0 kg ha−1 of the fungicides, the accumulation of reducing sugar was pronounced more at 20 days, and the activity of the cellulase and invertase was drastically decreased with increasing period of incubation up to 30 and 40 days. PMID:23724306

  7. Antifungal compounds from cyanobacteria.

    PubMed

    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

    2015-04-01

    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. 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

  9. 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...

  10. 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

  11. 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 ...

  12. 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 ...

  13. Antifungal susceptibility testing.

    PubMed Central

    Rex, J H; Pfaller, M A; Rinaldi, M G; Polak, A; Galgiani, J N

    1993-01-01

    Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work. PMID:8269392

  14. Antifungal lock therapy.

    PubMed

    Walraven, Carla J; Lee, Samuel A

    2013-01-01

    The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT. PMID:23070153

  15. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

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

    PubMed

    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 α,β-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

  17. 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 α,β-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

  18. Antifungal activity of Apulia region propolis.

    PubMed

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

    1999-12-01

    A study was carried out to assess the in vitro antifungal activity of some natural Apulian propolis extracts of different origin. Their antifungal activity was compared to the antifungal activity of conifers and commercial propolis extracts. All extracts revealed antifungal activity against dermatophytes and Candida species. The antifungal activity differences found depended on the origin of the propolis and the solvent used for extraction. The best antifungal activity was given by the 'Orimini' propolis. The antifungal activity may have been influenced by the presence of different cinnamic and flavonoid components and their different concentration in the extracts. Further investigations are needed to validate this hypothesis. PMID:10870567

  19. Differential sensitivity of barley (Hordeum vulgare L.) to chlorpyrifos and propiconazole: Morphology, cytogenetic assay and photosynthetic pigments.

    PubMed

    Dubey, Pragyan; Mishra, Amit Kumar; Shukla, Pratiksha; Singh, Ashok Kumar

    2015-10-01

    The present investigation was performed to evaluate the effects of an insecticide and fungicide, namely, chlorpyrifos (CP) and propiconazole (PZ) on barley (Hordeum vulgare L. variety Karan-16). The seeds were treated with three concentrations of CP and PZ, i.e., 0.05%, 0.1% and 0.5% for 6 hours after different pre-soaking durations of 7, 17 and 27 hours. Different pre-soaking durations (7, 17 and 27 h) represent three phases of the cell cycle i.e., G1, S and G2, respectively. Double distilled water and ethyl methane sulfonate were used as negative and positive controls, respectively. As compared to their respective controls, treated root tip meristematic cells of barley showed significant reductions in the germination percentage, seedling height, mitotic index and comparative increase in chromosomal aberrations against both the pesticides, and the magnitude was higher in CP. After treatment with the pesticides, chlorophyll and carotenoid contents increased up to 0.1% but reduced at 0.5% and the decrease was more prominent in CP as compared to PZ. In treated cells, fragmentation, stickiness, bridges, multipolar anaphase and diagonal anaphase were observed as aberrations. As compared to control, chromosomal aberrations were higher in CP as compared to PZ. The results of the present study concluded that CP induced chromosomal aberrations were more frequent than PZ; hence it has higher probability to cause genotoxicity in barley. PMID:26453227

  20. CNS pharmacokinetics of antifungal agents.

    PubMed

    Kethireddy, Shravan; Andes, David

    2007-08-01

    The goal in treatment of infections is to achieve a beneficial effect while minimizing toxicity. It is widely recognized that the principles of pharmacokinetics and pharmacodynamics are critical to determining an adequate dose-response relationship. There has been an increased involvement of the CNS to infection from opportunistic and endemic fungi over the last several decades due to establishment of solid-organ and bone marrow transplantation as well as immunosuppression from HIV. In this regard it has become critical to define optimal dosing regimens by an understanding of the processes which govern delivery of an antifungal agent to the targeted CNS site of involvement. The objective of this review is to: i) summarize published experimental and clinical antifungal pharmacokinetics; and ii) examine the relationship between CNS antifungal pharmacokinetics and efficacy. Examination of these studies reveal marked variability among antifungal drugs with regard to cerebrospinal fluid and brain parenchymal penetration. Formal examination of the relationship between CNS antifungal pharmacokinetics and efficacy are limited. The few experimental studies available suggest that brain parenchymal kinetics is a superior predictor of antifungal efficacy than cerebrospinal fluid concentrations. PMID:17696807

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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-...

  6. 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...

  7. 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 ...

  8. 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...

  9. 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...

  10. Antifungal therapy with an emphasis on biofilms

    PubMed Central

    Pierce, Christopher G.; Srinivasan, Anand; Uppuluri, Priya; Ramasubramanian, Anand K.; López-Ribot, José Luis

    2013-01-01

    Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins, constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, microbial communities displaying resistance to most antifungal agents. A better understanding of fungal biofilms provides for new opportunities for the development of urgently needed novel antifungal agents and strategies. PMID:24011516

  11. Antifungal therapy with an emphasis on biofilms.

    PubMed

    Pierce, Christopher G; Srinivasan, Anand; Uppuluri, Priya; Ramasubramanian, Anand K; López-Ribot, José L

    2013-10-01

    Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, microbial communities displaying resistance to most antifungal agents. A better understanding of fungal biofilms provides for new opportunities for the development of urgently needed novel antifungal agents and strategies. PMID:24011516

  12. The synergistic potential of the azole fungicides prochloraz and propiconazole toward a short α-cypermethrin pulse increases over time in Daphnia magna.

    PubMed

    Kretschmann, Andreas; Gottardi, Michele; Dalhoff, Kristoffer; Cedergreen, Nina

    2015-05-01

    Pyrethroid insecticides are highly toxic to non-target aquatic invertebrates. Their high toxicity is synergized when co-occurring with azole fungicides in the aquatic environment. Little is known about the importance of synergy, when pyrethroids only occur during a short pulse of a few hours, as it is likely to happen in the environment, nor about the persistence of synergy over time. This study analyzed the synergistic potential of the fungicides propiconazole and prochloraz toward Daphnia magna, when exposed to a pulse (7.2 h) of α-cypermethrin at different concentrations (average pulse concentrations 0.07-11 nM). Immobilization was monitored during exposure and a subsequent recovery period (87.5h) with and without continuous co-exposure to the azoles (1.4 and 1.7 μM, respectively). EC50 values for immobilization decreased exponentially over time with a higher rate in the presence of the azoles. EC50 values for α-cypermethrin determined at the end of the experiment were 3.3±0.5 nM in the absence of azoles and 0.26±0.04, and 0.08±0.01 nM in the presence of propiconazole and prochloraz, respectively. The synergistic potential of the azoles was strongly dependent on time: no synergism could be detected during the pulse, but with azole co-exposure EC50 values decreased during the recovery period by a factor of up to 13 (propiconazole) and 61 (prochloraz) compared to values without azole exposure. Such high synergistic ratios have not been reported for pesticide mixtures in literature before. Our findings highlight that a pulse of the pyrethroid α-cypermethrin is synergized far beyond the actual pulse and beyond standardized test durations. Long post-exposure times are therefore mandatory in order to capture full synergism. PMID:25797530

  13. 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...

  14. Genomic pathways to antifungal discovery.

    PubMed

    Monk, Brian C; Cannon, Richard D

    2002-12-01

    The limitations of the therapeutic antifungals are becoming increasingly apparent in the clinic due to their modest efficacy against life-threatening systemic fungal infections. These antifungals belong to only a few structural classes that affect a small range of targets, some are quite toxic in humans while the use of others, particularly the azole drugs, has encouraged the emergence of resistant clinical isolates and the selection of innately resistant fungal pathogens. Only a few new drugs based on novel targets are in clinical development, and these may be insufficient to overcome the changing tide of fungal disease. In parallel with the successful completion of the Saccharomyces cerevisiae and human genome sequencing projects, an increasing number of genome sequencing projects are being initiated and completed for significant fungal pathogens. The growing repository of genomic information, which is complemented by decades of genetic and biochemical study, is now available for genome-wide analysis of gene function and for incisive inter-genomic comparison, with the S. cerevisiae and human genomes providing key points of reference. Functional genomic and comparative genomic techniques, many of which were developed with S. cerevisiae, are being applied to fungal pathogens with the aim of obtaining an integrated view of fungal biology and to extract targets suitable for drug discovery. This review describes some of these techniques, their limitations and their increasing contribution to the antifungal discovery process through effective gene annotation, target identification and prioritization, and in the optimization of antifungal leads. PMID:12570738

  15. 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

  16. Antifungal Application of Nonantifungal Drugs

    PubMed Central

    Stylianou, Marios; Kulesskiy, Evgeny; Lopes, José Pedro; Granlund, Margareta; Wennerberg, Krister

    2014-01-01

    Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candida activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against Candida spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candida activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candida agents, which allows for the design of novel therapies against invasive candidiasis. PMID:24277040

  17. A Prototype Antifungal Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hudson, Sarah P.; Mobbs, Ashley N.; Hoare, Todd R.; Iwata, Naomi G.; Fink, Gerald R.

    2011-01-01

    Purpose. To design a contact lens to treat and prevent fungal ocular infections. Methods. Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. Results. Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. Conclusions. An econazole-eluting contact lens could be used as a treatment for fungal ocular infections. PMID:21527380

  18. Advancements in Topical Antifungal Vehicles.

    PubMed

    Kircik, Leon H

    2016-02-01

    The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles.

    J Drugs Dermatol. 2016;15(Suppl 2):s44-48. PMID:26885798

  19. 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

  20. 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

  1. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

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

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. Ketoconazole Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%. Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence). Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. Ciclopirox Ciclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungals Clotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies. Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms. Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar. Authors' conclusions Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis. Plain Language Summary Antifungal treatments applied to the skin to treat seborrhoeic dermatitis Background Seborrhoeic dermatitis is a chronic inflammatory skin condition found throughout the world, with rashes with varying degrees of redness, scaling and itching. It affects people of both sexes but is more common among men. The disease usually starts after puberty and can lead to personal discomfort and cosmetic concerns when rashes occur at prominent skin sites. Drugs that act against moulds, also called antifungal agents, have been commonly used on their own or in combination. Review question Do antifungal treatments applied to the skin clear up the rashes and itching of seborrhoeic dermatitis? Study characteristics We included 51 studies with 9052 participants. Trials typically were four weeks long, and very few trials were longer. In all, 24 studies had some involvement of pharmaceutical companies such as funding or employment of the researchers. Key results Particpants taking ketoconazole were 31% less likely than those given placebo to have symptoms that persisted at four weeks of follow-up. This was seen in eight studies with 2520 participants, but wide variation was noted between studies. Ketoconazole was as effective as steroids but had 44% fewer side effects. Without causing more side effects, ciclopirox was 21% more effective than placebo in achieving clinical clearance of rashes. Treatment effect on redness, itching or scaling symptoms of the skin was less clear. Evidence was insufficient to conclude that that one antifungal was superior to other antifungals, but this observation was based on few studies. Ketoconazole and ciclopirox are the most heavily investigated antifungals and are more effective than placebo. Other antifungals might have similar effects, but data are insufficient to underpin this. Common side effects were increased skin redness or itching, burning sensation and hair loss. No studies measured quality of life. Only one study reported on percentage of compliance in different treatment groups. Other studies used surrogates such as acceptability to represent compliance. We therefore could not assess the effect of compliance on treatment outcomes. One study on patients with HIV reported no clear effects of treatments. Quality of the evidence Evidence for the effects of ketoconazole compared with placebo or a steroid was assessed to be of low quality. Evidence derived from comparison of ciclopirox versus placebo was assessed to be of moderate quality. Better quality studies with longer follow-up and better reporting are needed to enlarge the evidence base for antifungals.

  2. 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

  3. Antifungals: Mechanism of Action and Drug Resistance.

    PubMed

    Prasad, Rajendra; Shah, Abdul Haseeb; Rawal, Manpreet Kaur

    2016-01-01

    There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise. PMID:26721281

  4. 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

  5. Antifungal Activity of Citrus Essential Oils.

    PubMed

    Jing, Li; Lei, Zhentian; Li, Ligai; Xie, Rangjin; Xi, Wanpeng; Guan, Yu; Sumner, Lloyd W; Zhou, Zhiqin

    2014-03-27

    Citrus essential oils (CEOs) are a mixture of volatile compounds consisting mainly of monoterpene hydrocarbons and are widely used in the food and pharmaceutical industries because of their antifungal activities. To face the challenge of growing public awareness and concern about food and health safety, studies concerning natural biopreservatives have become the focus of multidisciplinary research efforts. In the past decades, a large amount of literature has been published on the antifungal activity of CEOs. This paper reviews the advances of research on CEOs and focuses on their in vitro and food antifungal activities, chemical compositions of CEOs, and the methods used in antifungal assessment. Furthermore, the antifungal bioactive components in CEOs and their potential mechanism of action are summarized. Finally, the applications of CEOs in the food industry are discussed in an attempt to provide new information for future utilization of CEOs in modern industries. PMID:24628448

  6. Antifungal susceptibilities of Paecilomyces species.

    PubMed

    Aguilar, C; Pujol, I; Sala, J; Guarro, J

    1998-07-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  7. Antifungal Susceptibilities of Paecilomyces Species

    PubMed Central

    Aguilar, C.; Pujol, I.; Sala, J.; Guarro, J.

    1998-01-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  8. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  9. 21 CFR 333.250 - Labeling of antifungal drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antifungal drug products. 333.250... Antifungal Drug Products § 333.250 Labeling of antifungal drug products. (a) Statement of identity. The... “antifungal.” (b) Indications. The labeling of the product states, under the heading “Indications,” the...

  10. 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... Antifungal Drug Products § 333.250 Labeling of antifungal drug products. (a) Statement of identity. The... “antifungal.” (b) Indications. The labeling of the product states, under the heading “Indications,” the...

  11. Antifungal Activity of Isothiocyanates and Related Compounds

    PubMed Central

    Drobnica, Ľ.; Zemanová, M.; Nemec, P.; Antoš, K.; Kristián, P.; Štullerová, A.; Knoppová, V.; Nemec, P.

    1967-01-01

    Data are presented concerning the antifungal activity of 11 natural isothiocyanates and 27 synthetized analogues in Aspergillus niger, Penicillium cyclopium, and Rhizopus oryzae, as well as in 13 additional saprophytic and parasitic fungi. A remarkable antifungal activity was observed in some analogues of benzylisothiocyanate and β-phenylethylisothiocyanate. The latter-mentioned compounds have not been described previously. In the group of benzylisothiocyanates, a correlation, which was inversely proportional, was detected between ed100 values for A. niger and R. oryzae and the corresponding molar solubilities of compounds in water. In contradistinction, no relationship was observed between antifungal activity and chemical reactivity of investigated derivatives. PMID:6049294

  12. 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

  13. Dosing of antifungal agents in obese people.

    PubMed

    Payne, Kenna D; Hall, Ronald G

    2016-02-01

    Obesity is a worldwide epidemic associated with multiple comorbidities that increase the risk of hospitalization. Very little pharmacokinetic data are available for antifungal agents in obesity, as this population is often excluded from drug development studies and these agents are less commonly used than other antimicrobials. Systemic antifungal therapy for invasive candidiasis continues to have a high failure rate, and dose optimization in obesity provides an opportunity for improvement. Based on currently available data, some antifungals should be dosed based on total body weight (i.e. fluconazole), while others should not be adjusted for increased body weight (i.e. posaconazole). More studies are needed to determine if and when dosing changes are needed for many of the antifungal agents. Therefore, drug therapy regimens should be individually evaluated for dose optimization due to body weight. PMID:26641135

  14. Antifungal activities of some indole derivatives.

    PubMed

    Xu, Hui; Wang, Qin; Yang, Wen-Bin

    2010-01-01

    Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide. PMID:20737910

  15. 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...

  16. Antifungal activity of octyl gallate.

    PubMed

    Fujita, Ken-ichi; Kubo, Isao

    2002-12-15

    Antifungal activities of propyl (C3), octyl (C8) and dodecyl (C12) gallates (3,4,5-trihydroxybenzoate) were tested against Saccharomyces cerevisiae ATCC7754 and Zygosaccharomyces bailii ATCC 60483. Octyl gallate was found to be the only active compound with the minimum fungicidal concentration of 25 microg/ml (89 microM) against S. cerevisiae and of 50 microg/ml (177 microM) against Z. bailii, respectively. The inactivation study showed that octyl gallate was fungicidal against both S. cerevisiae and Z. bailii at any stage of growth. These fungicidal activities were not influenced by pH values. Octyl gallate at 100 microg /ml reduced plasma membrane fluidity to 48% of control. On the other hand, dodecyl gallate at the same concentration reduced it to 76% of control. Only octyl gallate inhibited glucose-induced medium acidification, indicating direct or indirect inhibition of plasma membrane H +-ATPase. The primary fungicidal activity of octyl gallate comes from its ability to act as a nonionic surface-active agent (surfactant), though it can not be inferred that membrane damage, such as a decrease in the membrane fluidity, is the only cause of the lethal effect. PMID:12371654

  17. 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... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  18. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  19. Antifungal drug discovery: the process and outcomes

    PubMed Central

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  20. Synthesis, antifungal activities and qualitative structure activity relationship of carabrone hydrazone derivatives as potential antifungal agents.

    PubMed

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-01-01

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents. PMID:24619221

  1. Antifungal activity of five species of Polygala

    PubMed Central

    Johann, Susana; Mendes, Beatriz G.; Missau, Fabiana C.; de Resende, Maria A.; Pizzolatti, Moacir G.

    2011-01-01

    Crude extracts and fractions of five species of Polygala – P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa – were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC) assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 μg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 μg/mL and 250 μg/mL, respectively) and C. gattii (both with MICs of 250 μg/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 μg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain. PMID:24031724

  2. Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

    PubMed

    Hahn-Ast, C; Felder, L; Mayer, K; Mückter, S; Ruhnke, M; Hein, R; Hellmich, M; Schwab, K; Rachow, T; Brossart, P; von Lilienfeld-Toal, M

    2016-05-01

    Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis. PMID:27021301

  3. 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

  4. 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

  5. Antifungal activity of ajoene derived from garlic.

    PubMed

    Yoshida, S; Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H; Nakagawa, S

    1987-03-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml. PMID:3555334

  6. Antifungal activity of ajoene derived from garlic.

    PubMed Central

    Yoshida, S; Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H; Nakagawa, S

    1987-01-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml. Images PMID:3555334

  7. 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

  8. Antifungal activity of 10 Guadeloupean plants.

    PubMed

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. PMID:23280633

  9. Efflux pump proteins in antifungal resistance

    PubMed Central

    Prasad, Rajendra; Rawal, Manpreet K.

    2014-01-01

    It is now well-known that the enhanced expression of ATP binding cassette (ABC) and major facilitator superfamily (MFS) proteins contribute to the development of tolerance to antifungals in yeasts. For example, the azole resistant clinical isolates of the opportunistic human fungal pathogen Candida albicans show an overexpression of Cdr1p and/or CaMdr1p belonging to ABC and MFS superfamilies, respectively. Hence, azole resistant isolates display reduced accumulation of therapeutic drug due to its rapid extrusion and that facilitates its survival. Considering the importance of major antifungal transporters, the focus of recent research has been to understand the structure and function of these proteins to design inhibitors/modulators to block the pump protein activity so that the drug already in use could again sensitize resistant yeast cells. The review focuses on the structure and function of ABC and MFS transporters of Candida to highlight the recent advancement in the field. PMID:25221515

  10. Antifungal Effect of Brachyglottis repanda Ethanol Extract

    PubMed Central

    Yook, Chan Nam; Na, Young Soon; Choi, Hwa Jung; You, Il Soo; Baek, Jong Min

    2010-01-01

    The crude ethanol extract of B. repanda showed the cytotoxic activity against Polio virus (25% activity at 150 μg/disk) and the minor cytotoxic activity against BSC cells (African green monkey kidney) . However, the crude ethanol extract of B. repanda was non-toxic to murine leukaemia cells CCL 46 P388D1 (IC50, > 62,500 ng/ml) . Cytotoxic and antifungal activities were strongly shown by Fr. 64-3 which was eluted with 90% CH3CN/H2O, 100% CH3CN, and 50% CH3CN/H2O (SM 2 at 150 μg/disk) . The fraction 64-3 also showed the most cytotoxic activity against murine leukaemia cells (128 mg, IC50 10,051 ng/ml at 75 μg/disk) . These results suggest that this fraction has a potent antifungal activity against the dermatophytic fungus Trichophyton mentagrophytes ATCC 28185. PMID:24278514

  11. Antibacterial and antifungal activities of Angiopteris evecta.

    PubMed

    Khan, M R; Omoloso, A D

    2008-07-01

    The leaves, stem bark, stem heart wood, root and tubers of Angiopteris evecta were successively extracted with petrol, dichloromethane, ethyl acetate, butanol and methanol. All the fractions exhibited a wider spectrum of antibacterial activity. The dichloromethane and ethyl acetate fractions of the leaves and stem bark were particularly good and were the only fractions exhibiting antifungal activity. All fractions of the tuber with the exception of petrol, exhibited very good antibacterial activity. PMID:18505704

  12. Antifungal potential of Spilanthes calva after inoculation of Piriformospora indica.

    PubMed

    Rai, M K; Varma, A; Pandey, A K

    2004-12-01

    We investigated the influence of Piriformospora indica on the antifungal principle of Spilanthes calva, a plant of high commercial value. An antifungal efficacy was shown by aqueous and petroleum ether extracts of S. calva against Fusarium oxysporum and Trichophyton mentagrophytes. The petroleum ether extract of S. calva was more effective than the aqueous extract in inoculated as well as uninoculated plants. The antifungal activity of the plant was enhanced due to the increase in spilanthol content after inoculation of P. indica. PMID:15601453

  13. Antifungal activity of some coleus species growing in nilgiris.

    PubMed

    Nilani, P; Duraisamy, B; Dhanabal, P S; Khan, Saleemullah; Suresh, B; Shankar, V; Kavitha, K Y; Syamala, G

    2006-07-01

    The in vitro antifungal activity of solvent extracts of Coleus forskohlii, Coleus blumei and Coleus barbatus were compared by testing against some pathogenic fungi like Aspergillus niger, Aspergillusfumigatus, Aspergillus ruantii, Proteus vulgaris and Candida albicans. The petroleum ether extract of Coleus forskohlii and Coleus barbatus exhibited significant antifungal activity against all the selected organisms. The extracts of Coleus blumei did not show any significant antifungal activity against the selected organisms. PMID:22557230

  14. Antifungal Activity of Maytenin and Pristimerin

    PubMed Central

    Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

    2012-01-01

    Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

  15. Hydroxytyrosol expresses antifungal activity in vitro.

    PubMed

    Zoric, Natasa; Horvat, Igor; Kopjar, Nevenka; Vucemilovic, Ante; Kremer, Dario; Tomic, Sinisa; Kosalec, Ivan

    2013-08-01

    Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml⁻¹ and 6.25 mgml⁻¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts. PMID:23721186

  16. 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

  17. Econazole imprinted textiles with antifungal activity.

    PubMed

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3μg/cm(2)) was reproducible and stable up to 4months storage at 25°C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8°C, which enabled a larger drug release at 32°C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. PMID:26883854

  18. 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

  19. New antifungal agents for the systemic mycoses.

    PubMed

    Ringel, S M

    1990-02-01

    The azoles are the prominent broad spectrum oral antifungal agents in use or under clinical investigation for the systemic mycoses. This class of antifungal agents is represented by the marketed drug ketoconazole (Nizoral) and the experimental triazoles furthest along in clinical trials in the United States, itraconazole and fluconazole. Ketoconazole use is limited by its side effect profile and activity spectrum. Itraconazole appears to be better tolerated and less toxic to liver function, does not cause adrenal suppression and is more active against Aspergillus and Sporothrix schenckii. Fluconazole appears to be a highly promising agent due its highly favorable pharmacokinetic profile; it is water soluble, is well tolerated, is not metabolized to inactive constituents, it has a long half-life and, unlike the other azoles, high cerebrospinal fluid levels are readily attained for consideration in meningeal mycoses. It remains to be determined what place these new triazoles have in managing immunosuppressed patients including those with acquired immune deficiency syndrome known as AIDS. Other experimental antifungal agents, including ambruticin, amphotericin B methyl ester and saramycetin are also described. Sales figures are presented of drugs marketed in the United States for the systemic mycoses and reflect the growing problem of fungal diseases in the population. PMID:2157984

  20. 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

  1. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02

    PubMed Central

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  2. Caspofungin as secondary antifungal prophylaxis and subsequent maintenance antifungal prophylaxis therapy in hematological malignancy patients

    PubMed Central

    Liu, Mingjuan; Li, Yan; Zhao, Xiaoli; Zhang, Yongqing; Zhai, Bing; Zhang, Qingyi; Wang, Lijun; Zhao, Yu; Li, Honghua; Wang, Quanshun; Gao, Chunji; Huang, Wenrong; Yu, Li

    2015-01-01

    Aim: This study aimed to investigate the efficacy and safety of caspofungin as secondary antifungal prophylaxis (SAP) and subsequent maintenance therapy for SAP in hematological malignancy patients. Methods: Forty four patients receiving caspofungin for SAP and 43 patients not receiving any SAP agents during their subsequent chemotherapy or HSCT were reviewed retrospectively. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. Results: The recurrence rate of IFD in 44 patients with caspofungin for SAP was 9.1% (4/44), which was much lower than that in 43 patients without SAP (9.1% vs 46.5%, P = 0.000). Patients with SAP had lower recurrent IFD-related mortality than that without SAP (12.5% vs 55.6%, P = 0.131). Among the 44 patients with SAP, caspofungin continued as maintenance antifungal prophylaxis therapy in 18 patients after neutropenia and oral medication became possible, while voriconazole in 14 patients and itraconazole in 12 patients. The recurrent IFD occurred in 2, 1, 1 patient respectively. There was no statistical difference in recurrence rates among different maintenance antifungal prophylaxis therapies (P = 0.922). No severe adverse events were observed during SAP treatment. Conclusions: Caspofungin is effective and safe to prevent IFD recurrence in hematological malignancy patients undergoing chemotherapy or HSCT. A subsequent maintenance antifungal prophylaxis therapy of oral voriconazole or itraconazole instead of caspofungin after caspofungin as SAP during neutropenia is as effective as caspofungin given constantly. PMID:26380020

  3. Cuticular antifungals in spiders: density- and condition dependence.

    PubMed

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

    2014-01-01

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

  4. 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

  5. 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...

  6. Cuticular Antifungals in Spiders: Density- and Condition Dependence

    PubMed Central

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

    2014-01-01

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

  7. Antifungal activity of Rubia tinctorum, Rhamnus frangula and Caloplaca cerina.

    PubMed

    Manojlovic, N T; Solujic, S; Sukdolak, S; Milosev, M

    2005-03-01

    The results of a preliminary antifungal screening of the methanol extracts and the major anthraquinone aglycones, alizarin and emodin, of Rubia tinctorum and Rhamnus frangula in comparison with the antifungal activity of the anthraquinone-containing lichen Caloplaca cerina and its main secondary metabolite parietin are reported. PMID:15752641

  8. Antifungal ether diglycosides from Matayba guianensis Aublet.

    PubMed

    de Assis, Polyana A; Theodoro, Phellipe N E T; de Paula, José E; Araújo, Ana J; Costa-Lotufo, Letícia V; Michel, Sylvie; Grougnet, Raphaël; Kritsanida, Marina; Espindola, Laila S

    2014-03-01

    Since the 1960s, fungal infections have become a major worldwide public health problem. Antifungal treatments have many limitations, such as toxicity and resistance. Matayba guianensis Aublet (Sapindaceae) was chemically investigated as part of our ongoing search for lead molecules against fungi in the Brazilian Cerrado biome. The ethanolic extract of M. guianensis root bark revealed the presence of two previously unreported ether diglycosides: matayoside E (1) and F (2) with anti Candida activity, along with two known compounds: cupanioside (3) and stigmasterol (4). PMID:24485783

  9. Chemical modification of antifungal polyene macrolide antibiotics

    NASA Astrophysics Data System (ADS)

    Solovieva, S. E.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2011-02-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  10. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  11. Emerging Threats in Antifungal-Resistant Fungal Pathogens

    PubMed Central

    Sanglard, Dominique

    2016-01-01

    The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is tempting to combine several drugs to achieve better therapeutic efficacy. In the recent years, several novel resistance patterns have been observed, including antifungal resistance originating from environmental sources in Aspergillus fumigatus and the emergence of simultaneous resistance to different antifungal classes (multidrug resistance) in different Candida species. This review will summarize these current trends. PMID:27014694

  12. EFFECT OF CONAZOLE FUNGICIDES ON REPRODUCTIVE DEVELOPMENT IN THE FEMALE RAT

    EPA Science Inventory

    Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500 ppm), myclobutanil (M) (100, 500, or 2000 ppm), or triadimefon (T) (100, 500, or 1800 ppm) from gestation day 6 to postn...

  13. 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...

  14. Antifungal drug resistance of oral fungi.

    PubMed

    Niimi, Masakazu; Firth, Norman A; Cannon, Richard D

    2010-02-01

    Fungi comprise a minor component of the oral microbiota but give rise to oral disease in a significant proportion of the population. The most common form of oral fungal disease is oral candidiasis, which has a number of presentations. The mainstay for the treatment of oral candidiasis is the use of polyenes, such as nystatin and amphotericin B, and azoles including miconazole, fluconazole, and itraconazole. Resistance of fungi to polyenes is rare, but some Candida species, such as Candida glabrata and C. krusei, are innately less susceptible to azoles, and C. albicans can acquire azole resistance. The main mechanism of high-level fungal azole resistance, measured in vitro, is energy-dependent drug efflux. Most fungi in the oral cavity, however, are present in multispecies biofilms that typically demonstrate an antifungal resistance phenotype. This resistance is the result of multiple factors including the expression of efflux pumps in the fungal cell membrane, biofilm matrix permeability, and a stress response in the fungal cell. Removal of dental biofilms, or treatments to prevent biofilm development in combination with antifungal drugs, may enable better treatment and prevention of oral fungal disease. PMID:20155503

  15. Novel antifungal peptides from Ceylon spinach seeds.

    PubMed

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  16. Microbial Biotransformation to Obtain New Antifungals.

    PubMed

    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. PMID:26733974

  17. Dysregulation of Ion Homeostasis by Antifungal Agents

    PubMed Central

    Zhang, Yongqiang; Muend, Sabina; Rao, Rajini

    2012-01-01

    Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides. PMID:22493595

  18. 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. PMID:26733974

  19. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID:26848627

  20. Mechanisms of echinocandin antifungal drug resistance.

    PubMed

    Perlin, David S

    2015-09-01

    Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall-active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which is frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promotes the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin-resistance mechanism, along with cellular and clinical factors promoting resistance, will facilitate more effective strategies to overcome and prevent echinocandin resistance. PMID:26190298

  1. Antifungal Th Immunity: Growing up in Family

    PubMed Central

    Borghi, Monica; Renga, Giorgia; Puccetti, Matteo; Oikonomou, Vasileios; Palmieri, Melissa; Galosi, Claudia; Bartoli, Andrea; Romani, Luigina

    2014-01-01

    Fungal diseases represent an important paradigm in immunology since they can result from either the lack of recognition or over-activation of the inflammatory response. Current understanding of the pathophysiology underlying fungal infections and diseases highlights the multiple cell populations and cell-signaling pathways involved in these conditions. A systems biology approach that integrates investigations of immunity at the systems-level is required to generate novel insights into this complexity and to decipher the dynamics of the host–fungus interaction. It is becoming clear that a three-way interaction between the host, microbiota, and fungi dictates the types of host–fungus relationship. Tryptophan metabolism helps support this interaction, being exploited by the mammalian host and commensals to increase fitness in response to fungi via resistance and tolerance mechanisms of antifungal immunity. The cellular and molecular mechanisms that provide immune homeostasis with the fungal biota and its possible rupture in fungal infections and diseases will be discussed within the expanding role of antifungal Th cell responses. PMID:25360137

  2. Pharmacokinetics and Pharmacodynamics of Antifungals in Children: Clinical Implications

    PubMed Central

    Autmizguine, Julie; Guptill, Jeffrey T.; Cohen-Wolkowiez, Michael; Benjamin, Daniel K.; Capparelli, Edmund V.

    2014-01-01

    Invasive fungal disease (IFD) remains life-threatening in premature infants and immunocompromised children despite the recent development of new antifungal agents. Optimal dosing of antifungals is one of the few factors clinicians can control to improve outcomes of IFD. However, dosing in children cannot be extrapolated from adult data because IFD pathophysiology, immune response, and drug disposition differ from adults. We critically examined the literature on pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and highlight recent developments in treating pediatric IFD. To match adult exposure in pediatric patients, dosing adjustment is necessary for almost all antifungals. In young infants, the maturation of renal and metabolic functions occurs rapidly and can significantly influence drug exposure. Fluconazole clearance doubles from birth to 28 days of life and, beyond the neonatal period, agents like fluconazole, voriconazole, and micafungin require higher dosing than in adults due to faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. Pharmacodynamics principles of antifungals mostly rely on in vitro and in vivo models but very few pharmacodynamics studies specifically address IFD in children. Exposure-response relationship may differ in younger children compared with adults, especially in infants with invasive candidiasis who are at higher risk of disseminated disease and meningoencephalitis, and by extension severe neurodevelopmental impairment. Micafungin is the only antifungal agent for which a specific target of exposure was proposed based on a neonatal hematogenous Candida meningoencephalitis animal model. In this review, we found that pediatric data on drug disposition of newer triazoles and echinocandins are lacking, dosing of older antifungals such as fluconazole and amphotericin B products still need optimization in young infants, and that target PK/PD indices need to be clinically validated for almost all antifungals in children. A better understanding of age-specific PK and PD of new antifungals in infants and children will help improve clinical outcomes of IFD by informing dosing and identifying future research areas. PMID:24872147

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

    PubMed

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

    2009-10-14

    A novel antifungal protein (Pr-2) was identified from pumpkin rinds using water-soluble extraction, ultrafiltration, cation exchange chromatography, and reverse-phase high-performance liquid chromatography. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry indicated that the protein had a molecular mass of 14865.57 Da. Automated Edman degradation showed that the N-terminal sequence of Pr-2 was QGIGVGDNDGKRGKR-. The Pr-2 protein strongly inhibited in vitro growth of Botrytis cinerea, Colletotrichum coccodes, Fusarium solani, Fusarium oxysporum, and Trichoderma harzianum at 10-20 microM. The results of confocal laser scanning microscopy and SYTOX Green uptake demonstrated that its effective region was the membrane of the fungal cell surface. In addition, this protein was found to be noncytotoxic and heat-stable. Taken together, the results of this study indicate that Pr-2 is a good candidate for use as a natural antifungal agent. PMID:19807165

  4. Synthesis, antifungal activity and QSAR study of 2-arylhydroxynitroindoles.

    PubMed

    Kokurkina, Galina V; Dutov, Mikhail D; Shevelev, Svyatoslav A; Popkov, Sergey V; Zakharov, Alexey V; Poroikov, Vladimir V

    2011-09-01

    A series of 2-arylhydroxynitroindoles were prepared and tested for antifungal activity in vitro. The preliminary bioassays indicated that some compounds are comparable to the commercial fungicide (triadimefon). To further explore the structure-activity relationships, the data set of the seventeen structures and their quantitative values of antifungal activities were used for QSAR modeling. Based on the obtained QSAR models four new chemical compounds were designed, synthesized and tested in fungicidal assays. Reasonable correspondence between the experimental and predicted values of antifungal activity was observed. PMID:21802177

  5. Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches

    PubMed Central

    Roemer, Terry; Krysan, Damian J.

    2014-01-01

    Invasive, life-threatening fungal infections are an important cause of morbidity and mortality, particularly for patients with compromised immune function. The number of therapeutic options for the treatment of invasive fungal infections is quite limited when compared with those available to treat bacterial infections. Indeed, only three classes of molecules are currently used in clinical practice and only one new class of antifungal drugs has been developed in the last 30 years. Here we summarize the unmet clinical needs of current antifungal therapy, discuss challenges inherent to antifungal drug discovery and development, and review recent developments aimed at addressing some of these challenges. PMID:24789878

  6. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey

    PubMed Central

    Akan, Hamdi; Atilla, Erden

    2016-01-01

    Despite the development of various guidelines, the approach to antifungal treatment in stem cell transplantation centers differs according to country or even between centers. This led to the development of another survey that aims to understand the antifungal treatment policies of Turkish stem cell transplantation centers. Although there has been an increasing trend towards the use of diagnostic-based treatments in Turkey in the last few years, empirical treatment is still the main approach. The practices of the stem cell transplantation centers reflect the general trends and controversies in this area, while there is a considerable use of antifungal combination therapy. PMID:25913124

  7. Antifungal susceptibility testing of Candida spp. by relative growth measurement at single concentrations of antifungal agents.

    PubMed Central

    Odds, F C

    1992-01-01

    The relative growth (percentage of growth relative to control growth) of 496 isolates representing six Candida species was assessed as a means of determining in vitro susceptibilities of the isolates in microdilution plate wells containing single concentrations of each of seven antifungal agents. The relative growth data were highly reproducible. With flucytosine and amorolfine they correlated well with MICs, but for an azole antifungal agent, terconazole, they did not correlate with MICs. Distributions of relative growth percentages for different Candida spp. showed significant differences in species susceptibility to individual agents. For example, C. albicans was less susceptible than the other species to amorolfine; C. parapsilosis isolates were particularly susceptible to terbinafine; and C. glabrata, C. guilliermondii, and C. krusei isolates were less susceptible than C. albicans to fluconazole and ketoconazole but equally susceptible as or more susceptible than C. albicans to itraconazole. Differential patterns of susceptibility to individual azole antifungal agents were noted for some individual strains as well as for Candida spp. PMID:1416856

  8. Antifungal 3-butylisocoumarins from Asteraceae-Anthemideae.

    PubMed

    Engelmeier, D; Hadacek, F; Hofer, O; Lutz-Kutschera, G; Nagl, M; Wurz, G; Greger, H

    2004-01-01

    Seven new naturally occurring 3-butylisocoumarins were isolated and identified from lipophilic extracts of aerial as well as underground organs: corfin (17) and 3'-hydroxycorfin (18) from the roots of Chamaemelum mixtum and (-)-(R)-2'-methoxydihydroartemidin (5), (+)-(S,R)-epoxyartemidin (6a), dracumerin (12), (+)-(R)-(E)-3'-hydroxyartemidin (13), and capillarin isovalerate (20) from various organs of Artemisia dracunculus (tarragon). Furthermore, six known derivatives, artemidiol (7), (E/Z)-artemidin (11), capillarin (19), artemidinol (21), 8-hydroxyartemidin (22), and 8-hydroxycapillarin (23), were obtained. The antifungal activities of all naturally occurring derivatives were determined in a germ-tube inhibition test against a susceptible strain of rice blast fungus Pyricularia grisea. The 3-butyl side-chain is a prerequisite for high activity. Eleven structurally related synthetic derivatives were additionally tested to explore the influence of structural characteristics on activity. Benlate, blasticidin S, kresoxim-methyl, griseofulvin, and the carrot phytoalexin 6-methoxymellein all served as positive controls. PMID:14738379

  9. 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

  10. Action of antifungal imidazoles on Staphylococcus aureus.

    PubMed Central

    Sud, I J; Feingold, D S

    1982-01-01

    In Staphylococcus aureus, using the imidazoles miconazole and ketoconazole, detailed studies of minimal inhibitory concentrations, kinetics of growth, viability, and release of intracellular K+ confirm that the two imidazoles work differently in this bacterium. Miconazole is bactericidal at low concentrations and causes release of cellular K+. Ketoconazole has no bactericidal effect at any tested concentration and has little effect on K+ permeability of S. aureus; it slows growth at high concentration. This is reflected in a low minimal inhibitory concentration for miconazole and a high one for ketoconazole. The probable mechanisms of the bacteriostatic and bactericidal effects of the imidazoles are discussed in light of these results and the previously described antifungal mechanisms of the drugs. alpha-Tocopherol blocks the action of both imidazoles. PMID:6291453

  11. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID:26826375

  12. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    PubMed

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

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. PMID:26323525

  13. Research to Identify Effective Antifungal Agents, 1991 Annual Report.

    SciTech Connect

    Schreck, Carl

    1991-09-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990). The objectives of the present study was to evaluate up to 10 candidate fungicides.

  14. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

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

    PubMed

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; 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

  16. Antioxidant and antifungal activity of Verbena officinalis L. leaves.

    PubMed

    Casanova, E; García-Mina, J M; Calvo, M I

    2008-09-01

    The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform, ethyl acetate and 50% methanolic extracts of Verbena officinalis leaves were investigated. The activity of different fractions of 50% methanolic extract and some isolated compounds were also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered as excellent and readily available sources of natural antifungal and antioxidant compounds. PMID:18498054

  17. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  18. Chemosensitization as a Means to Augment Commercial Antifungal Agents

    PubMed Central

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

    2012-01-01

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

  19. Antifungal activity of polymer-based copper nanocomposite coatings

    NASA Astrophysics Data System (ADS)

    Cioffi, Nicola; Torsi, Luisa; Ditaranto, Nicoletta; Sabbatini, Luigia; Zambonin, Pier Giorgio; Tantillo, Giuseppina; Ghibelli, Lina; D'Alessio, Maria; Bleve-Zacheo, Teresa; Traversa, Enrico

    2004-09-01

    Eukaryotes, such as fungi, can be harmful pathogen agents, and the control of their bioactivity is critical as humans are eukaryote organisms, too. Here, copper/polymer nanocomposites are proposed as antifungal spinnable coatings with controlled copper-releasing properties. The tests of the bioactivity show that fungal growth is inhibited on the nanocomposite-coated plates, and the antifungal activity can be modulated by controlling the Cu nanoparticle loading.

  20. Design, Synthesis, DFT Study and Antifungal Activity of Pyrazolecarboxamide Derivatives.

    PubMed

    Mu, Jin-Xia; Shi, Yan-Xia; Yang, Ming-Yan; Sun, Zhao-Hui; Liu, Xing-Hai; Li, Bao-Ju; Sun, Na-Bo

    2016-01-01

    A series of novel pyrazole amide derivatives were designed and synthesized by multi-step reactions from phenylhydrazine and ethyl 3-oxobutanoate as starting materials, and their structures were characterized by NMR, MS and elemental analysis. The antifungal activity of the title compounds was determined. The results indicated that some of title compounds exhibited moderate antifungal activity. Furthermore, DFT calculations were used to study the structure-activity relationships (SAR). PMID:26760990

  1. Isolation of Bacillus amyloliquefaciens Strains with Antifungal Activities from Meju

    PubMed Central

    Lee, Hwang A; Kim, Jeong Hwan

    2012-01-01

    Bacilli with fibrinolytic activities were isolated from traditionally-prepared Meju and some of these strains showed strong antifungal activities. One isolate, MJ1-4, showed the strongest antifungal activity. MJ1-4 and other isolates were identified as B. amyloliquefaciens strains by recA gene sequencing and RAPD-PCR results. B. amyloliqufaciens MJ1-4 efficiently inhibited an Aspergillus spp.-producing aflatoxin B1 (AFB1) and a Penicillium spp.-producing ochratoxin (OTA) in addition to other fungi. Antifungal activity of B. amyloliquefaciens MJ1-4 culture reached its maximum (40 AU/mg protein) in LB or TSB medium around 48 hr at 37°C. Antifungal activity of the concentrated culture supernatant was not decreased significantly by protease treatments, implying that the antifungal substance might not be a simple peptide or protein. Considering its antifungal and fibrinolytic activities together, B. amyloliquefaciens MJ1-4 can serve as a starter for fermented soyfoods such as Cheonggukjang and Doenjang. PMID:24471064

  2. Oral fungi in HIV: challenges in antifungal therapies.

    PubMed

    Nittayananta, W

    2016-04-01

    Oral candidiasis (OC) caused by Candida species is a common fungal infection among HIV-infected individuals. Despite the wide use of antiretroviral therapy (ART) resulting in a declined prevalence, OC remains the most common oral lesions seen in those living with HIV/AIDS. Various topical and systemic antifungal drugs are available to treat OC. However, due to the patients' immunodeficiency and the nature of OC as biofilm-associated infection, relapse is frequently observed after cessation of antifungal therapy. In addition, long-term antifungal therapy may lead to drug resistance. This review article addressed three major challenges in the treatment of OC in HIV infection including antifungal drug resistance, biofilm-associated infection of OC, and the host underlying immunodeficiency. To reduce the risks of antifungal drug resistance, the author recommends that future studies should focus on herbal plant-derived compounds with antifungal activity that may be used in combination with the drugs. Also, it is recommended that more research should be carried out to explore how to enhance the host innate immunity against oral Candida. PMID:27109279

  3. Antifungal Hydrolases in Pea Tissue 1

    PubMed Central

    Mauch, Felix; Mauch-Mani, Brigitte; Boller, Thomas

    1988-01-01

    Chitinase and β-1,3-glucanase purified from pea pods acted synergistically in the degradation of fungal cell walls. The antifungal potential of the two enzymes was studied directly by adding protein preparations to paper discs placed on agar plates containing germinated fungal spores. Protein extracts from pea pods infected with Fusarium solani f.sp. phaseoli, which contained high activities of chitinase and β-1,3-glucanase, inhibited growth of 15 out of 18 fungi tested. Protein extracts from uninfected pea pods, which contained low activities of chitinase and β-1,3-glucanase, did not inhibit fungal growth. Purified chitinase and β-1,3-glucanase, tested individually, did not inhibit growth of most of the test fungi. Only Trichoderma viride was inhibited by chitinase alone, and only Fusarium solani f.sp. pisi was inhibited by β-1,3-glucanase alone. However, combinations of purified chitinase and β-1,3-glucanase inhibited all fungi tested as effectively as crude protein extracts containing the same enzyme activities. The pea pathogen, Fusarium solani f.sp. pisi, and the nonpathogen of peas, Fusarium solani f.sp. phaseoli, were similarly strongly inhibited by chitinase and β-1,3-glucanase, indicating that the differential pathogenicity of the two fungi is not due to differential sensitivity to the pea enzymes. Inhibition of fungal growth was caused by the lysis of the hyphal tips. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:16666407

  4. 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

  5. Antifungal activity of plant and bacterial ureases.

    PubMed

    Becker-Ritt, A B; Martinelli, A H S; Mitidieri, S; Feder, V; Wassermann, G E; Santi, L; Vainstein, M H; Oliveira, J T A; Fiuza, L M; Pasquali, G; Carlini, C R

    2007-12-01

    Ureases (EC 3.5.1.5) are nickel-dependent metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Produced by plants, fungi and bacteria, but not by animals, ureases share significant homology and similar mechanisms of catalysis, although differing in quaternary structures. While fungal and plant ureases are homo-oligomeric proteins of 90 kDa subunits, bacterial ureases are multimers of two (e.g. Helicobacter pylori) or three subunit complexes. It has been proposed that in plants these enzymes are involved in nitrogen bioavailability and in protection against pathogens. Previous studies by our group have shown that plant ureases, but not a bacterial (Bacillus pasteurii) urease, display insecticidal activity. Herein we demonstrate that (Glycine max) embryo-specific soybean urease, jackbean (Canavalia ensiformis) major urease and a recombinant H. pylori urease impair growth of selected phytopathogenic fungi at sub-micromolar concentrations. This antifungal property of ureases is not affected by treatment of the proteins with an irreversible inhibitor of the ureolytic activity. Scanning electron microscopy of urease-treated fungi suggests plasmolysis and cell wall injuries. Altogether, our data indicate that ureases probably contribute to the plant arsenal of defense compounds against predators and phytopathogens and that the urease defense mechanism is independent of ammonia release from urea. PMID:17825863

  6. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    PubMed

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2015-01-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  7. 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

  8. 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...

  9. Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids

    NASA Astrophysics Data System (ADS)

    Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.

    2011-05-01

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.

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

    PubMed

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, 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

  11. In Search of the Holy Grail of Antifungal Therapy

    PubMed Central

    Chapman, Stanley W.; Sullivan, Donna C.; Cleary, John D.

    2008-01-01

    The ideal antifungal agent remains an elusive goal for treatment of life-threatening systemic fungal infections. Such an agent would have broad antifungal activity, low rates of resistance, flexible routes of administration, few associated adverse events, and limited drug-drug interactions. Only three of the seven classes of antifungal agents currently available are suitable for treatment of systemic infection: the polyenes, the azoles, and the echinocandins. None match all the characteristics of an ideal agent, the Holy Grail of antifungal therapy. Academia and industry need to collaborate in the search for new lead antifungal compounds using traditional screening methods as well as the new pharmacogenomics methods. Enhancing efficacy and reducing toxicity of the currently available therapeutic agents is also another important avenue of study. As an example, the Mycosis Research Center at the University of Mississippi Medical Center has identified pyogenic polyenes in commercial preparations of amphotericin B deoxycholate which correlate with infusion related toxicities. A highly purified formulation of amphotericin B appears promising, with a better therapeutic index compared to its parent compound as evidenced by results of in vitro and in vivo studies reviewed in this presentation. PMID:18596853

  12. Antifungal activity of sakurasosaponin from the root extract of Jacquinia flammea.

    PubMed

    García-Sosa, K; Sánchez-Medina, A; Álvarez, Sandra L; Zacchino, S; Veitch, N C; Simá-Polanco, P; Peña-Rodriguez, L M

    2011-07-01

    The methanolic crude extract from the roots of Jacquinia flammea showed moderate antifungal activity against dermatophytes and very strong antifungal activity against Colletotrichum gloeosporioides. The bioassay-guided purification of the extract, using a combination of vacuum-liquid chromatography and high performance liquid chromatography, allowed the identification of sakurasosaponin as the main metabolite responsible for the antifungal activity. PMID:21740284

  13. Antifungal plant defensins: mechanisms of action and production.

    PubMed

    Vriens, Kim; Cammue, Bruno P A; Thevissen, Karin

    2014-01-01

    Plant defensins are small, cysteine-rich peptides that possess biological activity towards a broad range of organisms. Their activity is primarily directed against fungi, but bactericidal and insecticidal actions have also been reported. The mode of action of various antifungal plant defensins has been studied extensively during the last decades and several of their fungal targets have been identified to date. This review summarizes the mechanism of action of well-characterized antifungal plant defensins, including RsAFP2, MsDef1, MtDef4, NaD1 and Psd1, and points out the variety by which antifungal plant defensins affect microbial cell viability. Furthermore, this review summarizes production routes for plant defensins, either via heterologous expression or chemical synthesis. As plant defensins are generally considered non-toxic for plant and mammalian cells, they are regarded as attractive candidates for further development into novel antimicrobial agents. PMID:25153857

  14. Peptide-based Antifungal Therapies against Emerging Infections

    PubMed Central

    Matejuk, A.; Leng, Q.; Begum, M.D.; Woodle, M.C.; Scaria, P.; Chou, S-T; Mixson, A.J.

    2010-01-01

    Acquired drug resistance to mycotic infections is rapidly emerging as a major medical problem. Opportunistic fungal infections create therapeutic challenges, particularly in high risk immunocompromised patients with AIDS, cancer, and those undergoing transplantation. Higher mortality and/or morbidity rates due to invasive mycosis have been increasing over the last 20 years, and in light of growing resistance to commonly used antibiotics, novel antifungal drugs and approaches are required. Currently there is considerable interest in antifungal peptides that are ubiquitous in plant and animal kingdoms. These small cationic peptides may have specific targets or may be multifunctional in their mechanism of action. On the basis of recent advances in protein engineering and solid phase syntheses, the utility and potential of selected peptides as efficient antifungal drugs with acceptable toxicity profiles are being realized. This review will discuss recent advances in peptide therapy for opportunistic fungal infections. PMID:20495663

  15. 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

  16. Steroid Interference with Antifungal Activity of Polyene Antibiotics

    PubMed Central

    Zygmunt, Walter A.; Tavormina, Peter A.

    1966-01-01

    Wide differences exist among the polyene antibiotics, nystatin, rimocidin, filipin, pimaricin, and amphotericin B, with reference to steroid interference with their antifungal activities against Candida albicans. Of the numerous steroids tested, ergosterol was the only one which effectively antagonized the antifungal activity of all five polyene antibiotics. The antifungal activities of nystatin and amphotericin B were the least subject to vitiation by the addition of steroids other than ergosterol, and those of filipin, rimocidin, and pimaricin were the most sensitive to interference. Attempts to delineate the structural requirements of steroids possessing polyene-neutralizing activity in growing cultures of C. albicans are discussed. The ultraviolet absorbance of certain antibiotic steroid combinations was also studied. PMID:16349686

  17. 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

  18. Fungal virulence genes as targets for antifungal chemotherapy.

    PubMed Central

    Perfect, J R

    1996-01-01

    Fungal virulence genes have now met the age of molecular pathogenesis. The definition of virulence genes needs to be broad so that it encompasses the focus on molecular antifungal targets and vaccine epitopes. However, in the broad but simple definition of a virulence gene, there will be many complex genetic and host interactions which investigators will need to carefully define. Nevertheless, with the increasing numbers of serious fungal infections produced by old and newly reported organisms, the paucity of present antifungal drugs, and the likelihood of increasing drug resistance, the need for investigations into understanding fungal virulence at the molecular level has never been more important. PMID:8807043

  19. Silicon Incorporated Morpholine Antifungals: Design, Synthesis, and Biological Evaluation.

    PubMed

    Jachak, Gorakhnath R; Ramesh, Remya; Sant, Duhita G; Jorwekar, Shweta U; Jadhav, Manjusha R; Tupe, Santosh G; Deshpande, Mukund V; Reddy, D Srinivasa

    2015-11-12

    Known morpholine class antifungals (fenpropimorph, fenpropidin, and amorolfine) were synthetically modified through silicon incorporation to have 15 sila-analogues. Twelve sila-analogues exhibited potent antifungal activity against different human fungal pathogens such as Candida albicans, Candida glabrata, Candida tropicalis, Cryptococcus neoformans, and Aspergillus niger. Sila-analogue 24 (fenpropimorph analogue) was the best in our hands, which showed superior fungicidal potential than fenpropidin, fenpropimorph, and amorolfine. The mode of action of sila-analogues was similar to morpholines, i.e., inhibition of sterol reductase and sterol isomerase enzymes of ergosterol synthesis pathway. PMID:26617963

  20. Atmospheric pressure cold plasma as an antifungal therapy

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

    A microhollow cathode based, direct-current, atmospheric pressure, He/O2 (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.

  1. 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.

  2. Antifungal activity of three mouth rinses--in vitro study.

    PubMed

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans. PMID:16758789

  3. Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action.

    PubMed

    Rosen, Theodore; Stein Gold, Linda F

    2016-03-01

    In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals. PMID:27074700

  4. Antibacterial and antifungal metal based triazole Schiff bases.

    PubMed

    Chohan, Zahid H; Hanif, Muhammad

    2013-10-01

    A new series of four biologically active triazole derived Schiff base ligands (L(1)-L(4)) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1-16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species. PMID:22803673

  5. [Derivatives of 2-thiocyanobenzoic acid with antifungal activity].

    PubMed

    Montanari, L; Pavanetto, F; Modena, T; Mazza, M

    1984-11-01

    A series of amides, esters and thioesters of 2-thiocyanobenzoic acid were synthesised and tested for antifungal activity in vitro and in vivo against various strains of fungus pathological to plants. The phytotoxicity against representative plants was studied in parallel. The substances were prepared by condensation of suitable mercaptobenzamides with cyanogen bromide or of 2-thiocyanobenzoyl chloride with amines, alcohols or mercaptans. This research showed in vitro antifungal activity of some N-monosubstituted amides and in vivo activity of some N-monosubstituted and N,N-disubstituted amides of 2-thiocyanobenzoic acid which have the same protective activity towards P. viticola as Zineb. PMID:6519264

  6. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology

    PubMed Central

    Ashbee, H. Ruth; Barnes, Rosemary A.; Johnson, Elizabeth M.; Richardson, Malcolm D.; Gorton, Rebecca; Hope, William W.

    2014-01-01

    The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics–pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents. PMID:24379304

  7. Antifungal Activities of SCY-078 (MK-3118) and Standard Antifungal Agents against Clinical Non-Aspergillus Mold Isolates

    PubMed Central

    Lamoth, Frédéric

    2015-01-01

    The limited armamentarium of active and oral antifungal drugs against emerging non-Aspergillus molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-d-glucan synthase inhibitor SCY-078 were tested in vitro against 135 clinical non-Aspergillus mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against Mucoromycotina and Fusarium spp. However, SCY-078 was highly active against Paecilomyces variotii and was the only compound displaying some activity against notoriously panresistant Scedosporium prolificans. PMID:25896696

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

    PubMed

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

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. PMID:26680221

  9. 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

  10. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

    Pałkowski, Łukasz; Błaszczyński, Jerzy; Skrzypczak, Andrzej; Błaszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Kożuszko, Sylwia; Gospodarek, Eugenia; Słowiński, Roman; Krysiński, 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

  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. [In vitro antifungal activity of nitroxoline. Preliminary clinical results].

    PubMed

    Cancet, B; Amgar, A

    1987-06-01

    Nitroxoline is an oxyquinoline derivative with a large antifungical activity. The fungistatic activity of nitroxoline is greater against Candida albicans than against Torulopsis glabrata, Candida tropicalis and Candida krusei. The MIC are compatible with urinary concentrations of nitroxoline. These preliminary clinical results favor the use of nitroxoline in the management of fungal urinary tract infections. PMID:3309833

  13. Properties and mechanisms of action of naturally occurring antifungal peptides.

    PubMed

    van der Weerden, Nicole L; Bleackley, Mark R; Anderson, Marilyn A

    2013-10-01

    Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity. They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security. Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells. To date, most research on antimicrobial peptides has focused on their activity against bacteria. Several antimicrobial peptides specifically target fungal cells and are not active against bacteria. Others with broader specificity often have different mechanisms of action against bacteria and fungi. This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants, mammals, amphibians, insects, crabs, spiders, and fungi. While antimicrobial peptides were originally proposed to act via membrane permeabilization, the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell. PMID:23381653

  14. Prediction of antifungal activity of gemini imidazolium compounds.

    PubMed

    Pałkowski, Łukasz; Błaszczyński, Jerzy; Skrzypczak, Andrzej; Błaszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Kożuszko, Sylwia; Gospodarek, Eugenia; Słowiński, Roman; Krysiński, 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

  15. Successful management of renal mucormycosis with antifungal therapy and drainage

    PubMed Central

    Devana, Sudheer K.; Bora, Girdhar S.; Mavuduru, Ravimohan S.; Panwar, Pankaj; Kakkar, Nandita; Mandal, Arup K.

    2016-01-01

    We report a case of isolated extensive renal mucormycosis in an immunocompetent adult, who was successfully managed conservatively without surgical debridement. To the best of our knowledge, this is the first case where antifungal therapy alone was sufficient even with such an extensive involvement. PMID:27127360

  16. Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs.

    PubMed

    Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M A; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E; Casadevall, Arturo; Gonçalves, Teresa

    2015-01-01

    The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. PMID:26711773

  17. [Yeasts in domestic animals: species identification and susceptibility to antifungals].

    PubMed

    Hamal, Petr; Koukalová, Dagmar

    2010-02-01

    Yeasts frequently colonize various kinds of domestic animals, but may also cause serious diseases. The aim of this study was to identify yeast isolates collected from dogs, cows and pigs, and to determine their in vitro antifungal susceptibility. Fifty-six yeast isolates from dogs (n = 24), cows (n = 20), and pigs (n = 12) were investigated. Appearance of colonies grown on Sabouraud agar, micromorphology on rice agar, as well as assimilation and fermentation of various carbon and nitrogen sources were evaluated. Susceptibility to six antifungals (flucytosine, amphotericin B, miconazole, ketoconazole, itraconazole and fluconazole) was determined semiquantitatively using the commercially available Fungitest kit (Bio-Rad Laboratories). Ten yeast species were identified in dogs with relatively even distribution. On the other hand, cow and pig were clearly dominated by Candida krusei (from 7 species) and Candida rugosa (from 5 species), respectively. Further, most of yeast isolates exhibited good susceptibility to the antifungals tested particularly to amphotericin B, ketoconazole and itraconazole. Based on results, it can be concluded that significant differences in the species spectrum and distribution were documented between groups of yeasts from dogs, cows and pigs. This is probably due to different environmental conditions and the endogenous origin of the yeast isolates. Mostly good susceptibility to systemic antifungals should positively influence the therapy of diseases caused by yeasts in veterinary medicine. PMID:20401831

  18. The Antifungal Polyketide Ambruticin Targets the HOG Pathway▿

    PubMed Central

    Vetcher, Leandro; Menzella, Hugo G.; Kudo, Toshiaki; Motoyama, Takayuki; Katz, Leonard

    2007-01-01

    The polyketide ambruticin is an attractive candidate for drug development as an antifungal agent, but its mechanism of action has not yet been elucidated. Here we present evidence that ambruticin exerts its effect by targeting HOG, the osmotic stress control pathway, through Hik1, a group III histidine kinase. PMID:17698623

  19. Research to Identify Effective Antifungal Agents, 1992 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-03-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990 and Schreck et al. 1991). The objectives of the present study were to select and evaluate up to 10 candidate fungicides.

  20. 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 ...

  1. Using Aspergillus nidulans to identify antifungal drug resistance mutations.

    PubMed

    He, Xiaoxiao; Li, Shengnan; Kaminskyj, Susan G W

    2014-02-01

    Systemic fungal infections contribute to at least 10% of deaths in hospital settings. Most antifungal drugs target ergosterol (polyenes) or its biosynthetic pathway (azoles and allylamines), or beta-glucan synthesis (echinocandins). Antifungal drugs that target proteins are prone to the emergence of resistant strains. Identification of genes whose mutations lead to targeted resistance can provide new information on those pathways. We used Aspergillus nidulans as a model system to exploit its tractable sexual cycle and calcofluor white as a model antifungal agent to cross-reference our results with other studies. Within 2 weeks from inoculation on sublethal doses of calcofluor white, we isolated 24 A. nidulans adaptive strains from sectoring colonies. Meiotic analysis showed that these strains had single-gene mutations. In each case, the resistance was specific to calcofluor white, since there was no cross-resistance to caspofungin (echinocandin). Mutation sites were identified in two mutants by next-generation sequencing. These were confirmed by reengineering the mutation in a wild-type strain using a gene replacement strategy. One of these mutated genes was related to cell wall synthesis, and the other one was related to drug metabolism. Our strategy has wide application for many fungal species, for antifungal compounds used in agriculture as well as health care, and potentially during protracted drug therapy once drug resistance arises. We suggest that our strategy will be useful for keeping ahead in the drug resistance arms race. PMID:24363365

  2. 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...

  3. Determination of antifungal, biochemical and physiological features of Trichoderma koningiopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trichoderma koningiopsis is a species that has been recently identified and has not yet been published, but is in press. Due to the absence of reported data on this species, antifungal, biochemical and physiological features were analyzed for the Trichoderma koningiopsis strain isolated from root se...

  4. Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus neoformans isolates.

    PubMed

    Arsic Arsenijevic, Valentina; Pekmezovic, Marina G; Meis, Jacques F; Hagen, Ferry

    2014-06-01

    Molecular typing and antifungal susceptibility testing of 34 clinical Serbian Cryptococcus neoformans isolates from 25 patients was retrospectively performed. Amplified fragment length polymorphism (AFLP) fingerprinting was used for genotyping, whereas a novel real-time PCR was used to determine the mating- and serotype. The antifungals amphotericin B, 5-fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the antifungal susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3; 8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating-serotype αA, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV harboured serotype D isolates with either the a (n = 2; 5.9%) or α (n = 8; 23.5%) mating-type allele. The isolates (n = 3; 8.8%) that were found to be genotype AFLP3/VNIII had the hybrid mating- and serotype combination aA-αD. In vitro antifungal susceptibility testing showed that all isolates were susceptible to amphotericin B, voriconazole and posaconazole. Low resistance level was observed for fluconazole (n = 1; 2.9%) and 5-fluorocytosine. (n = 2; 5.8%). A large percentage of isolates was found to be susceptible dose dependent to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among clinical C. neoformans isolates from immunocompromised patients in Serbia. C. neoformans from HIV-negative patients were significantly less susceptible to 5-fluorocytosine (P < 0.01). Correlation between genotypes and antifungal susceptibility was not observed. PMID:24438323

  5. Evaluation of the antifungal activity and modulation between Cajanus cajan (L.) Millsp. leaves and roots ethanolic extracts and conventional antifungals

    PubMed Central

    Brito, Samara A.; Rodrigues, Fabíola F. G.; Campos, Adriana R.; da Costa, José G. M.

    2012-01-01

    Background: The use and investigation of natural products with antimicrobial activity from vegeral source have been reported by several researchers. Cajanus cajan (Fabaceae) is a multiple use specie mainly as human food. In popular medicine, diverse parts of the plant are used as sedative and to treat cough, hepatitis, and diabetes. Materials and Methods: This study shows the characterization of secondary metabolites present in ehtanolic extracts from leaves and roots of Cajanus cajan by phytochemical prospection. The evaluation of the antifungal activity was performed by the microdilution method, and from the subinhibitory concentrations (MIC 1/8) the modulatory activity of antifungical (fluconazole and ketoconazole) was analyzed by the direct contact assay against C. albicans ATCC40006, Candida krusei ATCC 6538 and Candida tropicalis ATCC 40042. Results: The results showed the presence of tannins, flavonoids, and alkaloids in both extracts as the clinically relevant antifungal activity. The modulatory potential is presented by the antifungal tested against yeasts. Conclusion: The extracts studied here have demonstrated to be a new therapeutic source to treat these microorganism-associated diseases. PMID:22701281

  6. Study of the antifungal activity of Bacillus vallismortis ZZ185 in vitro and identification of its antifungal components.

    PubMed

    Zhao, Zhenzhen; Wang, Qiushuo; Wang, Kaimei; Brian, Kemp; Liu, Changhong; Gu, Yucheng

    2010-01-01

    An endophytic Bacillus vallismortis ZZ185 was isolated from healthy stems of the plant Broadleaf Holly (Ilex latifolia Thunb) collected in Nanjing, China. Both the culture filtrate and the n-butanol extract of strain ZZ185 showed strong growth inhibition activity in vitro against the phytopathogens Fusarium graminearum, Alternaria alternata, Rhizoctonia solani, Cryphonectria parasitica and Phytophthora capsici. The results showed that the filtrate and extract reduced the symptoms of wheat seedlings infected with A. alternata and F. graminearum by about 90% and 50%, respectively, based on the comparison of the lengths of zones on the seminal roots showing cortical browning with those of the roots of uninfected controls. The antifungal activity of the culture filtrate was significantly correlated with cell growth of strain ZZ185. The active metabolite in the filtrate was relatively thermally stable with more than 50% of the antifungal activity of the culture filtrate being retained even after being held at 121 degrees C for 30 min. Meanwhile, the antifungal activity of the filtrate against the growth of A. alternata and F. graminearum remained almost unchanged (>75%) when the culture was exposed to a pH ranging from 1 to 8, but significantly reduced after the filtrate had been exposed to basic conditions. From the n-butanol extract of the filtrate, the antifungal compounds were isolated as a mixture of Bacillomycin D (n-C14) and Bacillomycin D (iso-C15). The strong antifungal activity implied that the endophytic B. vallismortis ZZ185 and its bioactive components might provide an alternative resource for the biocontrol of plant diseases. PMID:19717300

  7. Synthesis and antifungal activity of derivatives of 2- and 3-benzofurancarboxylic acids.

    PubMed

    Hejchman, Elzbieta; Ostrowska, Kinga; Maciejewska, Dorota; Kossakowski, Jerzy; Courchesne, William E

    2012-11-01

    We found that amiodarone has potent antifungal activity against a broad range of fungi, potentially defining a new class of antimycotics. Investigations into its molecular mechanisms showed amiodarone mobilized intracellular Ca2+, which is thought to be an important antifungal characteristic of its fungicidal activity. Amiodarone is a synthetic drug based on the benzofuran ring system, which is contained in numerous compounds that are both synthetic and isolated from natural sources with antifungal activity. To define the structural components responsible for antifungal activity, we synthesized a series of benzofuran derivatives and tested them for the inhibition of growth of two pathogenic fungi, Cryptococcus neoformans and Aspergillus fumigatus, to find new compounds with antifungal activity. We found several derivatives that inhibited fungal growth, two of which had significant antifungal activity. We were surprised to find that calcium fluxes in cells treated with these derivatives did not correlate directly with their antifungal effects; however, the derivatives did augment the amiodarone-elicited calcium flux into the cytoplasm. We conclude that antifungal activity of these new compounds includes changes in cytoplasmic calcium concentration. Analyses of these benzofuran derivatives suggest that certain structural features are important for antifungal activity. Antifungal activity drastically increased on converting methyl 7-acetyl-6-hydroxy-3-methyl-2-benzofurancarboxylate (2b) into its dibromo derivative, methyl 7-acetyl-5-bromo-6-hydroxy-3-bromomethyl-2-benzofurancarboxylate (4). PMID:22892340

  8. Conventional and alternative antifungal therapies to oral candidiasis.

    PubMed

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-10-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis. PMID:24031562

  9. Synthesis, characterization, and antifungal activity of novel quaternary chitosan derivatives.

    PubMed

    Li, Rongchun; Guo, Zhanyong; Jiang, Pingan

    2010-09-01

    Three novel quaternary chitosan derivatives were successfully synthesized by reaction of chloracetyl chitosan (CACS) with pyridine (PACS), 4-(5-chloro-2-hydroxybenzylideneamino)-pyridine (CHPACS), and 4-(5-bromo-2-hydroxybenzylideneamino)-pyridine (BHPACS). The chemical structure of the prepared chitosan derivatives was confirmed by Fourier transform infrared (FT-IR) and (13)C nuclear magnetic resonance ((13)C NMR) and their antifungal activity against Cladosporium cucumerinum, Monilinia fructicola, Colletotrichum lagenarium, and Fusarium oxysporum was assessed. Comparing with the antifungal activity of chitosan, CACS, and PACS, CHPACS and BHPACS exhibited obviously better inhibitory effects, which should be related to the synergistic reaction of chitosan itself with the grafted 2-[4-(5-chloro-2-hydroxybenzylideneamino)-pyridyl]acetyl and 2-[4-(5-bromo-2-hydroxybenzylideneamino)-pyridyl]acetyl. PMID:20615498

  10. Antifungal activity of biflavones from Taxus baccata and Ginkgo biloba.

    PubMed

    Krauze-Baranowska, Mirosława; Wiwart, Marian

    2003-01-01

    Bilobetin and 4'''-O-methylamentoflavone were isolated and identified in the needles of Taxus baccata, for the first time in this species. The antifungal activity of biflavones from T. baccata and Ginkgo biloba, namely amentoflavone, 7-O-methylamentoflavone, bilobetin, ginkgetin, sciadopitysin and 2,3-dihydrosciadopitysin towards the fungi Alternaria alternata, Fusarium culmorum, Cladosporium oxysporum was determined employing computer-aided image analysis couplet to a microscope. Bilobetin exhibited a significant antifungal activity with values of ED50 14, 11 and 17 microM respectively. This compound completely inhibited the growth of germinating tubes of Cladosporium oxysporum and Fusarium culmorum at a concentration 100 microM. Activity of ginkgetin and 7-O-methylamentoflavone towards Alternaria alternata was stronger than that of bilobetin. Moreover, slight structural changes in the cell wall of Alternaria alternata exposed to ginkgetin at concentration of 200 microM were observed. PMID:12622229

  11. Purification of angularin, a novel antifungal peptide from adzuki beans.

    PubMed

    Ye, X Y; Ng, T B

    2002-03-01

    An antifungal peptide was isolated from the adzuki bean with a procedure involving affinity chromatography on Affi-gel blue gel and ion exchange chromatography on CM-Sepharose. The protein designated angularin was adsorbed on both types of chromatographic media and possessed a molecular weight of 8 kDa. Angularin exhibited antifungal activity against a variety of fungal species including Mycospharella arachidiocola and Botrytis cinerea. It inhibited mycelial growth in B. cinerea with an IC50 of 14.3 microM. Fusarium oxysporum and Rhizoctonia solani were not inhibited. Angularin demonstrated inhibitory activity on translation in the rabbit reticulocyte lysate system (IC50 = 8.0 microM) but did not affect proliferation of splenocytes. The activity of HIV-1 reverse transcriptase was inhibited in the presence of angularin. Its N-terminal sequence was GEPGQKE. PMID:11931582

  12. Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives.

    PubMed

    Cheng, Jing-Li; Zheng, Min; Yao, Ting-Ting; Li, Xiao-Liang; Zhao, Jin-Hao; Xia, Min; Zhu, Guo-Nian

    2015-01-01

    In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification. PMID:25290081

  13. INNATE ANTIFUNGAL IMMUNITY: THE KEY ROLE OF PHAGOCYTES

    PubMed Central

    Brown, Gordon D.

    2012-01-01

    Fungal diseases have emerged as significant causes of morbidity and mortality, particularly in immune compromised individuals, prompting greater interest in understanding the mechanisms of host resistance to these pathogens. Consequently, the last few decades have seen a tremendous increase in our knowledge of the innate and adaptive components underlying the protective (and non-protective) mechanisms of anti-fungal immunity. What has emerged from these studies is that phagocytic cells are essential for protection, and that defects in these cells compromises the hosts ability to resist fungal infection. This review covers the functions of phagocytes in innate anti-fungal immunity, along with selected examples of the strategies that are used by fungal pathogens to subvert these defences. PMID:20936972

  14. Conventional and alternative antifungal therapies to oral candidiasis

    PubMed Central

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-01-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis. PMID:24031562

  15. Antifungal metabolites from fungal endophytes of Pinus strobus.

    PubMed

    Sumarah, Mark W; Kesting, Julie R; Sørensen, Dan; Miller, J David

    2011-10-01

    The extracts of five foliar fungal endophytes isolated from Pinus strobus (eastern white pine) that showed antifungal activity in disc diffusion assays were selected for further study. From these strains, the aliphatic polyketide compound 1 and three related sesquiterpenes 2-4 were isolated and characterized. Compound 2 is reported for the first time as a natural product and the E/Z conformational isomers 3 and 4 were hitherto unknown. Additionally, the three known macrolides; pyrenophorol (5), dihydropyrenophorin (6), and pyrenophorin (7) were isolated and identified. Their structures were elucidated by spectroscopic analyses including 2D NMR, HRMS and by comparison to literature data where available. The isolated compounds 1, 2, and 5 were antifungal against both the rust Microbotryum violaceum and Saccharomyces cerevisae. PMID:21632082

  16. Rondonin an antifungal peptide from spider (Acanthoscurria rondoniae) haemolymph

    PubMed Central

    Riciluca, K.C.T.; Sayegh, R.S.R.; Melo, R.L.; Silva, P.I.

    2012-01-01

    Antimicrobial activities were detected in the haemolymph of the spider Acanthoscurrria rondoniae. A novel antifungal peptide, rondonin, was purified by reverse phase high performance liquid chromatography (RP-HPLC). Rondonin has an amino acid sequence of IIIQYEGHKH and a molecular mass of 1236.776 Da. This peptide has identity to a C-terminal fragment of the “d” subunit of haemocyanin from the spiders Eurypelma californicum and Acanthoscurria gomesiana. A synthetic peptide mimicking rondonin had identical characteristics to those of the isolated material, confirming its sequence. The synthetic peptide was active only against fungus. These data led us to conclude that the antifungal activity detected in the plasma of these spiders is the result of enzymatic processing of a protein that delivers oxygen in the haemolymph of many chelicerate. Several studies have suggested that haemocyanins are involved in the arthropod immune system, and the activity of this haemocyanin fragment reinforces this idea. PMID:24371568

  17. Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species.

    PubMed

    Paredes, Katihuska; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2016-04-01

    Scopulariopsisis an emerging opportunistic fungus characterized by its high resistance to antifungal therapies. We have developed a murine model of disseminated infection in immunosuppressed animals by intravenous inoculation ofScopulariopsis brevicaulisandScopulariopsis brumptii, the most clinically relevant species, in order to evaluate their virulence and their responses to conventional antifungal treatments. Survival and tissue burden studies showed thatS. brumptiiwas more virulent thanS. brevicaulis The three drugs tested, liposomal amphotericin B, posaconazole, and voriconazole, prolonged the survival of mice infected withS. brumptii, but none showed efficacy againstS. brevicaulis The different therapies were only able to modestly reduce the fungal burden of infected tissue; however, in general, despite the high serum levels reached, they showed poor efficacy in the treatment of the infection. Unfortunately, the most effective therapy forScopulariopsisinfections remains unresolved. PMID:26787688

  18. 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 μg/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

  19. Structural characteristics of tenecin 3, an insect antifungal protein.

    PubMed

    Lee, Y T; Kim, D H; Suh, J Y; Chung, J H; Lee, B L; Lee, Y; Choi, B S

    1999-03-01

    Tenecin 3, an antifungal protein, previously isolated from the insect Tenebrio molitor, inhibits growth of the fungus Candida albicans. However, the antifungal mechanism and functions of tenecin 3 remain unknown. As an initial step to study the mechanism and functions, physical and structural properties of tenecin 3 were examined by circular dichroism (CD) analysis and 2D nuclear overhauser effect spectroscopy. These analyses suggest that tenecin 3 has a propensity of random structure with very loose turn-like elements. The CD results also indicate that this random structural propensity is not significantly affected by temperature, pH, and by the presence of organic solvents or sodium dodecyl sulfate (SDS) micelles. However, the hydrodynamic studies suggest that tenecin 3 is not in extended form in spite of its random structural feature. PMID:10204073

  20. Lectins but not antifungal proteins exhibit anti-nematode activity.

    PubMed

    Zhao, S; Guo, Y X; Liu, Q H; Wang, H X; Ng, T B

    2009-09-01

    A variety of lectins and antifungal proteins were tested for toxicity against the plant parasitic nematodes Ditylenchus dipsaci and Heterodera glycines. It was found that lectins from the mushrooms Xylaria hypoxylon, Agrocybe cylindracea and Tricholoma mongolicum (TML-1) were the most potent against D. dipsaci, with EC(50) being 4.7, 9, and 20mg/ml, respectively. Lectins from Pseudostellaria heterophylla, samta tomato, and the mushrooms T. mongolicum (TML-2), Ganoderma lucidum, and Boletus edulis, and antifungal proteins from Ginkgo biloba toward D. dipsaci and pumpkin Cucurbita moschata had much lower anti-nematode potencies and could be considered as inactive for practical purposes. All lectins except that from P.heterophylle were potent against H.glycines. PMID:21784014

  1. Antifungal Textiles Formed Using Silver Deposition in Supercritical Carbon Dioxide

    NASA Astrophysics Data System (ADS)

    Gittard, Shaun D.; Hojo, Daisuke; Hyde, G. Kevin; Scarel, Giovanna; Narayan, Roger J.; Parsons, Gregory N.

    2010-04-01

    The antifungal properties of two silver-coated natural cotton fiber structures prepared using a supercritical carbon dioxide (scCO2) solvent were examined. Scanning electron microscopy confirmed that the scCO2 process may be used to produce cotton fiber textiles with uniform silver nanoparticle coatings. A version of the Kirby-Bauer disk diffusion test was used to assess the ability of these textiles to inhibit fungal growth. Cotton fabric samples modified with Ag(hepta) and Ag(cod)(hfac) exhibited measurable zones of inhibition. On the other hand, the uncoated fabric had no zone of inhibition. Possible applications of antifungal textiles prepared using scCO2 processing include use in hospital uniforms and wound dressings.

  2. Pharmacognostic and antifungal investigations of Elaeocarpus ganitrus (Rudrakasha).

    PubMed

    Singh, B; Chopra, A; Ishar, M P S; Sharma, A; Raj, T

    2010-03-01

    Rudrakasha is the dried bead obtained from the ripe fruit of Elaeocarpus ganitrus Roxb. (Family: Elaeocarpaceae). Microscopic studies revealed the presence of a hard endocarp with lignified isodiametric sclereids, seeds with membranous seed coat, which enclosed a dense cellular endosperm comprising of calcium oxalate druses. Physicochemical parameters showed that total ash was 1.36 times and 1.56 times more than the acid insoluble ash and water-soluble ash, respectively. Further, ethanol had a maximum extractable value of 2.4% and moisture content was found to be 9.7%. Different extracts, petroleum ether, chloroform, ethanol and water were prepared. Chemically the extracts showed the presence of phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins. The extracts were evaluated for antifungal activity on different fungal strains. Chlorofom and ethanol extracts have high antifungal activity against Candida albicans. Whereas, chloroform, ethanol and water extracts showed moderate inhibition against Aspergillus niger. PMID:20838538

  3. 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

  4. Antibacterial and antifungal activities of nitroxoline Mannich bases.

    PubMed

    Medić-Sarić, M; Maysinger, D; Movrin, M; Dvorzak, I

    1980-01-01

    The in vitro activity of nitroxoline and its Mannich bases against bacteria and fungi was investigated. Nitroxoline and its derivative with diisopropylamine as an amino component, exhibited the highest antimicrobial activity. The optimum hydro/lipophilic properties (log P), both for antibacterial and antifungal activity, are about log P values of 2. The least effective compound was this nitroxoline Mannich base which has diethanolamine as an amino component. PMID:6771105

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

    PubMed

    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

  6. Efficacy of some natural compounds as antifungal agents

    PubMed Central

    Vengurlekar, Sudha; Sharma, Rajesh; Trivedi, Piyush

    2012-01-01

    Natural sources have been important for the development of new active molecules for many years. Various small molecules with unique chemical skeleton and potent bioactivities were discovered through various sources like plants, marine products, and microorganisms, etc., which are considered as very important part of the nature. A number of potent antifungals have been originated from various natural sources. This account describes structure and activities of selected agents isolated from various natural sources. PMID:23055634

  7. 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 14α-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

  8. Voriconazole: review of a broad spectrum triazole antifungal agent.

    PubMed

    Kofla, Grzegorz; Ruhnke, Markus

    2005-06-01

    Voriconazole is a second-generation triazole antifungal agent, structurally derived from fluconazole with an extended spectrum of activity against a wide variety of yeasts and moulds. Developed for the treatment of life-threatening fungal infections, it appears to be an effective therapy option for invasive aspergillosis, fluconazole-resistant candidiasis and refractory or less-common invasive fungal infections. It is available for both oral and intravenous administration and is characterised by an acceptable safety and tolerability spectrum. PMID:15957974

  9. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

  10. The Mediterranean red alga Asparagopsis taxiformis has antifungal activity against Aspergillus species.

    PubMed

    Genovese, Giuseppa; Leitner, Sandra; Minicante, Simona A; Lass-Flörl, Cornelia

    2013-09-01

    The red algae Asparagopsis taxiformis collected from the Straits of Messina (Italy) were screened for antifungal activity against Aspergillus species. EUCAST methodology was applied and extracts showed antifungal activity against A. fumigatus, A. terreus and A. flavus. The lowest minimum inhibitory concentrations observed were <0.15 mg ml(-1) and the highest were >5 mg ml(-1) for Aspergillus spp. tested. Agar diffusion assays confirmed antifungal activity of A. taxiformis extracts in Aspergillus species. PMID:23437896

  11. 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

  12. Innovative phytosynthesized silver nanoarchitectures with enhanced antifungal and antioxidant properties

    NASA Astrophysics Data System (ADS)

    Ortan, Alina; Fierascu, Irina; Ungureanu, Camelia; Fierascu, Radu Claudiu; Avramescu, Sorin Marius; Dumitrescu, Ovidiu; Dinu-Pirvu, Cristina Elena

    2015-12-01

    While in the early era of nanotechnology, nanoparticles of noble metals were obtained through expensive methods, using toxic chemical reagents, in the last decade attempts are made to obtain the desired chemical composition, size, morphology, and other properties by eco and green synthesis, using plants. The aim of this paper is to compare two extraction methods (hydroalcoholic extraction and microwave extraction) used to phytosynthesize silver nanoparticles, in terms of nanoparticle (NP) morphology, antioxidant, and antifungal action, using an European native plant, Anthriscus cerefolium (L.) Hoffm. The extracts and the obtained NPs were characterized by modern analytical techniques (GC-MS, UV-Vis, SEM, TEM) and by phytochemical assays (total flavonoids, total terpenoids and total phenolic content). The antifungal activity (evaluated using the Kirby-Bauer method, against Aspergillus niger and Penicillium hirsutum) and the antioxidant activity (determined by the DPPH assay and a chemiluminescence assay) revealed notable differences between the samples, differences due to the extraction procedure followed. Also, preliminary studies regarding the stability and the toxicity of the nanoparticles are presented. By using the microwave-assisted extraction, not only smaller particles (less than 10 nm) were obtained, but also with better antifungal and antioxidant properties than the ones obtained by classical extraction.

  13. 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 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/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

  14. An overview of antifungal peptides derived from insect.

    PubMed

    Faruck, Mohammad Omer; Yusof, Faridah; Chowdhury, Silvia

    2016-06-01

    Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases. PMID:26093218

  15. Design, Synthesis, and Antifungal Activity of New α-Aminophosphonates

    PubMed Central

    Rezaei, Zahra; Khabnadideh, Soghra; Zomorodian, Kamiar; Pakshir, Keyvan; Nadali, Setareh; Mohtashami, Nadia; Faghih Mirzaei, Ehsan

    2011-01-01

    α-Aminophosphonates are bioisosteres of amino acids and have several pharmacological activities. These compounds have been synthesized by various routes from reaction between amine, aldehyde, and phosphite compounds. In order to synthesize α-aminophosphonates, catalytic effect of CuCl2 was compared with FeCl3. Also all designed structures as well as griseofulvin were docked into the active site of microtubule (1JFF), using Autodock program. The results showed that the reactions were carried out in the presence of CuCl2 in lower yields, and also the time of reaction was longer in comparison with FeCl3. The chemical structures of the new compounds were confirmed by spectral analyses. The compounds were investigated for antifungal activity against several fungi in comparison with griseofulvin. An indole-derived bis(α-aminophosphonates) with the best negative ΔG in docking study showed maximum antifungal activity against Microsporum canis, and other investigated compounds did not have a good antifungal activity. PMID:25954522

  16. 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 1α, 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

  17. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

    PubMed Central

    Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

    2012-01-01

    Background Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Methods Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. Results The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. Conclusion The present work has developed a new biocompatible antifungal PMMA denture base material. PMID:22969297

  18. 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

  19. 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

  20. In vitro Antifungal Activity of Luliconazole against Trichophyton spp.

    PubMed

    Maeda, Jun; Nanjoh, Yasuko; Koga, Hiroyasu; Toga, Tetsuo; Makimura, Koichi; Tsuboi, Ryoji

    2016-01-01

    The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of luliconazole against Trichophyton rubrum (14 strains) and Trichophyton mentagrophytes (14 strains), which are the most common cause of tinea, were compared with those of 6 topical antifungal drugs of lanoconazole, bifonazole, efinaconazole, liranaftate, naftifine and terbinafine. Luliconazole showed the most potent antifungal activity (MIC90 =0.00098 μg/ml and MFC90 =0.0078 μg/ml) among the compounds tested against the two species. Efinaconazole and bifonazole, the drug of azole-class, showed a large MFC/MIC ratio. On the other hand, these ratios of luliconazole and lanoconazole were as small as those of liranaftate, naftifine and terbinafine which are thought to possess fungicidal mechanism. These results suggest that luliconazole possesses fungicidal activity against both species of Trichophyton. In this study, we found that luliconazole had the most potent antifungal activity among the major topical antimycotics used in Japan and the US. Luliconazole would be the best-in-class drug for dermatophytosis in clinics. PMID:26936346

  1. 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 μg/mL at the concentration of obtained results warrant follow up through bioassay guided isolation of the active principles, future antiinfectious research. PMID:25362807

  2. Antifungal and antibacterial metabolites from a French poplar type propolis.

    PubMed

    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

  3. 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 μM 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

  4. 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 μM 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

  5. [Chemical constituents of Hyptis rhomboidea and their antifungal activity].

    PubMed

    Tang, Lu; Li, Xi-Feng; Yang, Sheng-Xiang; Qiu, Yan; Yuan, Ke

    2014-06-01

    The present work is to investigate the chemical constitutions of Hyptis rhomboidea and their antifungal activities. The compounds were isolated by Toyopearl HW-40, Sephadex LH-20, MCI-Gel CHP-20, RP-18, PTLC and silica column chromatographic methods and subjected to evaluate some monomers antifungal activity of eight kinds of plant pathogenic bacteria. Eleven compounds were isolated and identified as ethyl caffeate (1), ursolic acid (2), oleanolic acid (3), vanillactic acid (4), methyl rosmarinate (5), kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6) -beta-D-glucopyranoside (6), kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranoside (7), ilexgenin A (8), beta-amyrin (9), kaempferol 3-O-beta-D-glucopyranoside (astrgalin, 10) and cholest-5-ene-3beta, 4beta-diol (11). Compound 1 showed the strongest inhibitory effect on Sclerotinia sclerotiorum with the MIC 16.2 mg x L(-1), and compound 5 showed the strongest inhibitory effect on S. minor and Exserohilum turcicum with MIC 16.2, 8.1 mg x L(-1), respectively. All compounds were isolated from the H. rhomboidea for the first time, and compounds 1 and 5 showed antifungal activity. PMID:25244760

  6. Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

    PubMed

    Casanova, Bruna B; Muniz, Mauro N; de Oliveira, Thayse; de Oliveira, Luís Flavio; Machado, Michel M; Fuentefria, Alexandre M; Gosmann, Grace; Gnoatto, Simone C B

    2015-01-01

    Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents. PMID:26007181

  7. Antifungal Properties of Chenopodium ambrosioides Essential Oil Against Candida Species

    PubMed Central

    Chekem, Marie Stéphanie Goka; Lunga, Paul Keilah; Tamokou, Jean De Dieu; Kuiate, Jules Roger; Tane, Pierre; Vilarem, Gerard; Cerny, Muriel

    2010-01-01

    The essential oil of the aerial part (leaves, flowers and stem) of Chenopodium ambrosioides was obtained by hydrodistillation and its chemical composition analyzed by GC and GC/MS, which permitted the identification of 14 components, representing 98.8% of the total oil. Major components were α-terpinene (51.3%), p-cymene (23.4%) and p-mentha-1,8-diène (15.3%). The antifungal properties of this essential oil were investigated in vitro by the well diffusion and broth microdilution methods. The in vitro antifungal activity was concentration dependent and minimum inhibitory concentration values varied from 0.25 to 2 mg/mL. The in vivo antifungal activity was evaluated on an induced vaginal candidiasis rat model. The in vivo activity of the oil on mice vaginal candidiasis was not dose-dependent. Indeed, all the three tested doses; 0.1%, 1% and 10% led to the recovery of mice from the induced infection after 12 days of treatment. The effect of the essential oil on C. albicans ATCC 1663 fatty acid profile was studied. This oil has a relatively important dose-dependent effect on the fatty acids profile.

  8. Antifungal activity of Artemisia annua endophyte cultures against phytopathogenic fungi.

    PubMed

    Liu, C H; Zou, W X; Lu, H; Tan, R X

    2001-07-12

    Artemisia annua, well recognized for its production of antimalarial drug artemisinin, is seldom attacked by any of phytopathogenic fungi, which could be partially associated with the presence of endophytes. Present investigation is aiming at disclosing whether the endophytes inside A. annua produce antifungal substances. A total of 39 endophytes were isolated and fermented, and the ferment broth was evaluated in vitro for the antifungal activity against crop-threatening fungi Gaeumannomyces graminis var. tritici, Rhizoctonia cerealis, Helminthosporium sativum, Fusarium graminearum, Gerlachia nivalis and Phytophthora capsici. These plant pathogens are still causing wheat take-all, sharp eyespot, common rot, scab, snow mould, and pepper phytophthora blight, respectively. Out of 39 endophytes investigated, 21 can produce in vitro substances that are inhibitory to all or a few of the tested phytopathogens whereas the rest yielded nothing active. Moreover, the most active broth of endophyte IV403 was extracted with EtOAc and n-butanol, and comparisons of the antifungal activity of the extracts indicated that the major active metabolites were EtOAc-extractable. PMID:11434973

  9. Identification and characterization of the antifungal substances of a novel Streptomyces cavourensis NA4.

    PubMed

    Pan, Hua-Qi; Yu, Su-Ya; Song, Chun-Feng; Wang, Nan; Hua, Hui-Ming; Hu, Jiang-Chun; Wang, Shu-Jin

    2015-03-01

    A new actinomycete strain NA4 was isolated from a deep-sea sediment collected from the South China Sea and showed promising antifungal activities against soilborne fungal pathogens. It was identified as Streptomyces cavourensis by morphological, physiological, and phylogenetic analyses based on its 16S rRNA gene sequence. The main antifungal components were isolated and identified from the fermentation culture as bafilomycins B1 and C1. These compounds exhibited significant antifungal activities and a broad antifungal spectrum. The results suggest that the Streptomyces cavourensis NA4 and bafilomycins B1 and C1 could be used as potential biocontrol agents for soilborne fungal diseases of plants. PMID:25269816

  10. 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

  11. Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

    PubMed

    Delarze, Eric; Sanglard, Dominique

    2015-11-01

    A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments. PMID:26690338

  12. Antifungal susceptibility patterns of a global collection of fungal isolates: results of the SENTRY Antifungal Surveillance Program (2013).

    PubMed

    Castanheira, Mariana; Messer, Shawn A; Rhomberg, Paul R; Pfaller, Michael A

    2016-06-01

    Among 1846 fungal clinical isolates from 31 countries, echinocandin resistance in Candida spp. ranged from 0.0% to 2.8% (highest for anidulafungin versus Candida glabrata), and fluconazole resistance was noted among 11.9% and 11.6% of the C. glabrata and Candida tropicalis, respectively. Two isolates of Aspergillus fumigatus displayed elevated MICs for itraconazole and carried cyp51a mutations encoding TR34 L98H. All Cryptococcus neoformans had azole MIC values below epidemiological cutoff values. The increasing resistance among certain species and more frequent reports of breakthrough infections in patients undergoing antifungal therapy highlights the importance of antifungal surveillance to guide therapy for patients with invasive fungal infections. PMID:27061369

  13. Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates

    PubMed Central

    Andersen, Kari-Mette; Kristoffersen, Anne Karin; Ingebretsen, André; Vikholt, Katharina Johnsen; Örtengren, Ulf Thore; Olsen, Ingar; Enersen, Morten; Gaustad, Peter

    2016-01-01

    Background Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections. Objectives To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK®2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility. Design A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK®2) and mass spectrometry (MALDI–TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests®. Results Using VITEK®2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L. Conclusions Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high MICs to fluconazole and flucytosine. MALDI-TOF was more definitive than VITEK®2 for C. glabrata identification. PMID:26861194

  14. Glycosidic activities of Candida albicans after action of vegetable latex saps (natural antifungals) and isoconazole (synthetic antifungal).

    PubMed

    Giordani, R; Moulin-Traffort, J; Régli, P

    1991-01-01

    Glycosidic activities have been examined in Candida albicans grown on medium culture containing latex sap (natural antifungal) or isoconazole (synthetic antifungal). The different types of utilized latex sap were those of Lactuca sativa (latex exuded from articulated laticifers) and Asclepias curassavica (latex flowing from non-articulated laticifers). The same enzyme assays were performed on C. albicans grown without antifungal compounds. Except for alpha-arabinosidase, all glycosidase activities were increased when C. albicans was grown in medium supplemented with L. sativa latex sap. The most stimulated activities were those of beta-fucosidase, alpha-galactosidase, alpha- and beta-glucosidase, alpha- and beta-mannosidase, acetyl-beta-glucosaminidase. The presence of A. curassavica latex sap in culture medium produced similar results: the most stimulated activities were those of alpha-mannosidase, alpha-galactosidase, acetyl-beta-glucosaminidase and beta-fucosidase. Electron microscope observations suggested a correlation between this stimulation of glycosidic activities and the fungal cell wall breakdown. For comparison the presence of isoconazole in culture medium yields no increase in glycosidic activities and no ultrastructural modification of fungal cell wall. The mode of action of latex saps in cell wall breakdown is discussed. PMID:1922192

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

    PubMed

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

    2014-05-01

    The past decades have witnessed a dramatic increase in invasive fungal infections, especially candidiasis. Despite the development of more effective new antifungal agents, fluconazole (FLC) is still widely used in the clinic because of its efficacy and low toxicity. However, as the number of patients treated with FLC has increased, FLC-resistant Candida albicans isolates emerge more frequently. In addition, biofilm-associated infections are commonly encountered and their resistance poses a great challenge to antifungal treatment. Various approaches have been proposed to increase the susceptibility of C. albicans to FLC in order to cope with treatment failures, among which is the combination of FLC with different classes of non-antifungal agents such as antibacterials, calcineurin inhibitors, heat shock protein 90 inhibitors, calcium homeostasis regulators and traditional Chinese medicine drugs. Interestingly, many of these combinations showed synergistic effects against C. albicans, especially resistant strains. The main mechanisms of these synergistic effects appear to be increasing the permeability of the membrane, reducing the efflux of antifungal drugs, interfering with intracellular ion homeostasis, inhibiting the activity of proteins and enzymes required for fungal survival, and inhibiting biofilm formation. These modes of action and the antifungal mechanisms of various compounds referenced in this paper highlight the idea that the reversal of fungal resistance can be achieved through various mechanisms. Studies examining drug interactions will hopefully provide new approaches against antifungal drug resistance as well as insight into antifungal agent discovery. PMID:24503221

  16. 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.

  17. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ..., entitled ``Protection of Children from Environmental Health Risks and Safety Risks'' (62 FR 19885, April 23... Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers... . II. Summary of Petitioned-For Tolerance In the Federal Register of May 23, 2012 (Volume 77, FR...

  18. 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)....

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

    PubMed

    Ross, Jeffrey A; Blackman, Carl F; Thai, Sheau-Fung; Li, Zhiguang; Kohan, Michael; Jones, Carlton P; Chen, Tao

    2010-04-01

    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 tumorigenicity, we analyzed the microRNA expression levels in control and conazole-treated mice after 90 d of administration in feed. MicroRNAs (miRNAs) are small noncoding RNAs composed of approximately 19-24 nucleotides in length, and have been shown to interact with mRNA (usually 3' UTR) to suppress its expression. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Groups of mice were fed either control diet or diet containing 1800 ppm triadimefon, 2500 ppm propiconazole, or 2000 ppm myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the significance analysis of microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q < or = 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the nontumorigenic conazole. A group of 19 miRNAs was identified whose expression was significantly altered in both triadimefon- and propiconazole-treated animals but not in myclobutanil-treated animals. All but one of the altered miRNAs were downregulated compared to controls. This pattern of altered miRNA expression may represent a signature for tumorigenic conazole exposure in mouse liver after 90 d of treatment. PMID:20175128

  20. 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 ...

  1. Some Antifungal Properties of Sorbic Acid Extracted from Berries of Rowan (Sorbus Aucuparia).

    ERIC Educational Resources Information Center

    Brunner, Ulrich

    1985-01-01

    The food preservative sorbic acid can be extracted from Eurasian mountain ash berries (commercially available) and used to show antifungal properties in microbiological investigations. Techniques for extraction, purification, ultraviolet analysis, and experiments displaying antifungal activity are described. A systematic search for similar…

  2. 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 ...

  3. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii.

    PubMed Central

    Walsh, T J; Peter, J; McGough, D A; Fothergill, A W; Rinaldi, M G; Pizzo, P A

    1995-01-01

    In order to develop new approaches to treatment of infections due to Pseudallescheria boydii, the in vitro antifungal activity of amphotericin B alone and in combination with miconazole, itraconazole, and fluconazole was studied. Combinations of amphotericin B and antifungal azoles were synergistic, additive, or indifferent in their interaction against P. boydii. Antagonism was not observed. PMID:7574531

  6. 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...

  7. Development of a novel in vitro onychomycosis model for the evaluation of topical antifungal activity.

    PubMed

    Sleven, Reindert; Lanckacker, Ellen; Boulet, Gaëlle; Delputte, Peter; Maes, Louis; Cos, Paul

    2015-05-01

    A novel in vitro onychomycosis model was developed to easily predict the topical activity potential of novel antifungal drugs. The model encompasses drug activity and diffusion through bovine hoof slices in a single experimental set-up. Results correspond well with the antifungal susceptibility assay and Franz cell diffusion test. PMID:25772040

  8. Heterologous expression of new antifungal chitinase from wheat.

    PubMed

    Singh, Arpita; Kirubakaran, S Isaac; Sakthivel, N

    2007-11-01

    Chitinases (EC 3.2.1.14) have been grouped into seven classes (class I-VII) on the basis of their structural properties. Chitinases expressed during plant-microbe interaction are involved in defense responses of host plant against pathogens. In the present investigation, chitinase gene from wheat has been subcloned and overexpressed in Escherichia coli BL-21 (DE3). Molecular phylogeny analyses of wheat chitinase indicated that it belongs to an acidic form of class VII chitinase (glycosyl hydrolase family 19) and shows 77% identity with other wheat chitinase of class IV and low level identity to other plant chitinases. The three-dimensional structural model of wheat chitinase showed the presence of 10 alpha-helices, 3 beta-strands, 21 loop turns and the presence of 6 cysteine residues that are responsible for the formation of 3 disulphide bridges. The active site residues (Glu94 and Glu103) may be suggested for its antifungal activity. Expression of chitinase (33 kDa) was confirmed by SDS-PAGE and Western hybridization analyses. The yield of purified chitinase was 20 mg/L with chitinase activity of 1.9 U/mg. Purified chitinase exerted a broad-spectrum antifungal activity against Colletotrichum falcatum (red rot of sugarcane) Pestalotia theae (leaf spot of tea), Rhizoctonia solani (sheath blight of rice), Sarocladium oryzae (sheath rot of rice) Alternaria sp. (grain discoloration of rice) and Fusarium sp. (scab of rye). Due to its innate antifungal potential wheat chitinase can be used to enhance fungal-resistance in crop plants. PMID:17697785

  9. 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 μm) 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

  10. 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.

  11. Characterization of a new antifungal lipid transfer protein from wheat.

    PubMed

    Kirubakaran, S Isaac; Begum, S Mubarak; Ulaganathan, K; Sakthivel, N

    2008-10-01

    Lipid transfer proteins (LTPs) are members of the family of pathogenesis-related proteins (PR-14) that are believed to be involved in plant defense responses. In this study, a novel gene Ltp 3F1 encoding an antifungal protein from wheat (Sumai 3) was subcloned, overexpressed in Escherichia coli BL-21 (DE3) and enriched using ammonium sulfate fractionation followed by gel permeation chromatography. Molecular phylogeny analyses of wheat Ltp 3F1 gene showed a strong identity to other plant LTPs. Predicted three-dimensional structural model showed the presence of 6 alpha-helices and 9 loop turns. The active site catalytic residues Gly30, Pro50, Ala52 and Cys55 may be suggested for catalyzing the reaction involved in lipid binding. SDS-PAGE analysis confirmed the production of recombinant fusion protein. The LTP fusion protein exhibited a broad-spectrum antifungal activity against Alternaria sp., Rhizoctonia solani, Curvularia lunata, Bipolaris oryzae, Cylindrocladium scoparium, Botrytis cinerea and Sarocladium oryzae. Gene cassette with cyanamide hydratase (cah) marker and Ltp 3F1 gene was constructed for genetic transformation in tobacco. Efficient regeneration was achieved in selective media amended with cyanamide. Transgenic plants with normal phenotype were obtained. Results of PCR and Southern, Northern and Western hybridization analyses confirmed the integration and expression of genes in transgenic plants. Experiments with detached leaves from transgenic tobacco expressing Ltp 3F1 gene showed fungal resistance. Due to the innate potential of broad-spectrum antifungal activity, wheat Ltp 3F1 gene can be used to enhance resistance against fungi in crop plants. PMID:18595724

  12. 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 [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/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 [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/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

  13. New sources and antifungal activity of sesquiterpene lactones.

    PubMed

    Barrero, A F; Oltra, J E; Alvarez, M; Raslan, D S; Sade, D A; Akssira, M

    2000-02-01

    In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones. PMID:11449472

  14. Antifungal activity of the alkaloids from Eschscholzia californica.

    PubMed

    Singh, S; Jain, L; Pandey, M B; Singh, U P; Pandey, V B

    2009-01-01

    The isoquinoline alkaloids hunnemanine and norsanguinarine have been isolated from methanolic extract of the whole plant of Eschscholzia californica. These two alkaloids were checked for their antifungal activity against phytopathogenic fungi Alternaria melongenae, A. brassicola, A. brassicae, Curvularia lunata, C. maculans, Helminthosporium pennisetti, H. oryzae, H. turcicum, Fusarium undum and F. lini. Hunnemanine exhibited 100 % inhibition of spore germination of A. brassicae, H. pennisetti and F. lini at 1000 ppm whereas norsanguinarine exhibited 100 % inhibition of A. brassicicola and C. maculans at this concentration. PMID:19649736

  15. [Pharmaceutical significance of Allium sativum L. 4. Antifungal effects].

    PubMed

    Sovová, M; Sova, P

    2003-03-01

    The recent decades saw an increase in the number of systemic fungal diseases and improvements in the identification of their causative agents. There has been an intensive search for new drugs which would be more effective and less toxic than those already in use. From this aspect, attention has been paid also to garlic--its extracts and individual components, i.e., allicin, ajoen, polysulfides, essential oil. New experimental knowledge confirms a significant antifungal activity of sulfurous compounds of garlic. The paper also mentions a possible use of employing garlic extracts or essential oils in food industry as an alternative way of protection of foodstuffs from contamination with fungi. PMID:12754928

  16. 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 4α-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 14α-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

  17. A radish seed antifungal peptide with a high amyloid fibril-forming propensity.

    PubMed

    Garvey, Megan; Meehan, Sarah; Gras, Sally L; Schirra, Horst J; Craik, David J; Van der Weerden, Nicole L; Anderson, Marilyn A; Gerrard, Juliet A; Carver, John A

    2013-08-01

    The amyloid fibril-forming ability of two closely related antifungal and antimicrobial peptides derived from plant defensin proteins has been investigated. As assessed by sequence analysis, thioflavin T binding, transmission electron microscopy, atomic force microscopy and X-ray fiber diffraction, a 19 amino acid fragment from the C-terminal region of Raphanus sativus antifungal protein, known as RsAFP-19, is highly amyloidogenic. Further, its fibrillar morphology can be altered by externally controlled conditions. Freezing and thawing led to amyloid fibril formation which was accompanied by loss of RsAFP-19 antifungal activity. A second, closely related antifungal peptide displayed no fibril-forming capacity. It is concluded that while fibril formation is not associated with the antifungal properties of these peptides, the peptide RsAFP-19 is of potential use as a controllable, highly amyloidogenic small peptide for investigating the structure of amyloid fibrils and their mechanism of formation. PMID:23665069

  18. Correlation of antifungal susceptibility and molecular type within the Cryptococcus neoformans/C. gattii species complex.

    PubMed

    Trilles, Luciana; Meyer, Wieland; Wanke, Bodo; Guarro, Josep; Lazéra, Marcia

    2012-04-01

    Members of the Cryptococcus neoformans/C. gattii species complex are grouped into eight molecular types, differing in their epidemiology, disease severity and geographic range. Recent in vitro antifungal susceptibility studies of isolates of the complex revealed contradictory results. The objective of the present study was to assess if this variation is random or correlates with different molecular types by testing the in vitro antifungal susceptibility of 18 C. neoformans (VNI), 11 C. gattii (VGI) and 38 C. gattii (VGII) strains from Brazil to eight antifungal drugs using the CLSI microdilution method. We herein report that the molecular type VGII is the least susceptible genotype, followed by VGI and VNI. This indicates a clear correlation between antifungal susceptibilities and genotypes of the causative cryptococcosis agents, emphasizing the importance of determining the molecular type as part of the clinical diagnostic process to enable an informed decision as to the most appropriate antifungal treatment. PMID:21859388

  19. Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014

    PubMed Central

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

    2012-01-01

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

  20. An overview about the medical use of antifungals in Portugal in the last years.

    PubMed

    Manuel da S Azevedo, Maria; Cruz, Luisa; Pina-Vaz, Cidália; Gonçalves-Rodrigues, Acácio

    2016-05-01

    Despite the introduction of new antifungal agents, the frequency of invasive and mucocutaneous fungal infections as well as resistance to antifungal drugs continues to increase. Over 300 million persons are infected annually with fungi. Resistance to antimicrobials is one of today's major health threats. Can the possible causes of fungal antimicrobial resistance be understood and prevented to minimize risks to public health. We provide an overview of antifungal drug use in European countries, particularly Portugal. We reviewed prescriptions for and over-the-counter sales (OTC) of azoles in Portuguese pharmacies and in alternative shops. We conclude that in Portugal, azole antifungal sales, as well as medical prescribed azoles are very high. The Portuguese population consumes more antifungal drugs per capita than others in Europe. PMID:26865319

  1. Antifungal activity and mode of action of silver nano-particles on Candida albicans.

    PubMed

    Kim, Keuk-Jun; Sung, Woo Sang; Suh, Bo Kyoung; Moon, Seok-Ki; Choi, Jong-Soo; Kim, Jong Guk; Lee, Dong Gun

    2009-04-01

    In this study, the antifungal effects of silver nano-particles (nano-Ag) and their mode of action were investigated. Nano-Ag showed antifungal effects on fungi tested with low hemolytic effects against human erythrocytes. To elucidate the antifungal mode of action of nano-Ag, flow cytometry analysis, a glucose-release test, transmission electron microscopy (TEM) and the change in membrane dynamics using 1,6-diphenyl-1,3,5-hexatriene (DPH), as a plasma membrane probe, were performed with Candida albicans. The results suggest nano-Ag may exert an antifungal activity by disrupting the structure of the cell membrane and inhibiting the normal budding process due to the destruction of the membrane integrity. The present study indicates nano-Ag has considerable antifungal activity, deserving further investigation for clinical applications. PMID:18769871

  2. The effects of Paenibacillus polymyxa E681 on antifungal and crack remediation of cement paste.

    PubMed

    Park, Sung-Jin; Park, Seung-Hwan; Ghim, Sa-Youl

    2014-10-01

    This study investigated the antifungal effects of cement paste containing Paenibacillus polymyxa E681 against Aspergillus niger, a deleterious fungus commonly found in cement buildings and structures. To test the antifungal effects, cement paste containing P. polymyxa E681 was neutralized by CO2 gas, and the fungal growth inhibition was examined according to the clear zone around the cement specimen. In addition to the antifungal effects of the cement paste added with bacteria, calcium crystal precipitation of P. polymyxa E681 was examined by qualitative and quantitative analyses. The cement paste containing P. polymyxa E681 showed strong antifungal effects but fusA mutant (deficient in fusaricidin synthesis) showed no antifungal activity. Crack sealing of the cement paste treated with P. polymyxa E681 was captured by light microscope showed fungal growth inhibition and crack repairing in cement paste. PMID:24824950

  3. Analysis of the mutations induced by conazole fungicides in vivo.

    PubMed

    Ross, Jeffrey A; Leavitt, Sharon A

    2010-05-01

    The mouse liver tumorigenic conazole fungicides 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 non-tumorigenic conazole myclobutanil was not mutagenic. DNA sequencing of the mutants recovered from each treatment group as well as from animals receiving control diet was conducted to gain additional insight into the mode of action by which tumorigenic conazoles induce mutations. Relative dinucleotide mutabilities (RDMs) were calculated for each possible dinucleotide in each treatment group and then examined by multivariate statistical analysis techniques. Unsupervised hierarchical clustering analysis of RDM values segregated two independent control groups together, along with the non-tumorigen myclobutanil. The two tumorigenic conazoles clustered together in a distinct grouping. Partitioning around mediods of RDM values into two clusters also groups the triadimefon and propiconazole together in one cluster and the two control groups and myclobutanil together in a second cluster. Principal component analysis of these results identifies two components that account for 88.3% of the variability in the points. Taken together, these results are consistent with the hypothesis that propiconazole- and triadimefon-induced mutations do not represent clonal expansion of background mutations and support the hypothesis that they arise from the accumulation of reactive electrophilic metabolic intermediates within the liver in vivo. PMID:20064898

  4. 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

  5. Differential antifungal and calcium channel-blocking activity among structurally related plant defensins.

    PubMed

    Spelbrink, Robert G; Dilmac, Nejmi; Allen, Aron; Smith, Thomas J; Shah, Dilip M; Hockerman, Gregory H

    2004-08-01

    Plant defensins are a family of small Cys-rich antifungal proteins that play important roles in plant defense against invading fungi. Structures of several plant defensins share a Cys-stabilized alpha/beta-motif. Structural determinants in plant defensins that govern their antifungal activity and the mechanisms by which they inhibit fungal growth remain unclear. Alfalfa (Medicago sativa) seed defensin, MsDef1, strongly inhibits the growth of Fusarium graminearum in vitro, and its antifungal activity is markedly reduced in the presence of Ca(2+). By contrast, MtDef2 from Medicago truncatula, which shares 65% amino acid sequence identity with MsDef1, lacks antifungal activity against F. graminearum. Characterization of the in vitro antifungal activity of the chimeras containing portions of the MsDef1 and MtDef2 proteins shows that the major determinants of antifungal activity reside in the carboxy-terminal region (amino acids 31-45) of MsDef1. We further define the active site by demonstrating that the Arg at position 38 of MsDef1 is critical for its antifungal activity. Furthermore, we have found for the first time, to our knowledge, that MsDef1 blocks the mammalian L-type Ca(2+) channel in a manner akin to a virally encoded and structurally unrelated antifungal toxin KP4 from Ustilago maydis, whereas structurally similar MtDef2 and the radish (Raphanus sativus) seed defensin Rs-AFP2 fail to block the L-type Ca(2+) channel. From these results, we speculate that the two unrelated antifungal proteins, KP4 and MsDef1, have evolutionarily converged upon the same molecular target, whereas the two structurally related antifungal plant defensins, MtDef2 and Rs-AFP2, have diverged to attack different targets in fungi. PMID:15299136

  6. Antifungal agents for secondary prophylaxis based on response to initial antifungal therapy in allogeneic hematopoietic stem cell transplant recipients with prior pulmonary aspergillosis.

    PubMed

    Liu, Qifa; Lin, Ren; Sun, Jing; Xiao, Yang; Nie, Danian; Zhang, Yu; Huang, Fen; Fan, Zhiping; Zhou, Hongsheng; Jiang, Qianli; Zhang, Fuhua; Zhai, Xiao; Xu, Dan; Wei, Yongqiang; Song, Jiayin; Li, Yiqing; Feng, Ru

    2014-08-01

    We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P=.675) nor between patients with active and stable IPA (P= .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3%4.5% and 24.7%4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation. PMID:24769013

  7. 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... 0.70 Milk 0.2 Okra 4.0 Papaya 3.0 Peppermint, tops 3.0 Plum, prune, dried 8.0 Poultry, fat...

  8. 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... 0.70 Milk 0.2 Okra 4.0 Papaya 3.0 Peppermint, tops 3.0 Plum, prune, dried 8.0 Poultry, fat...

  9. 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... 0.70 Milk 0.2 Okra 4.0 Papaya 3.0 Peppermint, tops 3.0 Plum, prune, dried 8.0 Poultry, fat...

  10. 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... 0.70 Milk 0.2 Okra 4.0 Papaya 3.0 Peppermint, tops 3.0 Plum, prune, dried 8.0 Poultry, fat...

  11. 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... 0.70 Milk 0.2 Okra 4.0 Papaya 3.0 Peppermint, tops 3.0 Plum, prune, dried 8.0 Poultry, fat...

  12. 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

  13. Cryptococcus laurentii biofilms: structure, development and antifungal drug resistance.

    PubMed

    Ajesh, K; Sreejith, K

    2012-12-01

    A great number of fungal infections are related to biofilm formation on inert or biological surfaces, which are recalcitrant to most treatments and cause human mortality. Cryptococcus laurentii has been diagnosed as the aetiological pathogen able to cause human infections mainly in immunosuppressed patients and the spectrum of clinical manifestations ranges from skin lesions to fungaemia. The effect of temperature, pH and surface preconditioning on C. laurentii biofilm formation was determined by 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay. Scanning electron microscopic (SEM) analysis of C. laurentii biofilms demonstrated surface topographies of profuse growth and dense colonization with extensive polymeric substances around the cells. In this study, we determined the activity of amphotericin B, itraconazole and fluconazole against C. laurentii free-living cells and biofilms. The activity of antifungals tested was greater against free-living cells, but sessile cells fell into the resistant range for these antifungal agents. Extracellular polymeric substances (EPS), comprising the matrix of C. laurentii biofilms, were isolated by ultrasonication. Fourier transform infrared spectroscopy (FT-IR) was performed with ethanol-precipitated and dried samples. Also, the multielement analysis of the EPS was performed by inductively coupled plasma optical emission spectroscopy (ICP-OES). PMID:22936102

  14. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES

    PubMed Central

    BIASI-GARBIN, Renata Perugini; DEMITTO, Fernanda de Oliveira; do AMARAL, Renata Claro Ribeiro; FERREIRA, Magda Rhayanny Assunção; SOARES, Luiz Alberto Lira; SVIDZINSKI, Terezinha Inez Estivalet; BAEZA, Lilian Cristiane; YAMADA-OGATTA, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytesATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  15. Antifungal activity of lectins against yeast of vaginal secretion

    PubMed Central

    Gomes, Bruno Severo; Siqueira, Ana Beatriz Sotero; de Cássia Carvalho Maia, Rita; Giampaoli, Viviana; Teixeira, Edson Holanda; Arruda, Francisco Vassiliepe Sousa; do Nascimento, Kyria Santiago; de Lima, Adriana Nunes; Souza-Motta, Cristina Maria; Cavada, Benildo Sousa; Porto, Ana Lúcia Figueiredo

    2012-01-01

    Lectins are carbohydrate-binding proteins of non-imune origin. This group of proteins is distributed widely in nature and they have been found in viruses, microorganisms, plants and animals. Lectins of plants have been isolated and characterized according to their chemical, physical-chemical, structural and biological properties. Among their biological activities, we can stress its fungicidal action. It has been previously described the effect of the lectins Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the growth of yeasts isolated from vaginal secretions. In the present work the experiments were carried out in microtiter plates and the results interpreted by both methods: visual observations and a microplate reader at 530nm. The lectin concentrations varied from 0.5 to 256μg/mL, and the inoculum was established between 65-70% of trammitance. All yeast samples isolated from vaginal secretion were evaluated taxonomically, where were observed macroscopic and microscopic characteristics to each species. The LSL lectin did not demonstrate any antifungal activity to any isolate studied. The other lectins DRL, ConBr and DvioL, showed antifungal potential against yeast isolated from vaginal secretion. These findings offering offer a promising field of investigation to develop new therapeutic strategies against vaginal yeast infections, collaborating to improve women's health. PMID:24031889

  16. Glycerol Enhances the Antifungal Activity of Dairy Propionibacteria

    PubMed Central

    Lind, Helena; Broberg, Anders; Jacobsson, Karin; Jonsson, Hans; Schnürer, Johan

    2010-01-01

    Dairy propionibacteria are widely used in starter cultures for Swiss type cheese. These bacteria can ferment glucose, lactic acid, and glycerol into propionic acid, acetic acid, and carbon dioxide. This research examined the antifungal effect of dairy propionibacteria when glycerol was used as carbon source for bacterial growth. Five type strains of propionibacteria were tested against the yeast Rhodotorula mucilaginosa and the molds Penicillium commune and Penicillium roqueforti. The conversion of 13C glycerol by Propionibacterium jensenii was followed with nuclear magnetic resonance. In a dual culture assay, the degree of inhibition of the molds was strongly enhanced by an increase in glycerol concentrations, while the yeast was less affected. In broth cultures, decreased pH in glycerol medium was probably responsible for the complete inhibition of the indicator fungi. NMR spectra of the glycerol conversion confirmed that propionic acid was the dominant metabolite. Based on the results obtained, the increased antifungal effect seen by glycerol addition to cultures of propionibacteria is due to the production of propionic acid and pH reduction of the medium. PMID:21331381

  17. Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests.

    PubMed Central

    Espinel-Ingroff, A; Kish, C W; Kerkering, T M; Fromtling, R A; Bartizal, K; Galgiani, J N; Villareal, K; Pfaller, M A; Gerarden, T; Rinaldi, M G

    1992-01-01

    A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories. MICs of amphotericin B, fluconazole, flucytosine, and ketoconazole were determined in all five centers against 95 coded isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata. A standard protocol with the following National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Susceptibility Testing recommendations was used: an inoculum standardized by spectrophotometer, buffered (RPMI 1640) medium (pH 7.0), incubation at 35 degrees C, and an additive drug dilution procedure. Two inoculum sizes were tested (1 x 10(4) to 5 x 10(3) to 2.5 x 10(3) CFU/ml) and three scoring criteria were evaluated for MIC endpoint determinations, which were scored as 0 (optically clear), < or = 1 (slightly hazy turbidity), and < or = 2 (prominent decrease in turbidity compared with that of the growth control). Overall intra- and interlaboratory reproducibility was optimal with the low-density inoculum, the second-day readings, and MICs scored as either 1 or 2. The microdilution MICs demonstrated interlaboratory agreement with most of the four drugs higher than or similar to that of the macrodilution MICs. In general, there was good interlaboratory agreement with amphotericin B, fluconazole, and flucytosine; ketoconazole gave more variable results. PMID:1452697

  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. Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris.

    PubMed

    Wong, Jack H; Ng, Tzi Bun; Wang, Hexiang; Sze, Stephen Cho Wing; Zhang, Kalin Yanbo; Li, Qi; Lu, Xiaoxu

    2011-03-15

    Cordymin, an antifungal peptide with a molecular mass of 10,906 Da and an N-terminal amino acid sequence distinct from those of previously reported proteins, was purified from the medicinal mushroom Cordyceps militaris. The isolation protocol comprised ion exchange chromatography of the aqueous extract on SP-Sepharose and Mono S and gel filtration on Superdex 75 by a fast protein liquid chromatography system. Cordymin was adsorbed on both cation exchangers. The peptide inhibited mycelial growth in Bipolaris maydis, Mycosphaerella arachidicola, Rhizoctonia solani and Candida albicans with an IC(50) of 50 ?M, 10 ?M, 80 ?M, and 0.75 mM, respectively. However, there was no effect on Aspergillus fumigatus, Fusarium oxysporum and Valsa mali when tested up to 2 mM. The antifungal activity of the peptide was stable up to 100C and in the pH range 6-13, and unaffected by 10 mM Zn(2+) and 10 mM Mg(2+). Cordymin inhibited HIV-1 reverse transcriptase with an IC(50) of 55 ?M. Cordymin displayed antiproliferative activity toward breast cancer cells (MCF-7) but there was no effect on colon cancer cells (HT-29). There was no mitogenic activity toward mouse spleen cells and no nitric oxide inducing activity toward mouse macrophages when tested up to 1 mM. PMID:20739167

  20. Antifungal and insecticidal activity of two Juniperus essential oils.

    PubMed

    Wedge, David E; Tabanca, Nurhayat; Sampson, Blair J; Werle, Christopher; Demirci, Betul; Baser, K Husnu Can; Nan, Peng; Duan, Jia; Liu, Zhijun

    2009-01-01

    Essential oils of two Tibetan Junipers Juniperus saltuaria and J. squamata var. fargesii (Cupressaceae) were obtained by distilling dried leaves and branches using a Clevenger apparatus. Sixty-seven compounds from J. saltuaria and 58 from J. squamata var. fargesii were identified by gas chromatography-mass spectrometry (GC-MS). Both essential oils contained similar ratios of four abundant monoterpenoids: 44 and 35% sabinene, 13 and 9% elemol, 8 and 7% terpinen-4-ol, and 4 and 17% alpha-pinene, respectively. These oils had antifungal activity based on a direct bioautography assay of Colletotrichum acutatum, C. fragariae, and C. gloeosporioides, and insecticidal activity based on serial-time mortality bioassay of azalea lace bugs, Stephanitis pyrioides. Antifungal activity of Juniperus oils was weak when compared with commercial fungicides such as benomyl and captan. Whole Juniperus oils at quarter the dosage used against Colletotrichum species were more insecticidal than 10 mg/mL malathion, killing > or =70-90% adult lace bugs after 4 hours of exposure. Rf values of 0.18 for J. saltuaria oil and 0.19 for J. squamata oil indicated lipophilic monoterpenes which were the putative sources of biological activity. PMID:19370889

  1. 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

  2. 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

  3. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES.

    PubMed

    Biasi-Garbin, Renata Perugini; Demitto, Fernanda de Oliveira; Amaral, Renata Claro Ribeiro do; Ferreira, Magda Rhayanny Assunção; Soares, Luiz Alberto Lira; Svidzinski, Terezinha Inez Estivalet; Baeza, Lilian Cristiane; Yamada-Ogatta, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytesATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  4. Chemical composition, antifungal and insecticidal activities of Hedychium essential oils.

    PubMed

    Sakhanokho, Hamidou F; Sampson, Blair J; Tabanca, Nurhayat; Wedge, David E; Demirci, Betul; Baser, Kemal Husnu Can; Bernier, Ulrich R; Tsikolia, Maia; Agramonte, Natasha M; Becnel, James J; Chen, Jian; Rajasekaran, Kanniah; Spiers, James M

    2013-01-01

    The antimicrobial properties of essential oils have been documented, and their use as "biocides" is gaining popularity. The aims of this study were to analyze the chemical composition and assess the biological activities of Hedychium essential oils. Oils from 19 Hedychium species and cultivars were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antifungal and insecticidal activities of these oils were tested against Colletotrichum acutatum, C. fragariae, and C. gloeosporioides, and three insects, the azalea lace bug (Stephanitis pyrioides), the yellow fever mosquito (Aedes aegypti), and the red imported fire ant (Solenopsis invicta). Hedychium oils were rich in monoterpenes and sesquiterpenes, especially 1,8-cineole (0.1%-42%), linalool (<0.1%-56%), a-pinene (3%-17%), b-pinene (4%-31%), and (E)-nerolidol (0.1%-20%). Hedychium oils had no antifungal effect on C. gloeosporioides, C. fragariae, and C. acutatum, but most Hedychium oils effectively killed azalea lace bugs. The oils also show promise as an adult mosquito repellent, but they would make rather poor larvicides or adulticides for mosquito control. Hedychium oils acted either as a fire ant repellent or attractant, depending on plant genotype and oil concentration. PMID:23579997

  5. 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

  6. The Antifungal Protein from Aspergillus giganteus Causes Membrane Permeabilization

    PubMed Central

    Theis, T.; Wedde, M.; Meyer, V.; Stahl, U.

    2003-01-01

    We investigated the inhibitory effects of the antifungal protein (AFP) from Aspergillus giganteus on the growth of several filamentous fungi. For this purpose, the MICs of AFP were determined and ranged from 0.1 μg/ml for Fusarium oxysporum to 200 μg/ml for Aspergillus nidulans. The antifungal activity of AFP was diminished in the presence of cations. We were able to show that incubation of AFP-sensitive fungi with the protein resulted in membrane permeabilization using an assay based on the uptake of the fluorescent dye SYTOX Green. No permeabilization by AFP could be detected at concentrations below the species-specific MIC. Furthermore, AFP-induced permeabilization could readily be detected after 5 min of incubation. Localization experiments with fluorescein isothiocyanate-labeled AFP and immunofluorescence staining with an AFP-specific antibody supported the observation that the protein interacts with membranes. After treatment of AFP-sensitive fungi with AFP, the protein was localized at the plasma membrane, whereas it was mainly detected inside the cells of AFP-resistant fungi. We conclude from these data that the growth-inhibitory effect of AFP is caused by permeabilization of the fungal membranes. PMID:12543664

  7. Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung

    PubMed Central

    Dutta, Orchi; Kasahara, Shinji; Donnelly, Robert; Du, Peicheng; Rosenfeld, Jeffrey; Leiner, Ingrid; Chen, Chiann-Chyi; Ron, Yacov; Hohl, Tobias M.; Rivera, Amariliz

    2014-01-01

    Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity. First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2+Mo and their derivatives in innate antifungal immunity in the lung. PMID:24586155

  8. Antibacterial and antifungal activities of some Mexican medicinal plants.

    PubMed

    Ruiz-Bustos, E; Velazquez, C; Garibay-Escobar, A; García, Z; Plascencia-Jatomea, M; Cortez-Rocha, M O; Hernandez-Martínez, J; Robles-Zepeda, R E

    2009-12-01

    In Mexico about 4,000 plant species have some medicinal use. The aim of this work was to evaluate the antimicrobial activity of six Mexican medicinal plants against fungi and Gram-positive and Gram-negative bacteria. Methanolic extracts were prepared from the Mexican medicinal plants Amphypteringium adstrigens, Castella tortuosa, Coutarea latiflora, Ibervillea sonorae, Jatropha cuneata, and Selaginella lepidophylla. The antibacterial and antifungal activities of the plants were determined by the broth microdilution method and the radial growth inhibition assay, respectively. All Mexican plants tested showed antimicrobial activity. Among the six plant extracts analyzed, J. cuneata showed the highest growth-inhibitory activity against fungi, Gram-positive and Gram-negative bacteria (J. cuneata > A. adstrigens > C. latiflora > C. tortuosa > I. sonorae approximately S. lepidophylla). Shigella flexneri and Staphylococcus aureus were the most susceptible bacteria to plant extracts. Complete inhibition of S. flexneri growth was observed with J. cuneata methanolic extract at 90 microg/mL. This plant extract also showed the strongest antifungal activity against Fusarium verticillioides and Aspergillus niger. Our data suggest that the medicinal plants tested have important antimicrobial properties. This is the first report describing the antimicrobial activities of several of the Mexican medicinal plants used in this study. PMID:20041800

  9. Streptomyces ansochromogenes Tur-10 produces a substance with antifungal bioactivity.

    PubMed

    Vasconcelos, N M; Fontes, J M; Lins, M R C R; Bernardo, G R B; Arajo, J M; Lima, G M S

    2015-01-01

    The increased incidence of fungal infections and the development of drug resistance have led to the search for microorganisms capable of producing bioactive metabolites with antifungal activity. Among these microorganisms, Streptomyces spp are distinguished mainly owing to their potential to secrete bioactive molecules. The aim of this study was to evaluate the production of secondary metabolites by Streptomyces sp TUR-10 against 12 fungal clinical isolates (yeast and filamentous fungi). In the preliminary screening, Streptomyces sp TUR-10 showed activity against 75% of the clinical isolates, and was selected for fermentation. In this assay, we tested three different media (MPE, M1, and ISP-4) for 96 h at pH 7.0 and 30C for the production of bioactive metabolites. Increased production of bioactive compounds was observed when using the MPE medium for 48 h, with good activity against Candida pelliculosa. The minimum inhibitory concentration showed significant antifungal activity values ranging from 15.6 to 250 ?g/mL. The actinobacterium was characterized by 16S rRNA analysis and the pattern suggested that the isolate studied belonged to the species Streptomyces ansochromogenes. The biotechnological potential of this strain was also demonstrated by the detection of the nrps and pks genes. These results indicate the production of secondary metabolites of biotechnological interest by actinobacteria from the rhizosphere, suggesting great potential for further research. PMID:26125739

  10. Novel synergism of two antifungal agents, copiamycin and imidazole.

    PubMed Central

    Uno, J; Shigematsu, M L; Arai, T

    1983-01-01

    Copiamycin, a macrocyclic lactone antifungal antibiotic, was found to potentiate the antifungal effect of imidazole compounds, ketoconazole in particular. The potentiation of two nominally fungistatic agents in vitro was substantiated by a marked reduction of the minimum inhibitory and minimum fungicidal concentrations when the drugs were used in combination. The effectiveness of this synergistic combination was also demonstrated in experimental murine candidosis. Evidence is presented to suggest that this combined effect is due, at least in part, to the ionophoretic property of copiamycin. Whereas amphotericin B induces a marked increase in cellular permeability, this antibiotic does not possess the ionophoretic action of copiamycin, indicating that the enhancement of copiamycin activity and significant reduction of amphotericin B activity by ketoconazole pretreatment can be ascribed not only to changes in membrane permeability of the test organisms, but also to the different action mechanisms of copiamycin and amphotericin B. It is thus plausible that the strong synergism of copiamycin with imidazole compounds is related to the ionophoretic activity of the antibiotic. Further studies on the biochemical mechanism of this synergistic effect are being conducted together with an assessment of the clinical significance of this drug combination. Images PMID:6316846

  11. 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.

  12. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

    PubMed Central

    Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  13. Methylxanthine Inhibit Fungal Chitinases and Exhibit Antifungal Activity

    PubMed Central

    Tsirilakis, Kalliope; Kim, Christy; Vicencio, Alfin G.; Andrade, Christopher; Casadevall, Arturo; Goldman, David L.

    2015-01-01

    Chitinases are necessary for fungal cell wall remodeling and cell replication. Methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. We sought to determine the effects of methylxanthines on fungal chitinases. Fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5–10 mM) resulted in a dose-dependent decrease in this activity. All fungi tested, except for Candida spp., demonstrated growth inhibition in the presence of methylxanthines at a concentration of 10 mM. India ink staining demonstrated impaired budding and decreased cell size for methylxanthine-treated Cryptococcus neoformans. C. neoformans and Aspergillus fumigatus treated with pentoxifylline also exhibited abnormal cell morphology. In addition, pentoxifylline-treated C. neoformans exhibited increased susceptibility to calcofluor and a leaky melanin phenotype consistent with defective cell wall function. Our data suggest that a variety of fungi express chitinases and that methylxanthines have antifungal properties related to their inhibition of fungal chitinases. Our results highlight the potential utility of targeting chitinases in the development of novel antifungal therapies. PMID:21968902

  14. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals.

    PubMed

    Akhtar, Nida; Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  15. Synthesis and antifungal activity of novel sclerotiorin analogues.

    PubMed

    Lin, Long; Mulholland, Nick; Wu, Qiong-You; Beattie, David; Huang, Shao-Wei; Irwin, Dianne; Clough, John; Gu, Yu-Cheng; Yang, Guang-Fu

    2012-05-01

    Sclerotiorin 1, first isolated from Penicillium sclerotiorum, has weak antifungal activity and belongs to the azaphilone-type family of natural products. Several series of sclerotiorin analogues were designed and synthesized with the aim of discovering novel fungicides with improved activity. The syntheses involved two key steps, cycloisomerization and then oxidation, and used a simple and efficient Sonogashira cross-coupling reaction to construct the required functionalized precursor. With sclerotiorin as a control, the activities of the newly synthesized analogues were evaluated against seven fungal pathogens, and several promising candidates (compounds 3a₁, 3d₂, 3e₂, 3f₂ and 3k₂) with greater activity and simpler structures than sclerotiorin were discovered. In addition, preliminary structure-activity relationships were studied, which revealed that not only the chlorine or bromine substituent at the 5-position of the nucleus but also the phenyl group at the 3-position and the substituent pattern on it contributed crucially to the observed antifungal activity. Analogues with a methyl substituent at the 1-position have reduced levels of activity, while those with a free hydroxyl group in place of acetoxy at the quaternary center of the bicyclic ring system retain activity. PMID:22439963

  16. 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; Knøchel, 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

  17. Antifungal treatment in allergic bronchopulmonary aspergillosis with and without cystic fibrosis: a systematic review.

    PubMed

    Moreira, A S; Silva, D; Ferreira, A Reis; Delgado, L

    2014-10-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA. PMID:24809846

  18. 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

  19. Correlation between Antifungal Susceptibilities of Coccidioides immitis In Vitro and Antifungal Treatment with Caspofungin in a Mouse Model

    PubMed Central

    González, Gloria M.; Tijerina, Rolando; Najvar, Laura K.; Bocanegra, Rosie; Luther, Michael; Rinaldi, Michael G.; Graybill, John R.

    2001-01-01

    Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis. In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines. Two C. immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains were used for animal studies. Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers. Mice infected with strain 98-449 (48-h MIC, 8 μg/ml; 48-h MEC, 0.125 μg/ml) showed 100% survival to day 50 when treated with caspofungin at ≥1 mg/kg. Mice infected with strain 98-571 (48-h MIC, 64 μg/ml; 48-h MEC, 0.125 μg/ml) displayed ≥80% survival when the treatment was caspofungin at ≥5 mg/kg. Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate. When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains. A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing. Caspofungin may have a role in the treatment of coccidioidomycosis. PMID:11353637

  20. In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections

    PubMed Central

    Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera

    2014-01-01

    Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737

  1. 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

  2. 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

  3. Update from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance.

    PubMed

    Albataineh, Mohammad T; Sutton, Deanna A; Fothergill, Annette W; Wiederhold, Nathan P

    2016-03-01

    Despite the availability of new diagnostic assays and broad-spectrum antifungal agents, invasive fungal infections remain a significant challenge to clinicians and are associated with marked morbidity and mortality. In addition, the number of etiologic agents of invasive mycoses has increased accompanied by an expansion in the immunocompromised patient populations, and the use of molecular tools for fungal identification and characterization has resulted in the discovery of several cryptic species. This article reviews various methods used to identify fungi and perform antifungal susceptibility testing in the clinical laboratory. Recent developments in antifungal resistance are also discussed. PMID:26739605

  4. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  5. 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 14α-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 14α-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

  6. Endophytic bacteria from banana cultivars and their antifungal activity.

    PubMed

    Souza, A; Cruz, J C; Sousa, N R; Procpio, A R L; Silva, G F

    2014-01-01

    Endophytic microorganisms consist of fungi, bacteria, and actinomycetes that play important roles in the process of plant adaptation to the environment. Currently, the natural associations between microorganisms and plant species are being explored for a large number of biotechnological applications. In this study, 122 endophytic bacteria were isolated from 5 cultivars of Musa spp from the state of Amazonas (Brazil). Four strains were selected because they exhibited antagonistic activities against Fusarium oxysporum f. sp cubense and Colletotrichum guaranicola, with inhibitions ranging from 19 to 30% and 27 to 35%, respectively. Phylogenetic analysis of the 16S rDNA regions of these bacteria with antifungal activity showed that they are phylogenetically related to 3 different species of Bacillus - B. amyloliquefaciens, B. subtilis subsp subtilis, and B. thuringiensis. PMID:25366756

  7. 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

  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. Colorimetric Assay for Antifungal Susceptibility Testing of Aspergillus Species

    PubMed Central

    Meletiadis, Joseph; Mouton, Johan W.; Meis, Jacques F. G. M.; Bouman, Bianca A.; Donnelly, J. Peter; Verweij, Paul E.

    2001-01-01

    A colorimetric assay for antifungal susceptibility testing of Aspergillus species (Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus nidulans, and Aspergillus ustus) is described based on the reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-[(sulphenylamino)carbonyl]-2H-tetrazolium-hydroxide (XTT) in the presence of menadione as an electron-coupling agent. The combination of 200 μg of XTT/ml with 25 μM menadione resulted in a high production of formazan within 2 h of exposure, allowing the detection of hyphae formed by low inocula of 102 CFU/ml after 24 h of incubation. Under these settings, the formazan production correlated linearly with the fungal biomass and less-variable concentration effect curves for amphotericin B and itraconazole were obtained. PMID:11526191

  10. Partial identification of antifungal compounds from Punica granatum peel extracts.

    PubMed

    Glazer, Ira; Masaphy, Segula; Marciano, Prosper; Bar-Ilan, Igal; Holland, Doron; Kerem, Zohar; Amir, Rachel

    2012-05-16

    Aqueous extracts of pomegranate peels were assayed in vitro for their antifungal activity against six rot fungi that cause fruit and vegetable decay during storage. The growth rates of Alternaria alternata , Stemphylium botryosum , and Fusarium spp. were significantly inhibited by the extracts. The growth rates were negatively correlated with the levels of total polyphenolic compounds in the extract and particularly with punicalagins, the major ellagitannins in pomegranate peels. Ellagitannins were also found to be the main compounds in the bioactive fractions using bioautograms, and punicalagins were identified as the main bioactive compounds using chromatographic separation. These results suggest that ellagitannins, and more specifically punicalagins, which are the dominant compounds in pomegranate peels, may be used as a control agent of storage diseases and to reduce the use of synthetic fungicides. PMID:22533815

  11. Leaf oil bodies are subcellular factories producing antifungal oxylipins.

    PubMed

    Shimada, Takashi L; Hara-Nishimura, Ikuko

    2015-06-01

    Oil bodies act as lipid storage compartments in plant cells. In seeds they supply energy for germination and early seedling growth. Oil bodies are also present in the leaves of many vascular plants, but their function in leaves has been poorly understood. Recent studies with oil bodies from senescent Arabidopsis thaliana leaves identified two enzymes, peroxygenase (CLO3) and α-dioxygenase (α-DOX), which together catalyze a coupling reaction to produce an antifungal compound (2-hydroxy-octadecanoic acid) from α-linolenic acid. Leaf oil bodies also have other enzymes including lipoxygenases, phospholipases, and triacylglycerol lipases. Hence, leaf oil bodies might function as intracellular factories to efficiently produce stable compounds via unstable intermediates by concentrating the enzymes and hydrophobic substrates. PMID:26051035

  12. 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

  13. [Chalcones and their heterocyclic analogs as potential antifungal chemotherapeutic agents].

    PubMed

    Opletalová, V; Sedivý, D

    1999-11-01

    Chalcones and their heterocyclic analogues show various biological effects, e.g. anti-inflammatory, antitumour, antibacterial, antituberculous, antiviral, antiprotozoal, gastroprotective, and others. The present review discusses in greater detail the fungistatic and fungicide properties of these compounds and presents also their chemical structures. The mechanism of antifungal effects of chalcones and their analogues has not been investigated in greater detail. Due to the presence of a reactive ketovinyl moiety in the molecule the compounds of this type are able to react with the thiol groups of enzymes. It cannot be excluded that chalcones interfere with the normal function of the membranes of fungi and moulds. Further investigation of chemical, physical, and biological properties of chalcones and their analogues could lead to the elucidation of the mechanism of their action and finding of effective fungicidal and fungistatic agents in this group of organic substances. PMID:10748740

  14. Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

    PubMed Central

    Kouznetsov, Vladímir V.; Zacchino, Susana A.; Sortino, Maximiliano; Vargas Méndez, Leonor Y.; Gupta, Mahabir P.

    2012-01-01

    Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC50 < 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. PMID:23264936

  15. Antifungal activity of alpha-mangostin against Candida albicans.

    PubMed

    Kaomongkolgit, Ruchadaporn; Jamdee, Kusuma; Chaisomboon, Niratcha

    2009-09-01

    This study was conducted to examine the activity of alpha-mangostin against Candida albicans, the most important microorganism implicated in oral candidiasis. Its activity was compared to Clotrimazole and Nystatin. Results showed that alpha-mangostin was effective against C. albicans, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were 1,000 and 2,000 microg/ml, respectively. The C. albicans killing activity of alpha-mangostin was more effective than Clotrimazole and Nystatin. The cytotoxicity of alpha-mangostin was determined and it was found that alpha-mangostin at 4,000 microg/ml was not toxic to human gingival fibroblast for 480 min. The strong antifungal activity and low toxicity of alpha-mangostin make it a promising agent for treatment of oral candidiasis. PMID:19776506

  16. Antifungal activity of silver nanoparticles obtained by green synthesis.

    PubMed

    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

  17. A lectin with antifungal activity from the mussel Crenomytilus grayanus.

    PubMed

    Chikalovets, Irina V; Chernikov, Oleg V; Pivkin, Mikhail V; Molchanova, Valentina I; Litovchenko, Alina P; Li, Wei; Lukyanov, Pavel A

    2015-02-01

    Lectins (carbohydrate-binding proteins) are well known to actively participate in the defense functions of vertebrates and invertebrates where they play an important role in the recognition of foreign particles. In this study, we investigated of in vitro antifungal activity of lectin from the mussel Crenomytilus grayanus (CGL). Enzyme-linked immunosorbent assay indicated that CGL was predominantly detectable in tissues of mantle and to a lesser degree in the tissues of muscle, hepatopancreas, gill and hemocytes. After challenged by Pichia pastoris the level of CGL was upregulated and reached the maximum level at 12 h post challenge and recovered to the original level at 24 h. The lectin was capable of inhibiting the germination of spores and hyphal growth in the fungi. All these results indicated that CGL is involved in the innate immune response in mollusc animals. PMID:25482060

  18. 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

  19. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID:26827629

  20. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species.

    PubMed

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-02-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  1. Which antifungal agent for onychomycosis? A pharmacoeconomic analysis.

    PubMed

    Joish, V N; Armstrong, E P

    2001-01-01

    The incidence of fungal nail infections is increasing and this is possibly because of several factors: better methods of detection, a growing population of immunocompromised patients who have a greater susceptibility to such infections, the increased use of immunosuppressive drugs, the increasing number of elderly people, worldwide travel, and the use of communal bathing facilities. Onychomycosis is a fungal infection of the fingernails and toenails that accounts for about 30% of all superficial fungal infections. It is characterised by nail discoloration, thickening and ultimately destruction of the nail plate. Management of this disease has improved significantly and treatment patterns have dramatically changed in recent years as a result of advances in new treatment options (e.g. oral antifungal agents) and changes in treatment regimens (e.g. pulse therapy). Also, newer drugs for onychomycosis have improved tolerability profiles compared with older agents. The overall costs of treating onychomycosis are substantial, and it has been estimated that direct cost for US Medicare patients with the disease is 43 million US dollars per year (year of costing not available). Pharmacoeconomic studies help in the decision-making process when selecting the most cost-effective antifungal agents to treat onychomycosis. To date there have been a number of national and international economic studies aimed at effectively assessing the efficacy and costs of the treatment options available to cure onychomycosis. The objectives of this paper are to (i) review the published findings regarding the epidemiology of onychomycosis; (ii) summarise the original pharmacoeconomic studies that describe the economic impact of the disease; and (iii) address the impact of the disease on patients' health-related quality of life. PMID:11735669

  2. 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

  3. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species

    PubMed Central

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-01-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  4. Antifungal agents for onychomycosis: new treatment strategies to improve safety.

    PubMed

    Zane, Lee T; Chanda, Sanjay; Coronado, Dina; Del Rosso, James

    2016-01-01

    Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient's current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient. PMID:27136621

  5. 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

  6. 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

  7. 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...

  8. Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives.

    PubMed

    Wang, Xuesong; Gao, Sumei; Yang, Jian; Gao, Yang; Wang, Ling; Tang, Xiaorong

    2016-03-01

    A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim. PMID:26140452

  9. Study on Mutagenic Breeding of Bacillus Subtilis and Properties of Its Antifungal Substances

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Yao, Jianming

    2004-08-01

    Bacillus subtitles JA isolated by our laboratory produced a large amount of antifungal substances, which had strong inhibitory activity against various plant pathogenic fungi, such as Rhizoctonia solani, Fusarium graminearum and so on. Ion beam implantation as a new mutagenic methods was applied in our studay. After B. subtitles JA was implanted by N+ ions, a strain designated as B. subtitles JA-026 was screened and obtained, which had a higher ability to produce those antifungal substances. A series of experiments indicated that the antifungal substances were thermostable and partially sensitive to proteinases K and tryproteinase. When the fermentating broth was fractionated with ammonium sulphate of a final saturation of 70%, the precipitate-enhanced inhibitory activity while the supernatant lost this activity. It appeared that the antifungal substances were likely to be protein.

  10. 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 (16μg/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

  11. Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

    PubMed

    Lamoth, Frédéric; Damonti, Lauro; Alexander, Barbara D

    2016-06-01

    No clinical breakpoints are available to delineate antifungal drug efficacy in non-Aspergillus invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ≤0.5 μg/ml was significantly associated with better 6-week outcomes. PMID:27008871

  12. Synthesis and antifungal activity of some s-mercaptotriazolobenzothiazolyl amino acid derivatives.

    PubMed

    Aboelmagd, A; Ali, Ibrahim A I; Salem, Ezzeldin M S; Abdel-Razik, M

    2013-02-01

    A series of s-triazolobenzothiazolylthioacetyl/propionyl amino acid derivatives were synthesized with the aim of evaluating their antifungal activity. Their chemical structures were confirmed by (1)H, (13)C NMR, IR, mass spectrometry and elemental analyses. The synthesized derivatives were screened for their antifungal activity against Aspergillus flavus and Candida albicans. Five compounds (3, 5, 7c, 8 and 17) were found to possess high activity comparable to fluconazole at 100 μg/mL against C. albicans. PMID:23376218

  13. 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

  14. In vitro antifungal activity of coumarin extracted from Loeselia mexicana Brand.

    PubMed

    Navarro-García, Victor M; Rojas, Gabriela; Avilés, Margarita; Fuentes, Macrina; Zepeda, Gerardo

    2011-09-01

    The bis-coumarin daphnoretin and its monomeric precursors scopoletin and umbelliferone were isolated for the first time from the aerial part of Loeselia mexicana Brand (a vegetal species used in Mexican traditional medicine) using chromatographic techniques. The structures of these compounds were determined by (1) H and (13) C NMR analyses. These coumarins were evaluated for in vitro antifungal activity. The three compounds tested showed significant antifungal activity. PMID:21605187

  15. Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent.

    PubMed

    Rybak, Jeffrey M; Marx, Kayleigh R; Nishimoto, Andrew T; Rogers, P David

    2015-11-01

    Coinciding with the continually increasing population of immunocompromised patients worldwide, the incidence of invasive fungal infections has grown over the past 4 decades. Unfortunately, infections caused by both yeasts such as Candida and molds such as Aspergillus or Mucorales remain associated with unacceptably high morbidity and mortality. In addition, the available antifungals with proven efficacy in the treatment of these infections remain severely limited. Although previously available second-generation triazole antifungals have significantly expanded the spectrum of the triazole antifungal class, these agents are laden with shortcomings in their safety profiles as well as formulation and pharmacokinetic challenges. Isavuconazole, administered as the prodrug isavuconazonium, is the latest second-generation triazole antifungal to receive U.S. Food and Drug Administration approval. Approved for the treatment of both invasive aspergillosis and invasive mucormycosis, and currently under investigation for the treatment of candidemia and invasive candidiasis, isavuconazole may have therapeutic advantages over its predecessors. With clinically relevant antifungal potency against a broad range of yeasts, dimorphic fungi, and molds, isavuconazole has a spectrum of activity reminiscent of the polyene amphotericin B. Moreover, clinical experience thus far has revealed isavuconazole to be associated with fewer toxicities than voriconazole, even when administered without therapeutic drug monitoring. These characteristics, in an agent available in both a highly bioavailable oral and a β-cyclodextrin-free intravenous formulation, will likely make isavuconazole a welcome addition to the triazole class of antifungals. PMID:26598096

  16. Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital

    PubMed Central

    Vazin, Afsaneh; Davarpanah, Mohammad Ali; Ghalesoltani, Setareh

    2015-01-01

    To evaluate pattern of using of three antifungal drugs: fluconazole, amphotericin B and voriconazole, at the hematology–oncology and bone marrow transplant wards of one large teaching hospital. In a prospective cross-sectional study, we evaluated the appropriateness of using antifungal drugs in patients, using Infectious Disease Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) guidelines. All the data were recorded daily by a pharmacist in a form designed by a clinical pharmacist and infectious diseases specialist, for antifungals usage, administration, and monitoring. During the study, 116 patients were enrolled. Indications of prescribing amphotericin B, fluconazole, and voriconazole were appropriate according to guidelines in 83.4%, 80.6%, and 76.9% respectively. The duration of treatments were appropriate according to guidelines in 75%, 64.5%, and 71.1% respectively. The dose of voriconazole was appropriate according to guidelines in 46.2% of patients. None of the patients received salt loading before administration of amphotericin B. The most considerable problems with the mentioned antifungals were about the indications and duration of treatment. In addition, prehydration for amphotericin B and dosage of voriconazole were not completely compatible with the mentioned guidelines. A suitable combination of controlling the use of antifungals and educational programs could be essential for improving the general process of using antifungal drugs at our hospital. PMID:26064070

  17. In vitro antifungal activities of longan (Dimocarpus longan Lour.) seed extract.

    PubMed

    Rangkadilok, Nuchanart; Tongchusak, Songsak; Boonhok, Rachasak; Chaiyaroj, Sansanee C; Junyaprasert, Varaporn B; Buajeeb, Waranun; Akanimanee, Jaratluck; Raksasuk, Thida; Suddhasthira, Theeralaksna; Satayavivad, Jutamaad

    2012-04-01

    Longan, Dimocarpus longan Lour., contains polyphenolic compounds which exhibit several pharmacological properties. This study aims to evaluate antifungal activities of longan fruit extract in comparison to its active compounds. The results showed that longan seed exhibited antifungal activity against the opportunistic yeasts (Candida species and Cryptococcus neoformans). In contrast, longan pulp and whole fruit did not demonstrate any inhibitory effects. Ellagic acid showed the most potent antifungal activity followed by corilagin and gallic acid, respectively. Ellagic acid inhibited Candida parapsilosis and C. neoformans more effectively than Candida krusei and also some Candida albicans clinical strains. Baidam cultivar possessed higher antifungal activity (MIC=500-4000 μg/ml) as it contained higher contents of ellagic acid and gallic acid than Edor (MIC=1000-8000 μg/ml). For antibacterial activity, only corilagin and gallic acid possessed weak to moderate inhibitory effects against Staphylococcus aureus and Streptococcus mutans, respectively. Longan seed was then applied in the oral care products. Longan effervescent granule (5% extract) significantly reduced adhesion of C. albicans to acrylic strips. Mouthwash containing 0.5% extract exhibited good antifungal activity compared to a commercial product. These findings indicated that longan seed extract and its polyphenolic compounds can be used as an antifungal agent in oral care products for the treatment of opportunistic yeast infection. PMID:22245574

  18. 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

  19. Antifungal activity of silver and zinc complexes of sulfadrug derivatives incorporating arylsulfonylureido moieties.

    PubMed

    Mastrolorenzo, A; Scozzafava, A; Supuran, C T

    2000-08-01

    Two well known antimicrobial sulfonamides, sulfadiazine and sulfamerazine were reacted with arylsulfonyl isocyanates, affording several new arylsulfonylureido derivatives. These compounds were subsequently used as ligands (in the form of conjugate bases, as sulfonamide anions) for the preparation of metal complexes containing silver and zinc. The newly synthesized complexes, unlike the free ligands, proved to act as effective antifungal agents against several Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.5-5 microg/ml. The mechanism of antifungal action of these complexes seems to be different from that of the azole antifungals acting as lanosterol-14-alpha-demethylase inhibitors. Levels of sterols assayed in the fungi cultures treated with these new antifungals were equal in the absence or in the presence of the tested compounds. This is in strong contrast with similar experiments in which ketoconazole has been used as antifungal, when drastically reduced ergosterol amounts could be detected. Thus, it is probable that the inhibition of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls, imparts antifungal activity to the new metal complexes reported here. PMID:10915959

  20. 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

  1. Cyanobacteria, Lyngbya aestuarii and Aphanothece bullosa as antifungal and antileishmanial drug resources

    PubMed Central

    Kumar, Maheep; Tripathi, Manoj Kumar; Srivastava, Akanksha; Gour, Jalaj Kumar; Singh, Rakesh Kumar; Tilak, Ragini; Asthana, Ravi Kumar

    2013-01-01

    Objective To investigate two cyanobacteria isolated from different origins i.e. Lyngbya aestuarii (L. aestuarii) from brackish water and Aphanothece bullosa (A. bullosa) from fresh water paddy fields for antifungal and antileishmanila activity taking Candida albicans and Leishmania donovain as targets. Methods Biomass of L. aestuarii and A. bullosa were harvested after 40 and 60 d respectively and lyophilized twice in methanol (100%) and redissolved in methanol (5%) for bioassay. Antifungal bioassay was done by agar well diffusion method while antileishmanial, by counting cell numbers and flageller motility observation of promastigotes and amastigotes from L. donovani. Fluconazole and 5% methanol were used as control. Results Both the cyanobacteria were found to be potent source of antifungal activity keeping fluconazole as positive control, however, methanolic crude extract (15 mg/mL) of A. bullosa was found more potent (larger inhibition zone) over that of methanolic crude extract of L. aestuarii. Similarly antileishmanial activity of crude extract (24.0 mg/mL) of A. bullosa was superior over that of methanolic crude extract of L. aestuarii (25.6 mg/mL). Conclusions Antifungal and antileishmanial drugs are still limited in the market. Screening of microbes possessing antifungal and antileishmanial activity drug is of prime importance. Cyanobacteria are little explored in this context because most of the drugs in human therapy are derived from microorganisms, mainly bacterial, fungal and actinomycetes. Thus in the present study two cyanobacterial strains from different origins showed potent source of antifungal and antileishmanial biomolecules. PMID:23730558

  2. 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

  3. 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

  4. Emerging antifungal azoles and effects on Magnaporthe grisea.

    PubMed

    Mares, D; Romagnoli, C; Andreotti, E; Forlani, G; Guccione, S; Vicentini, C B

    2006-06-01

    Derivatives of pyrazolo[1,5-a][1, 3, 5]triazine-2,4-dione,pyrazolo[1,5-c][1, 3, 5]thiadiazine-2-one, pyrazolo[3,4-d][1, 3]thiazine-4-one, and pyrazolo[3,4-d][1, 3]thiazine-4-thione were screened for antifungal activity against the causal agent of rice blast disease, Magnaporthe grisea. The compounds were tested at doses ranging from 10 to 200mugml(-1), using the commercial fungicide tricyclazole as reference compound. All triazine derivatives inhibited the growth and pigmentation of the mycelia less effectively than tricyclazole. The thiadiazine derivatives proved to be more effective than their triazine counterparts, but only 4-(butylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2h) and 4-(cyclohexylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2j) were more effective than tricyclazole. Pyrazolo[3,4-d][1,3]thiazine-4-one derivatives were active only at the highest doses, whereas members of the pyrazolo[3,4-d][1,3]thiazine-4-thione series inhibited fungal growth at the lowest concentrations used, at which tricyclazole had no effect. A dose-dependent mechanism might be responsible for this effect, with lipophilicity as the governing factor. Within a given set, the presence of a cyclohexyl or an n-butyl group generally increased antifungal activity, with respect to both growth inhibition and cell de-pigmentation of the mycelium, suggesting that a higher lipophilicity might improve transport inside the cells. SEM and TEM of M. grisea hyphae showed that treatment with the most active substance (2h) caused significant ultrastructural effects, particularly on the endomembrane system, suggesting a mechanism of action similar to that of most azole fungicides. Dissimilarities were also observed, with no alterations of the cell wall evident. In conclusion, several compounds showed greater inhibition than tricyclazole, and therefore provide useful new chemistry for control of M. grisea infections. PMID:16769209

  5. Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds.

    PubMed

    Scorzoni, Liliana; Sangalli-Leite, Fernanda; de Lacorte Singulani, Junya; de Paula E Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

    2016-04-01

    In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy. PMID:26853122

  6. 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

  7. 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. PMID:26733987

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

    PubMed Central

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

    2015-01-01

    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-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-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

  9. 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

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

    PubMed

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

    2015-04-01

    The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. PMID:25066382

  11. Purification and characterization of an antifungal peptide with potent antifungal activity but devoid of antiproliferative and HIV reverse transcriptase activities from Legumi secchi beans.

    PubMed

    Lam, Sze Kwan; Ng, Tzi Bun

    2013-04-01

    A monomeric 9.4-kDa peptide with antifungal activity was isolated from seeds of Phaseolus vulgaris cv Legumi secchi by using a protocol that involved affinity chromatography on Blue-Sepharose, ion exchange chromatography on Q-Sepharose, and gel filtration on Superdex 75. It was adsorbed on Blue-Sepharose and unadsorbed on Q-Sepharose. Its N-terminal sequence resembled those of other leguminous defensins. It impeded mycelial growth in the fungi Helminthosporium maydis, Rhizoctonia solani, Mycosphaerella arachidicola, and Fusarium oxysporum with an IC(50) value of 9.5, 3.5, 1, and 9.2 μM, respectively, but there was no effect on Valsa mali. SYTOX Green uptake by R. solani indicated that the antifungal peptide induced fungal membrane permeabilization. In contrast to the majority of previously reported defensins/defensin-like peptides, Legumi secchi antifungal peptide did not reduce the viability of MCF-7 breast cancer cells and HepG2 hepatoma cells or inhibit HIV-1 reverse transcriptase, indicating a dissociation between antifungal, antiproliferative and HIV-1 reverse transcriptase inhibitory activities. PMID:23412767

  12. Novel antifungal mechanism of resveratrol: apoptosis inducer in Candida albicans.

    PubMed

    Lee, Juneyoung; Lee, Dong Gun

    2015-03-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known natural polyphenolic compound that has garnered considerable interest because of its bioavailability and pharmacokinetics in humans. Although the antimicrobial activity of resveratrol has recently been focused, however, the antifungal activity and its mechanism are still largely unknown. Here, we report for the first time the potential of resveratrol as an apoptosis inducer in the human pathogenic fungus Candida albicans. The results showed that resveratrol exerted its effects from the early to the late stages of apoptosis and involved the activity of reactive oxygen species, particularly hydroxyl radicals ((∙)OH). DiOC6(3) and JC-1 staining indicated that loss of mitochondrial membrane potential (ΔΨ m) is a key event in resveratrol-induced apoptosis. Finally, we investigated metacaspase activation resulting from mitochondrial dysfunction. The result showed that resveratrol strongly activated metacaspase and promoted cytochrome c release. In summary, resveratrol induces fungal apoptosis through a caspase-dependent mitochondrial pathway and is a potential agent for treating human fungal diseases. PMID:25413604

  13. 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 β-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.

  14. A9145, a New Adenine-Containing Antifungal Antibiotic: Fermentation

    PubMed Central

    Boeck, L. D.; Clem, G. M.; Wilson, M. M.; Westhead, J. E.

    1973-01-01

    A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by Streptomyces griseolus. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some long-chain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co2+, PO43?, and CaCO3, were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved O2 level was also critical, the optimal concentration being 3 10?2 to 4.5 10?2 ?mole of O2/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels. PMID:4208279

  15. Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives.

    PubMed

    Wu, Jia-Shou; Zhang, Xue; Zhang, Ying-Lao; Xie, Jian-Wu

    2015-05-01

    A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and ?-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 ?g mL(-1)). PMID:25820179

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

    PubMed

    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 β-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. PMID:24271031

  17. 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

  18. Potential of agricultural fungicides for antifungal drug discovery.

    PubMed

    Jampilek, Josef

    2016-01-01

    While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead-likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structure-activity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development. PMID:26549424

  19. Determination of antifungal activities in serum samples from mice treated with different antifungal drugs allows detection of an active metabolite of itraconazole.

    PubMed

    Maki, Katsuyuki; Watabe, Etsuko; Iguchi, Yumi; Nakamura, Hideko; Tomishima, Masaki; Ohki, Hidenori; Yamada, Akira; Matsumoto, Satoru; Ikeda, Fumiaki; Tawara, Shuichi; Mutoh, Seitaro

    2006-01-01

    To establish an in vitro method of predicting in vivo efficacy of antifungal drugs against Candida albicans and Aspergillus fumigatus, the antifungal activities of fluconazole, itraconazole, and amphotericin B were determined in mouse serum. The minimum inhibitory concentration (MIC) of each drug was measured using mouse serum as a diluent. For C. albicans, the assay endpoint of azoles was defined as inhibition of mycelial extension (mMIC) and for A. fumigatus, as no growth (MIC). The MICs of amphotericin B for both pathogens were defined as the MIC at which no mycelial growth occurred. Serum MIC or mMIC determinations were then used to estimate the concentration of the drugs in serum of mice treated with antifungal drugs by multiplying the antifungal titer of the serum samples by the serum (m)MIC. The serum drug concentrations were also determined by HPLC. The serum concentrations estimated microbiologically showed good agreement with those determined by HPLC, except for itraconazole. Analysis of the serum samples from itraconazole-treated mice by a sensitive bioautography revealed the presence of additional spots, not seen in control samples of itraconazole. The bioautography assay demonstrated that the additional material detected in serum from mice treated with itraconazole was an active metabolite of itraconazole. The data showed that the apparent reduction in the itraconazole serum concentration as determined by HPLC was the result of the formation of an active metabolite, and that the use of a microbiological method to measure serum concentrations of drugs can provide a method for prediction of in vivo efficacy of antifungal drugs. PMID:16625050

  20. Production of a defensin-like antifungal protein NFAP from Neosartorya fischeri in Pichia pastoris and its antifungal activity against filamentous fungal isolates from human infections.

    PubMed

    Virágh, Máté; Vörös, Dóra; Kele, Zoltán; Kovács, Laura; Fizil, Ádám; Lakatos, Gergely; Maróti, Gergely; Batta, Gyula; Vágvölgyi, Csaba; Galgóczy, László

    2014-02-01

    Neosartorya fischeri NRRL 181 isolate secretes a defensin-like antifungal protein (NFAP) which has a remarkable antifungal effect against ascomycetous filamentous fungi. This protein is a promising antifungal agent of biotechnological value; however in spite of the available knowledge of the nature of its 5'-upstream transcriptional regulation elements, the bulk production of NFAP has not been resolved yet. In this study we carried out its heterologous expression in the yeast Pichia pastoris and investigated the growth inhibition effect exerted by the heterologous NFAP (hNFAP) on filamentous fungal isolates from human infections compared with what was caused by the native NFAP. P. pastoris KM71H transformant strain harboring the pPICZαA plasmid with the mature NFAP encoding gene produced the protein. The final yield of the hNFAP was sixfold compared to the NFAP produced by N. fischeri NRRL 181. Based on the signal dispersion of the amide region, it was proven that the hNFAP exists in folded state. The purified hNFAP effectively inhibited the growth of fungal isolates belonging to the Aspergillus and to the Fusarium genus, but all investigated zygomycetous strain proved to be insusceptible. There was no significant difference between the growth inhibition effect exerted by the native and the heterologous NFAP. These data indicated that P. pastoris KM71H can produce the NFAP in an antifungally active folded state. Our results provide a base for further research, e.g., investigation the connection between the protein structure and the antifungal activity using site directed mutagenesis. PMID:24269762

  1. Antifungal activity of borrelidin produced by a Streptomyces strain isolated from soybean.

    PubMed

    Liu, Chong-Xi; Zhang, Ji; Wang, Xiang-Jing; Qian, Ping-Ting; Wang, Ji-Dong; Gao, Ya-Mei; Yan, Yi-Jun; Zhang, Shu-Zhen; Xu, Peng-Fei; Li, Wen-Bin; Xiang, Wen-Sheng

    2012-02-01

    In this study, an endophytic Streptomyces sp. neau-D50 with strong antifungal activity against Phytophthora sojae was isolated from healthy soybean root, using an in vitro screening technique. A bioactivity-guided approach was then employed to isolate and determine the chemical identity of bioactive constituents with antifungal activity from strain neau-D50. The structure of the antifungal metabolite was elucidated as borrelidin on the basis of spectral analysis. To our knowledge, this is the first report that borrelidin has strong antifungal activity against dominant race 1 of P. sojae with EC(50) and EC(95) of 0.0056 and 0.026 mg/L, respectively. The values were respectively 62.5- and 262.3-fold lower than those of the commercial fungicide metalaxyl, which has been used to treat soybean seed for the control of P. sojae . The in situ bioassays demonstrated that borrelidin at 10 mg/L reduced P. sojae race 1 lesions on soybean seedlings by 94.72% without affecting root growth. Thus, borrelidin might be a promising candidate for new antifungal agents against P. sojae. PMID:22242825

  2. Antifungal property of hibicuslide C and its membrane-active mechanism in Candida albicans.

    PubMed

    Hwang, Ji Hong; Jin, Qinglong; Woo, Eun-Rhan; Lee, Dong Gun

    2013-10-01

    In this study, the antifungal activity and mode of action(s) of hibicuslide C derived from Abutilon theophrasti were investigated. Antifungal susceptibility testing showed that hibicuslide C possessed potent activities toward various fungal strains and less hemolytic activity than amphotericin B. To understand the antifungal mechanism(s) of hibicuslide C in Candida albicans, flow cytometric analysis with propidium iodide was done. The results showed that hibicuslide C perturbed the plasma membrane of the C. albicans. The analysis of the transmembrane electrical potential with 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] indicated that hibicuslide C induced membrane depolarization. Furthermore, model membrane studies were performed with calcein encapsulating large unilamellar vesicles (LUVs) and FITC-dextran (FD) loaded LUVs. These results demonstrated that the antifungal effects of hibicuslide C on the fungal plasma membrane were through the formation of pores with radii between 2.3 nm and 3.3 nm. Finally, in three dimensional flow cytometric contour plots, a reduced cell sizes by the pore-forming action of hibicuslide C were observed. Therefore, the present study suggests that hibicuslide C exerts its antifungal effect by membrane-active mechanism. PMID:23816874

  3. Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    PubMed Central

    de Arajo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendona, Francisco J. B.; Barbosa-Filho, Jos M.

    2013-01-01

    The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 ?g/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

  4. Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus.

    PubMed

    Lamoth, Frédéric; Juvvadi, Praveen R; Steinbach, William J

    2016-03-01

    Invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. The efficacy of current anti-Aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). The heat shock protein 90 (Hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast Candida albicans. Few studies have addressed its role in filamentous fungi such as Aspergillus fumigatus, in which mechanisms of resistance may differ substantially. Hsp90 is at the center of a complex network involving calcineurin, lysine deacetylases (KDAC) and other client proteins, which orchestrate compensatory repair mechanisms of the cell wall in response to the stress induced by antifungals. In A. fumigatus, Hsp90 is a trigger for resistance to high concentrations of caspofungin, known as the paradoxical effect. Disrupting Hsp90 circuitry by different means (Hsp90 inhibitors, KDAC inhibitors and anti-calcineurin drugs) potentiates the antifungal activity of caspofungin, thus representing a promising novel antifungal approach. This review will discuss the specific features of A. fumigatus Hsp90 and the potential for antifungal strategies of invasive aspergillosis targeting this essential chaperone. PMID:25243616

  5. Factors affecting antifungal activity of Streptomyces philanthi RM-1-138 against Rhizoctonia solani.

    PubMed

    Boukaew, Sawai; Prasertsan, Poonsuk

    2014-01-01

    Sheath blight disease of rice caused by Rhizoctonia solani Kühn is economically important disease in most of the world's rice growing areas. The disease causes severe yield losses of >20% of rice in Thailand. Our previous investigation reported the antifungal activity of Streptomyces philanthi RM-1-138 against R. solani PTRRC-9. In this study, glucose yeast-malt extract medium, initial pH of 7.5 and a temperature of 30 °C were found to be optimum for both cell growth and antifungal activity of S. philanthi RM-1-138. The inhibition of 94 and 100% on the growth of R. solani PTRRC-9 were achieved from the antifungal metabolites of the 6 and 9-days-old culture filtrates of S. philanthi RM-1-138, respectively. Heat treatment on the culture filtrate had slight effect on its antifungal activity. The culture broth demonstrated higher antifungal activity on growth of R. solani PTRRC-9 (90.4%) than the culture filtrate (31.5%) and its effective dose was at 0.1% (v/v). The present results indicated the possibilities of using either the culture broth or culture filtrate of S. philanthi RM-1-138 to inhibit growth of R. solani PTRRC-9. PMID:23839715

  6. Fumigant antifungal activity of Myrtaceae essential oils and constituents from Leptospermum petersonii against three Aspergillus species.

    PubMed

    Kim, Eunae; Park, Il-Kwon

    2012-01-01

    Commercial plant essential oils obtained from 11 Myrtaceae plant species were tested for their fumigant antifungal activity against Aspergillus ochraceus, A. flavus, and A. niger. Essential oils extracted from Leptospermum petersonii at air concentrations of 56 × 10(-3) mg/mL and 28 × 10(-3) mg/mL completely inhibited the growth of the three Aspergillus species. However, at an air concentration of 14 × 10(-3) mg/mL, inhibition rates of L. petersonii essential oils were reduced to 20.2% and 18.8% in the case of A. flavus and A. niger, respectively. The other Myrtaceae essential oils (56 × 10(-3) mg/mL) only weakly inhibited the fungi or had no detectable affect. Gas chromatography-mass spectrometry analysis identified 16 compounds in L. petersonii essential oil. The antifungal activity of the identified compounds was tested individually by using standard or synthesized compounds. Of these, neral and geranial inhibited growth by 100%, at an air concentration of 56 × 10(-3) mg/mL, whereas the activity of citronellol was somewhat lover (80%). The other compounds exhibited only moderate or weak antifungal activity. The antifungal activities of blends of constituents identified in L. petersonii oil indicated that neral and geranial were the major contributors to the fumigant and antifungal activities. PMID:22945026

  7. 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

  8. Biosynthesis of an antifungal oligopeptide in Burkholderia contaminans strain MS14.

    PubMed

    Gu, Ganyu; Smith, Leif; Wang, Nian; Wang, Hui; Lu, Shi-En

    2009-03-01

    Strain MS14, exhibiting antifungal activity, was classified to belong to Burkholderia contaminans. When compared with the wild type strain, antifungal activities of mutants MS14MT13 and MS14MT18 against Geotrichum candidum were eliminated, and the activity of mutant MS14MT15 was reduced by approximately 80%. Sequence analysis of a 22.7-kb DNA segment revealed the presence of six open-reading frames (ORFs), including the genes disrupted in the mutants. The wild type level of antifungal activity was observed for mutant MS14MT15 (ambR2::Tn5) complemented in trans with the intact ambR2 gene, which encodes a LuxR type regulator. AmbR2 positively regulates the transcription of the other five ORFs identified, which including two nonribosomal peptide synthetase genes required for biosynthesis of antifungal compound. The compound consists of amino acid residues having a molecular weight of 1200.6 Da. These results show that strain MS14 possesses a novel set of genes dedicated to the biosynthesis of an antifungal oligopeptide. PMID:19167363

  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. 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

  11. 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

  12. 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 α-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 α-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

  13. Glucose Directly Promotes Antifungal Resistance in the Fungal Pathogen, Candida spp.

    PubMed Central

    Mandal, Santi M.; Mahata, Denial; Migliolo, Ludovico; Parekh, Aditya; Addy, Partha S.; Mandal, Mahitosh; Basak, Amit

    2014-01-01

    Effects of glucose on the susceptibility of antifungal agents were investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents; voriconazole was the most affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interactions between antifungal agents with glucose molecules were investigated using isothermal titration calorimetry, Fourier transform infrared, and 1H NMR. Glucose has a higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility of antifungal agents during chemotherapy. In addition to confirming the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the glucose. In vivo results also suggest that the physiologically relevant higher glucose level in the bloodstream of diabetes mellitus mice might interact with the available selective agents during antifungal therapy, thus decreasing glucose activity by complex formation. Thus, proper selection of drugs for diabetes mellitus patients is important to control infectious diseases. PMID:25053418

  14. 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 α-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 α-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

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

    PubMed Central

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

    2015-01-01

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

  16. Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts

    PubMed Central

    Goughenour, Kristie D.; Balada-Llasat, Joan-Miquel

    2015-01-01

    Standardized methodologies for determining the antifungal susceptibility of fungal pathogens is central to the clinical management of invasive fungal disease. Yeast-form fungi can be tested using broth macrodilution and microdilution assays. Reference procedures exist for Candida species and Cryptococcus yeasts; however, no standardized methods have been developed for testing the antifungal susceptibility of yeast forms of the dimorphic systemic fungal pathogens. For the dimorphic fungal pathogen Histoplasma capsulatum, susceptibility to echinocandins differs for the yeast and the filamentous forms, which highlights the need to employ Histoplasma yeasts, not hyphae, in antifungal susceptibility tests. To address this, we developed and optimized methodology for the 96-well microtiter plate-based measurement of Histoplasma yeast growth in vitro. Using optical density, the assay is quantitative for fungal growth with a dynamic range greater than 30-fold. Concentration and assay reaction time parameters were also optimized for colorimetric (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction) and fluorescent (resazurin reduction) indicators of fungal vitality. We employed this microtiter-based assay to determine the antifungal susceptibility patterns of multiple clinical isolates of Histoplasma representing different phylogenetic groups. This methodology fulfills a critical need for the ability to monitor the effectiveness of antifungals on Histoplasma yeasts, the morphological form present in mammalian hosts and, thus, the form most relevant to disease. PMID:26246483

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

    PubMed

    Maswada, Hanafey F; Abdallah, Sabry A

    2013-12-01

    Plant extracts appear to be one of the most effective alternative methods of plant diseases control which are less harmful to human beings and environment. In vitro antifungal activity of methanolic extracts of three promising wild geophytic plants against three post-harvest pathogenic fungi using radial growth technique was conducted. These extracts included the shoot system (S) and underground parts (R) of Asparagus stipularis, Cyperus capitatus and Stipagrostis lanata. The tested fungi were Alternaria solani, Aspergillus niger and Rhizopus stolonifer. The results exhibited that, all plant extracts had antifungal activity against the tested fungi. The antifungal activity greatly varied depending on plant parts and/or plant species. R. stolonifer was the most susceptible fungus to the tested plant extracts followed by A. niger and then A. solani. On the other hand, the most effective plant extracts against tested fungi were S. lanata (S) and A. stipularis (R). The most effective plant extracts against R. stolonifer were S. lanata (R) and C. capitatus (S). While, the extracts of A. stipularis (R) and S. lanata (S) were the most effective against A. niger. The extracts of C. capitatus (S) and S. lanata (S) exhibited the highest antifungal activity against A. solani. The results demonstrated that, the methanolic extracts of A. stipularis, C. capitatus and S. lanata had potential antifungal activity against A. solani, A. niger and R. stolonifer. PMID:24506036

  18. Koningiopisins A-H, Polyketides with Synergistic Antifungal Activities from the Endophytic Fungus Trichoderma koningiopsis.

    PubMed

    Liu, Kai; Yang, Yabin; Miao, Cui-Ping; Zheng, You-Kun; Chen, Jin-Lian; Chen, You-Wei; Xu, Li-Hua; Guang, Hui-Lin; Ding, Zhong-Tao; Zhao, Li-Xing

    2016-03-01

    Eight new fungal polyketides named koningiopisins A-H (1-8) and four previously known polyketides (9-12) were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH 30 002. Their structures were elucidated using extensive spectral data interpretation, and their antifungal and synergistic activities were also evaluated. Koningiopisin C (3) exhibited in vitro antifungal activity against the phytopathogenic fungus Plectosphaerella cucumerina with an MIC of 16 µg/mL. Although the antifungal activities of single compounds were not obvious, a mixture of six compounds (4-9) exhibited potent synergistic antifungal activity against P. cucumerina with an MIC of 16 µg/mL, and the antifungal activity of the mixture of any two compounds with a 1 : 1 ratio was better than that observed from the individual compound. The synergistic biological activity of the metabolites in YIM PH 30 002 demonstrates the significant ecological function of the endophyte for its host plant, and provides additional insight into the search for and development of agents for biological control. PMID:26692458

  19. Antifungal Potential of Extracellular Metabolites Produced by Streptomyces hygroscopicus against Phytopathogenic Fungi

    PubMed Central

    Prapagdee, Benjaphorn; Kuekulvong, Chutima; Mongkolsuk, Skorn

    2008-01-01

    Indigenous actinomycetes isolated from rhizosphere soils were assessed for in vitro antagonism against Colletotrichum gloeosporioides and Sclerotium rolfsii. A potent antagonist against both plant pathogenic fungi, designated SRA14, was selected and identified as Streptomyces hygroscopicus. The strain SRA14 highly produced extracellular chitinase and ?-1,3-glucanase during the exponential and late exponential phases, respectively. Culture filtrates collected from the exponential and stationary phases inhibited the growth of both the fungi tested, indicating that growth suppression was due to extracellular antifungal metabolites present in culture filtrates. The percentage of growth inhibition by the stationary culture filtrate was significantly higher than that of exponential culture filtrate. Morphological changes such as hyphal swelling and abnormal shapes were observed in fungi grown on potato dextrose agar that contained the culture filtrates. However, the antifungal activity of exponential culture filtrates against both the experimental fungi was significantly reduced after boiling or treatment with proteinase K. There was no significant decrease in the percentage of fungal growth inhibition by the stationary culture filtrate that was treated as above. These data indicated that the antifungal potential of the exponential culture filtrate was mainly due to the presence of extracellular chitinase enzyme, whereas the antifungal activity of the stationary culture filtrate involved the action of unknown thermostable antifungal compound(s). PMID:18825279

  20. 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

  1. Chemical composition of essential oils of Thymus and Mentha species and their antifungal activities.

    PubMed

    Sokovi?, Marina D; Vukojevi?, Jelena; Marin, Petar D; Brki?, Dejan D; Vajs, Vlatka; van Griensven, Leo J L D

    2009-01-01

    The potential antifungal effects of Thymus vulgaris L., Thymus tosevii L., Mentha spicata L., and Mentha piperita L. (Labiatae) essential oils and their components against 17 micromycetal food poisoning, plant, animal and human pathogens are presented. The essential oils were obtained by hydrodestillation of dried plant material. Their composition was determined by GC-MS. Identification of individual constituents was made by comparison with analytical standards, and by computer matching mass spectral data with those of the Wiley/NBS Library of Mass Spectra. MIC's and MFC's of the oils and their components were determined by dilution assays. Thymol (48.9%) and p-cymene (19.0%) were the main components of T. vulgaris, while carvacrol (12.8%), a-terpinyl acetate (12.3%), cis-myrtanol (11.2%) and thymol (10.4%) were dominant in T. tosevii. Both Thymus species showed very strong antifungal activities. In M. piperita oil menthol (37.4%), menthyl acetate (17.4%) and menthone (12.7%) were the main components, whereas those of M. spicata oil were carvone (69.5%) and menthone (21.9%). Mentha sp. showed strong antifungal activities, however lower than Thymus sp. The commercial fungicide, bifonazole, used as a control, had much lower antifungal activity than the oils and components investigated. It is concluded that essential oils of Thymus and Mentha species possess great antifungal potential and could be used as natural preservatives and fungicides. PMID:19136911

  2. Unusual Susceptibility of a Multidrug-Resistant Yeast Strain to Peptidic Antifungals

    PubMed Central

    Milewski, Sławomir; Mignini, Fiorenzo; Prasad, Rajendra; Borowski, Edward

    2001-01-01

    The susceptibility of Saccharomyces cerevisiae JG436 multidrug transporter deletion mutant, Δpdr5, to several antifungal agents was compared to that of JG436-derived JGCDR1 and JGCaMDR1 transformants, harboring the CDR1 and CaMDR1 genes, encoding the main drug-extruding membrane proteins of Candida albicans. The JGCDR1 and JGCaMDR1 yeasts demonstrated markedly diminished susceptibility to the azole antifungals, terbinafine and cycloheximide, while that to amphotericin B was unchanged. Surprisingly, JGCDR1 but not JGCaMDR1 cells showed enhanced susceptibility to peptidic antifungals, rationally designed compounds containing inhibitors of glucosamine-6-phosphate synthase. It was found that these antifungal oligopeptides, as well as model oligopeptides built of proteinogenic amino acids, were not effluxed from JGCDR1 cells. Moreover, they were taken up by these cells at rates two to three times higher than by JG436. The tested oligopeptides were rapidly cleaved to constitutive amino acids by cytoplasmic peptidases. Studies on the mechanism of the observed phenomenon suggested that an additive proton motive force generated by Cdr1p stimulated uptake of oligopeptides into JGCDR1 cells, thus giving rise to the higher antifungal activity of FMDP [N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid]-peptides. PMID:11120970

  3. An antifungal compound involved in symbiotic germination of Cypripedium macranthos var. rebunense (Orchidaceae).

    PubMed

    Shimura, Hanako; Matsuura, Mayumi; Takada, Noboru; Koda, Yasunori

    2007-05-01

    Germination of orchid seeds fully depends on a symbiotic association with soil-borne fungi, usually Rhizoctonia spp. In contrast to the peaceful symbiotic associations between many other terrestrial plants and mycorrhizal fungi, this association is a life-and-death struggle. The fungi always try to invade the cytoplasm of orchid cells to obtain nutritional compounds. On the other hand, the orchid cells restrict the growth of the infecting hyphae and obtain nutrition by digesting them. It is likely that antifungal compounds are involved in the restriction of fungal growth. Two antifungal compounds, lusianthrin and chrysin, were isolated from the seedlings of Cypripedium macranthos var. rebunense that had developed shoots. The former had a slightly stronger antifungal activity than the latter, and the antifungal spectra of these compounds were relatively specific to the nonpathogenic Rhizoctonia spp. The level of lusianthrin, which was very low in aseptic protocorm-like bodies, dramatically increased following infection with the symbiotic fungus. In contrast, chrysin was not detected in infected protocorm-like bodies. These results suggest that orchid plants equip multiple antifungal compounds and use them at specific developmental stages; lusianthrin maintains the perilous symbiotic association for germination and chrysin helps to protect adult plants. PMID:17445846

  4. Components of the calcium-calcineurin signaling pathway in fungal cells and their potential as antifungal targets.

    PubMed

    Liu, Shuyuan; Hou, Yinglong; Liu, Weiguo; Lu, Chunyan; Wang, Weixin; Sun, Shujuan

    2015-04-01

    In recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calcium-calcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca(2+) homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs. PMID:25636321

  5. Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

    PubMed Central

    Liu, Shuyuan; Hou, Yinglong; Liu, Weiguo; Lu, Chunyan; Wang, Weixin

    2015-01-01

    In recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calcium-calcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca2+ homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs. PMID:25636321

  6. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

  7. 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.

  8. Laccase Catalyzed Synthesis of Iodinated Phenolic Compounds with Antifungal Activity

    PubMed Central

    Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

    2014-01-01

    Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

  9. 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

    2016-04-01

    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.

  10. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

    PubMed Central

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong

    2015-01-01

    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

  11. Antifungal drug resistance evokedvia RNAi-dependent epimutations

    PubMed Central

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

    2014-01-01

    Microorganisms evolve via mechanisms spanning sexual/parasexual reproduction, mutators, aneuploidy, Hsp90, and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show 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 peptidyl-prolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin1. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth2. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance (FK506R) and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the FKBP12 fkbA gene, giving rise to drug-resistant epimutants. FK506R epimutants readily reverted to the drug-sensitive wild-type (WT) phenotype when grown without drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNA (sRNA) and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves generation of a double-stranded RNA (dsRNA) trigger intermediate from the fkbA mature mRNA 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

  12. 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.

  13. 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

  14. Synthesis and characterization of dithiocarbamate chitosan derivatives with enhanced antifungal activity.

    PubMed

    Qin, Yukun; Liu, Song; Xing, Ronge; Yu, Huahua; Li, Kecheng; Meng, Xiangtao; Li, Rongfeng; Li, Pengcheng

    2012-06-20

    In this study, ammonium dithiocarbamate chitosan (ADTCCS) and triethylene diamine dithiocarbamate chitosan (TEDADTCCS) derivatives were obtained respectively by mixing chitosan with carbon disulfide and ammonia (triethylenediamine). Their structures were confirmed by FT-IR, 1H NMR, XRD, DSC, SEM, and elemental analysis. Antifungal properties of them against the plant pathogenic fungi Fusarium oxysporum and Alternaria porri were investigated at concentrations ranged from 31.25 to 500 mg/L. The dithiocarbamate chitosan derivatives had enhanced antifungal activity compared with chitosan. Particularly, they showed obvious inhibitory effect on Fusarium oxysporum. At 500 mg/L, TEDADTCCS inhibited growth of F. oxysporum at 60.4%, stronger than polyoxin and triadimefon whose antifungal indexes were found to be 25.3% and 37.7%. The chitosan derivatives described here deserve further study for use in crop protection. PMID:24750734

  15. Using Galleria mellonella-Candida albicans infection model to evaluate antifungal agents.

    PubMed

    Li, De-Dong; Deng, Li; Hu, Gan-Hai; Zhao, Lan-Xue; Hu, Dan-Dan; Jiang, Yuan-Ying; Wang, Yan

    2013-01-01

    Candida albicans is the most common fungal pathogen. Galleria mellonella is widely used as an infection model host. Nevertheless, the G. mellonella-C. albicans infection model had not been optimized for drug evaluation before this study. In this work, we revealed that 5 × 10(5) colony forming unit (CFU)/larva was a suitable inoculum to optimize the G. mellonella-C. albicans infection model in order to evaluate antifungal agents. Using our optimized model, the antifungal effect of fluconazole, amphotericin B and flucytosine, and the synergy between amphotericin B and flucytosine were successfully verified. Thus, this study provides a rapid, inexpensive and reliable way to evaluate antifungals in vivo. PMID:23995660

  16. The Role of Antifungals against Candida Biofilm in Catheter-Related Candidemia

    PubMed Central

    Bouza, Emilio; Guinea, Jesús; Guembe, María

    2014-01-01

    Catheter-related bloodstream infection (C-RBSI) is one of the most frequent nosocomial infections. It is associated with high rates of morbidity and mortality. Candida spp. is the third most common cause of C-RBSI after coagulase-negative staphylococci and Staphylococcus aureus and is responsible for approximately 8% of episodes. The main cause of catheter-related candidemia is the ability of some Candida strains—mainly C. albicans and C. parapsilosis—to produce biofilms. Many in vitro and in vivo models have been designed to assess the activity of antifungal drugs against Candida biofilms. Echinocandins have proven to be the most active antifungal drugs. Potential options in situations where the catheter cannot be removed include the combination of systemic and lock antifungal therapy. However, well-designed and -executed clinical trials must be performed before firm recommendations can be issued.

  17. Antifungal activity of essential oil from fruits of Indian Cuminum cyminum.

    PubMed

    Romagnoli, Carlo; Andreotti, Elisa; Maietti, Silvia; Mahendra, Rai; Mares, Donatella

    2010-07-01

    The essential oil of fruits of Cuminum cyminum L. (Apiaceae), from India, was analyzed by GC and GC-MS, and its antifungal activity was tested on dermatophytes and phytopathogens, fungi, yeasts and some new Aspergilli. The most abundant components were cumin aldehyde, pinenes, and p-cymene, and a fraction of oxygenate compounds such as alcohol and epoxides. Because of the large amount of the highly volatile components in the cumin extract, we used a modified recent technique to evaluate the antifungal activity only of the volatile parts at doses from 5 to 20 microL of pure essential oil. Antifungal testing showed that Cuminum cyminum is active in general on all fungi but in particular on the dermatophytes, where Trichophyton rubrum was the most inhibited fungus also at the lowest dose of 5 microL. Less sensitive to treatment were the phytopathogens. PMID:20645785

  18. Characterization of Diterpenes from Euphorbia prolifera and Their Antifungal Activities against Phytopathogenic Fungi.

    PubMed

    Xu, Jing; Kang, Jing; Cao, Xiangrong; Sun, Xiaocong; Yu, Shujing; Zhang, Xiao; Sun, Hongwei; Guo, Yuanqiang

    2015-07-01

    Euphorbia prolifera is a poisonous plant belonging to the Euphorbiaceae family. In this survey on plant secondary metabolites to obtain bioactive substances for the development of new antifungal agents for agriculture, the chemical constituents of the plant E. prolifera were investigated. This procedure led to the isolation of six new and two known diterpenes. Their structures, including absolute configurations, were elucidated on the basis of extensive NMR spectroscopic data analyses and time-dependent density functional theory ECD calculations. Biological screenings revealed that these diterpenes possessed antifungal activities against three phytopathogenic fungi. The results of the phytochemical investigation further revealed the chemical components of the poisonous plant E. prolifera, and biological screenings implied the extract or bioactive diterpenes from this plant may be regarded as candidate agents of antifungal agrochemicals for crop protection products. PMID:26063581

  19. 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.

  20. Antifungal activity of chemically different essential oils from wild Tunisian Thymus spp.

    PubMed

    Maissa, Ben Jabeur; Walid, Hamada

    2015-01-01

    Essential oils isolated by using hydrodistillation from the aerial parts of Thymus algeriensis and Thymus capitatus Hoff. et Link. from different locations of Tunisia (Kef, Takelsa, Zaghouan, Fahs and Toukeber) were characterised. The chemical composition was analysed by using gas chromatography/mass spectrometry, the major component of T. capitatus from Kef and T. algeriensis was thymol while carvacrol was the main component of T. capitatus from Zaghouan, Fahs and Toukeber. The antifungal activity of the oils and some pure components was assessed by the in vitro assay against several fungi and oomycetes. T. capitatus (chemotype carvacrol) exhibited the strongest antifungal activity followed by T. capitatus (chemotype thymol) and T. algeriensis, indicating that carvacrol might have a stronger antifungal activity than thymol. PMID:25484099

  1. Synthesis, In Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents.

    PubMed

    Li, Xiang; Liu, Chao; Tang, Sheng; Wu, Qiuye; Hu, Honggang; Zhao, Qingjie; Zou, Yan

    2016-01-01

    Based on the structure of the active site of CYP51 and the structure-activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1-{1-[2-(substitutedbenzyloxy)ethyl]-1H-1,2,3-triazol-4-yl}-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols (6a-n) were designed and synthesized utilizing copper-catalyzed azide-alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π-π interactions, hydrophobic interactions, and the narrow hydrophobic cleft. PMID:26641629

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

    PubMed

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

    2015-03-01

    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

  3. 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

  4. Chemical characterization and antifungal activity of essential oil of capitula from wild Indian Tagetes patula L.

    PubMed

    Romagnoli, C; Bruni, R; Andreotti, E; Rai, M K; Vicentini, C B; Mares, D

    2005-04-01

    The essential oil extracted by steam distillation from the capitula of Indian Tagetes patula, Asteraceae, was evaluated for its antifungal properties and analyzed by gas chromatography and gas chromatography-mass spectrometry. Thirty compounds were identified, representing 89.1% of the total detected. The main components were piperitone (24.74%), piperitenone (22.93%), terpinolene (7.8%), dihydro tagetone (4.91%), cis-tagetone (4.62%), limonene (4.52%), and allo-ocimene (3.66%). The oil exerted a good antifungal activity against two phytopathogenic fungi, Botrytis cinerea and Penicillium digitatum, providing complete growth inhibition at 10 microl/ml and 1.25 microl/ml, respectively. The contribution of the two main compounds, piperitone and piperitenone, to the antifungal efficacy was also evaluated and ultrastructural modifications in mycelia were observed via electron microscopy, evidencing large alterations in hyphal morphology and a multisite mechanism of action. PMID:15868213

  5. Halogenated benzoate derivatives of altholactone with improved anti-fungal activity.

    PubMed

    Euanorasetr, Jirayut; Junhom, Mayura; Tantimavanich, Srisurang; Vorasin, Onanong; Munyoo, Bamroong; Tuchinda, Patoomratana; Panbangred, Watanalai

    2016-05-01

    Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml(-1) against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1-15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml(-1), while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11-13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml(-1). In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group. PMID:26765144

  6. 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

  7. Evaluation of topical antifungal products in an in vitro onychomycosis model.

    PubMed

    Sleven, Reindert; Lanckacker, Ellen; Delputte, Peter; Maes, Louis; Cos, Paul

    2016-05-01

    Many topical commercial products are currently available for the treatment of onychomycosis. However, limited data are available concerning their antifungal activity. Using an in vitro onychomycosis model, the daily application of seven nail formulations was compared to the antifungal reference drug amorolfine (Loceryl(®) ) and evaluated for inhibitory activity against Trichophyton mentagrophytes using an agar diffusion test. Of all commercial nail formulations, only Excilor(®) and Nailner(®) demonstrated inhibitory activity, which was much lower compared to the daily application of Loceryl(®) . However, Excilor(®) showed similar efficacy compared to the conventional weekly application of Loceryl(®) . These results suggest a role for organic acids in the antifungal effect of Excilor(®) (acetic acid, ethyl lactate) and Nailner(®) (lactic acid, citric acid, ethyl lactate) as all tested formulations without organic acids were inactive. PMID:26857689

  8. Transcriptional regulation of drug-resistance genes in Candida albicans biofilms in response to antifungals.

    PubMed

    Watamoto, T; Samaranayake, L P; Egusa, H; Yatani, H; Seneviratne, C J

    2011-09-01

    Biofilm formation is a major virulence attribute of Candida albicans and is directly associated with therapeutic failure. One method by which Candida acquires antifungal resistance is the expression of drug-resistance genes. This study aimed to evaluate the transcriptional regulation of several genes associated with antifungal resistance of C. albicans under planktonic, recently adhered and biofilm growth modes and in C. albicans biofilms in response to antifungal agents. Initially, the antifungal susceptibility of C. albicans cultures in different growth modes was evaluated by standard antifungal susceptibility testing. Next, to assess CDR1, CDR2, MDR1, ERG11, FKS1 and PIL1 expression, RNA was harvested from cells in each growth mode, and from biofilms after drug treatment, and subjected to quantitative real-time RT-PCR (qRT-PCR). Biofilm C. albicans was more resistant to antifungals than recently adhered cells and stationary-phase planktonic cultures. Transcriptional expression of CDR1, CDR2, MDR1, ERG11 and FKS1 was lower in recently adhered C. albicans than in the stationary-phase planktonic cultures. In contrast, PIL1 levels were significantly increased in recently adhered and biofilm modes of growth. The expression of MDR1 in biofilms greatly increased on challenge with amphotericin B but not with the other drugs tested (P<0.01). ERG11 was significantly upregulated by ketoconazole (P<0.01). Caspofungin and amphotericin B significantly upregulated FKS1 expression, whereas they significantly downregulated PIL1 expression (P<0.01). These results indicate that the expression of drug-resistance genes is associated with higher drug resistance of Candida biofilms, and lay a foundation for future large-scale genome-wide expression analysis. PMID:21474609

  9. Structure-Antifungal Activity Relationships of Polyene Antibiotics of the Amphotericin B Group

    PubMed Central

    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.

    2013-01-01

    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

  10. In Vitro and In Vivo antifungal activities of selected Cameroonian dietary spices

    PubMed Central

    2014-01-01

    Background Spices and herbs have been used in food since ancient times to give taste and flavor and also as food preservatives and disease remedies. In Cameroon, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their antifungal potential. The present work was designed to assess the antifungal properties of extracts from spices used in Cameroonian dietary. Methods The in vitro antifungal activities of twenty three extracts from twenty one spices were assessed by the broth micro-dilution method against eight fungi. Also, the in vivo activity of Olax subscorpioidea extract (the most active extract) was evaluated in rat model of disseminated candidiasis due to Candida albicans by estimating the fungal burden in blood and kidney. Results Seven extracts (30%) exhibited moderate to significant antifungal activities, inhibiting the growth of the microorganisms at concentrations ranging from 0.048 to 0.39 mg/mL. Olax subscorpioidea extract exhibited the highest antifungal activity particularly against Candida albicans and Candida tropicalis (MIC of 0.097 mg/mL and 0.048 mg/mL respectively). Sixteen extracts (70%) were weakly active (MICs > 6.25 mg/mL). Oral administration of O. subscorpioidea extract at the dose 2 g/kg of body weight (bw) to artificially infected rats revealed a drop in the number of colony forming units per milliliter (cfu/mL) of Candida albicans cells in the blood below the detection limit (100 cfu/mL) while a modest decrease was observed in the kidney. Conclusion The present work shows that some of the spices studied possess interesting antifungal properties and could be used to treat candidiasis. Among the plant species tested, Olax subscorpioidea displayed the most promising result. PMID:24533718

  11. Inhibition of adherence of Candida albicans by conventional and experimental antifungal drugs.

    PubMed

    Vuddhakul, V; McCormack, J G; Seow, W K; Smith, S E; Thong, Y H

    1988-06-01

    We tested the effects of antifungal drugs on adherence of Candida albicans in vitro. Significant reduction of adherence occurred after 2 h incubation with amphotericin B, nystatin, miconazole, econazole, ketoconazole, chlorohexidine and ICI 195,739. Significant inhibition of candida adherence by 5-fluorocytosine and amorolfin required 18 h incubation. Combinations of amphotericin B with 5-fluorocytosine, miconazole, ICI 195,739 and amorolfin resulted in synergistic inhibition of adherence. Adherence is an important pathogenic mechanism in candida infections and interference with this process may represent a major component of the mode of action of antifungal drugs. PMID:3045068

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

    PubMed

    Simić, A; Soković, M D; Ristić, M; Grujić-Jovanović, S; Vukojević, 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

  13. 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

  14. Growth and investigation of antifungal properties of ZnO nanorod arrays on the glass

    NASA Astrophysics Data System (ADS)

    Eskandari, M.; Haghighi, N.; Ahmadi, V.; Haghighi, F.; Mohammadi, SH. R.

    2011-01-01

    In this study, we have investigated the antifungal activity of ZnO nanorods prepared by the chemical solution method against Candida albicans. In the study, Zinc oxide nanorods have been deposited on glass substrates using the chemical solution method. The as-grown samples are characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). X-ray diffraction (XRD) showed zinc oxide nanorods grown in (0 0 2) orientation. The antifungal results indicated that ZnO nanorod arrays exhibit stable properties after two months and play an important role in the growth inhibitory of Candida albicans.

  15. The antibacterial and antifungal activity of a soda-lime glass containing silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Esteban-Tejeda, L.; Malpartida, F.; Esteban-Cubillo, A.; Pecharromán, C.; Moya, J. S.

    2009-02-01

    The antibacterial and antifungal activity of a low melting point soda-lime glass powder containing silver nanoparticles has been studied. Nano-Ag sepiolite fibres containing monodispersed silver nanoparticles (d50≈11 ± 9 nm) were used as the source of silver. This powder presents a high antibacterial (against gram-positive and gram-negative bacteria) as well as antifungal (against I. orientalis) activity. The observed high activity against yeast has been explained by considering the inhibitory effect of the Ca2+ lixiviated from the glass on the growth of the yeast colonies.

  16. 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

  17. The antifungal activity of corona treated polyamide and polyester fabrics loaded with silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Saponjic, Z.; Ilic, V.; Vodnik, V.; Mihailovic, D.; Jovancic, P.; Nedeljkovic, J.; Radetic, M.

    2008-07-01

    This study is aimed to highlight the possibility of using the corona treatment for fiber surface activation that can facilitate the loading of silver nanoparticles from colloids onto the polyester and polyamide fabrics and thus enhance their antifungal activity against Candida albicans. Additionally, the laundering durability of achieved effects was studied. Corona activated polyamide and polyester fabrics loaded with silver nanoparticles showed better antifungal properties compared to untreated fabrics. The positive effect of corona treatment became even more prominent after 5 washing cycles, especially for polyester fabrics.

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

    PubMed

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

    1983-05-01

    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

  19. 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

  20. The contribution of Aspergillus fumigatus stress responses to virulence and antifungal resistance.

    PubMed

    Brown, Neil A; Goldman, Gustavo H

    2016-03-01

    Invasive aspergillosis has emerged as one of the most common life-threatening fungal disease of humans. The emergence of antifungal resistant pathogens represents a current and increasing threat to society. In turn, new strategies to combat fungal infection are urgently required. Fungal adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. Here, we review the latest information on the signalling pathways in Aspergillus fumigatus that contribute to stress adaptations and virulence, while highlighting their potential as targets for the development of novel combinational antifungal therapies. PMID:26920884

  1. 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 Patrcia; Sangalli-Leite, Fernanda; de Oliveira, Haroldo Cesar; da Silva, Julhiany de Ftima; Rossi, Sulen Andrea; Benaducci, Tatiane; Wolf, Vanessa Gonalves; Regasini, Luis Octvio; Petrnio, Maicon Segalla; Silva, Dulce Helena Siqueira; Bolzani, Vanderlan S.; Mendes-Giannini, Maria Jos 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

  2. Salvage therapy with topical antifungal for Aspergillus fumigatus empyema complicating extrapleural pneumonectomy

    PubMed Central

    Purohit, Manoj; Guleri, Achyut; Zacharias, Joseph

    2012-01-01

    We describe an unusual case of Aspergillus fumigatus empyema and bronchopleural fistulae after extrapleural pneumonectomy (EPP) and chemoradiotherapy (CRT), which was treated successfully under salvage conditions with debridement, an innovative topical antifungal application and supplemented systemic antifungal therapy and which went on for a definitive surgical procedure. Combinations of CRT and EPP have been recommended in a select group of patients with malignant mesothelioma. Irrespective of the combination, EPP is associated with mortality in the range of 4–15% and a complication rate as high as 62%. PMID:22617507

  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. 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.

  5. 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

  6. In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum

    PubMed Central

    Tsuchimori, Noboru; Hayashi, Ryogo; Kitamoto, Naomi; Asai, Kentaro; Kitazaki, Tomoyuki; Iizawa, Yuji; Itoh, Katsumi; Okonogi, Kenji

    2002-01-01

    TAK-456 is a novel oral triazole compound with potent and broad-spectrum in vitro antifungal activity and strong in vivo efficacy against Candida albicans and Aspergillus fumigatus. TAK-456 inhibited sterol synthesis of C. albicans and A. fumigatus by 50% at 3 to 11 ng/ml. TAK-456 showed strong in vitro activity against clinical isolates of Candida spp., Aspergillus spp., and Cryptococcus neoformans, except for Candida glabrata. The MICs at which 90% of the isolates tested were inhibited byTAK-456, fluconazole, itraconazole, voriconazole, and amphotericin B were 0.25, 4, 0.5, 0.13, and 0.5 μg/ml, respectively, for clinical isolates of C. albicans and 1, >64, 0.5, 0.5, and 0.5 μg/ml, respectively, for clinical isolates of A. fumigatus. Therapeutic activities of TAK-456 and reference triazoles against systemic lethal infections caused by C. albicans and A. fumigatus in mice were investigated by orally administering drugs once daily for 5 days, and efficacies of the compounds were evaluated by the prolongation of survival. In normal mice, TAK-456 and fluconazole were effective against infection caused by fluconazole-susceptible C. albicans at a dose of 1 mg/kg. In transiently neutropenic mice, therapeutic activity of TAK-456 at 1 mg/kg of body weight against infection with the same strain was stronger than those at 1 mg/kg of fluconazole. TAK-456 was effective against infections with two strains of fluconazole-resistant C. albicans at a dose of 10 mg/kg. TAK-456 also expressed activities similar to or higher than those of itraconazole against the infections caused by two strains of A. fumigatus in neutropenic mice at a dose of 10 mg/kg. These results suggest that TAK-456 is a promising candidate for development for the treatment of candidiasis and aspergillosis in humans. PMID:11959573

  7. 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; Carrasco Juárez, María B; Sampietro, Diego A; Ben Altabef, Aida; 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

  8. 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±0.6μg/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±0.4μg/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

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

    PubMed Central

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

    2016-01-01

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

  10. Application of antifungal CFB to increase the durability of cement mortar.

    PubMed

    Park, Jong-Myong; Park, Sung-Jin; Kim, Wha-Jung; Ghim, Sa-Youl

    2012-07-01

    Antifungal cement mortar or microbiological calcium carbonate precipitation on cement surface has been investigated as functional concrete research. However, these research concepts have never been fused with each other. In this study, we introduced the antifungal calciteforming bacteria (CFB) Bacillus aryabhattai KNUC205, isolated from an urban tunnel (Daegu, South Korea). The major fungal deteriogens in urban tunnel, Cladosporium sphaerospermum KNUC253, was used as a sensitive fungal strain. B. aryabhattai KNUC205 showed CaCO3 precipitation on B4 medium. Cracked cement mortar pastes were made and neutralized by modified methods. Subsequently, the mixture of B. aryabhattai KNUC205, conidiospore of C. sphaerospermum KNUC253, and B4 agar was applied to cement cracks and incubated at 18 degrees C for 16 days. B. aryabhattai KNUC205 showed fungal growth inhibition against C. sphaerospermum. Furthermore, B. aryabhattai KNUC205 showed crack remediation ability and water permeability reduction of cement mortar pastes. Taken together, these results suggest that the CaCO3 precipitation and antifungal properties of B. aryabhattai KNUC205 could be used as an effective sealing or coating material that can also prevent deteriorative fungal growth. This study is the first application and evaluation research that incorporates calcite formation with antifungal capabilities of microorganisms for an environment-friendly and more effective protection of cement materials. In this research, the conception of microbial construction materials was expanded. PMID:22580322

  11. Adverse interactions between antifungal azoles and vincristine: review and analysis of cases.

    PubMed

    Moriyama, Brad; Henning, Stacey A; Leung, Janice; Falade-Nwulia, Oluwaseun; Jarosinski, Paul; Penzak, Scott R; Walsh, Thomas J

    2012-07-01

    Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.3-68 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life-threatening drug interaction. PMID:22126626

  12. 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

  13. 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...

  14. Synthesis and antifungal evaluation of (1,2,3-triazol-4-yl)methyl nicotinate chitosan.

    PubMed

    Qin, Yukun; Liu, Song; Xing, Ronge; Li, Kecheng; Yu, Huahua; Li, Pengcheng

    2013-10-01

    With an aim to discover novel chitosan derivatives with significant activities against crop-threatening fungi, (1,2,3-triazol-4-yl)methyl nicotinate chitosan (TAMNCS) was prepared via azide-alkyne click reaction. Its structure was characterized by FT-IR, (1)H NMR, elemental analysis, DSC, and SEM. In vitro antifungal properties of TAMNCS against Rhizoctonia solani Kühn (R. solani), Stemphylium solani weber (S. solani), and Alternaria porri (A. porri) were studied at the concentrations ranged from 0.25 mg/mL to 1.0 mg/mL. Experiments conducted displayed the derivative had obviously enhanced antifungal activity after chemical modification compared with original chitosan. Moreover, it was shown that TAMNCS can 94.2% inhibit growth of A. porri at 1.0 mg/mL, while dose at which the fungicide triadimefon had lower inhibitory index (62.2%). The primary antifungal results described here indicate this derivative may be a promising candidate as an antifungal agent. PMID:23732332

  15. Effect of antifungal agents on biological fitness of Lygus hesperus (Heteroptera: Miridae).

    PubMed

    Alverson, Janet; Cohen, Allen C

    2002-04-01

    Artificial diets have become important components of rearing systems for insects that are used for research purposes and in commercial production. Because the rearing conditions for insects also provide ideal settings for mold growth, antifungal additives are often used to reduce diet contamination. However, the antifungal agents must not only be effective in mold suppression, they must also be safe to the target insects of the rearing programs. The toxicity of five commonly used antifungal agents (benzoic acid, formalin, methyl paraben, propionic acid, and sorbic acid) was tested using diet bioassays on Lygus hesperus Knight, and the effect on biological fitness was measured. Biological fitness was defined as total number of survivors, mean biomass (dry weight) accumulated per cage over the total treatment period, egg production, time to adult emergence, and time to start of egg laying. Methyl paraben and formalin were found to have significant negative effects on these measurements of biological fitness. Challenge tests to determine the ability of the antifungal agents to suppress mold growth when inoculated into the diet medium are currently in progress. PMID:12019998

  16. Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones.

    PubMed

    Malik, Maqsood Ahmad; Al-Thabaiti, Shaeel Ahmed; Malik, Manzoor A

    2012-01-01

    Azoles are generally fungistatic, and resistance to fluconazole is emerging in several fungal pathogens. In an attempt to find novel azole antifungal agents with improved activity, a series of tetrazole ring bearing acylhydrazone derivatives were synthesized and screened for their in vitro antifungal activity. The mechanism of their antifungal activity was assessed by studying their effect on the plasma membrane using flow cytometry and determination of the levels of ergosterol, a fungal-specific sterol. Propidium iodide rapidly penetrated a majority of yeast cells when they were treated with the synthesized compounds at concentrations just above MIC, implying that fungicidal activity resulted from extensive lesions of the plasma membrane. Target compounds also caused a considerable reduction in the amount of ergosterol. The results also showed that the presence and position of different substituents on the phenyl ring of the acylhydrazone pendant seem to play a role on the antifungal activity as well as in deciding the fungistatic and fungicidal nature of the compounds. PMID:23109826

  17. 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...

  18. Two new flavonoids from Artemisa sacrorum Ledeb and their antifungal activity

    NASA Astrophysics Data System (ADS)

    Wang, Qing-Hu; Wu, Jie-si; Wu, Rong-jun; Han, Na-ren-chao-ke-tu; Dai, Na-yin-tai

    2015-05-01

    Two new flavonoids, named as sacriflavone A (1) and sacriflavone B (2), were isolated from the CHCl3 extract of Artemisa sacrorum Ledeb (A. sacrorum). The structures of the isolated compounds have been elucidated unambiguously by UV, MS, and a series of 1D and 2D NMR analyses. The isolated compounds exhibited antifungal activity against different Fusarium oxysporum f. sp. dianthi pathotypes.

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

    PubMed Central

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

    2011-01-01

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

  20. 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

  1. 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...

  2. Wasalexins A and B, new phytoalexins from wasabi: isolation, synthesis, and antifungal activity.

    PubMed

    Pedras, M S; Sorensen, J L; Okanga, F I; Zaharia, I L

    1999-10-18

    The chemical structure determination of two phytoalexins from wasabi (Wasabia japonica, syn. Eutrema wasabi), a plant resistant to virulent isolates of the blackleg fungus [Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode ex Fr.) Desm.], as well as their synthesis and antifungal activity towards isolates of P. lingam and P. wasabiae is reported. PMID:10571166

  3. 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 ...

  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. Induction of hepatocellular carcinomas in the Egyptian toad Bufo regularis by an antifungal drug (griseofulvin).

    PubMed

    el-Mofty, M M; Khudoley, V V; Essawy, A E; Abdel-Kerim, H M

    1993-01-01

    Neoplastic lesions (hepatocellular carcinomas) were induced in the liver in 18 of 100 experimental toads (Bufo regularis) force fed with the antifungal drug griseofulvin, at a dose level of 0.4 mg/50 g every day. Maximal time of exposure and observation was 12 weeks. The first tumors appeared in 2 male toads 4 weeks after the initiation of feeding. PMID:8497379

  6. Investigating the antifungal activity of TiO2 nanoparticles deposited on branched carbon nanotube arrays

    NASA Astrophysics Data System (ADS)

    Darbari, S.; Abdi, Y.; Haghighi, F.; Mohajerzadeh, S.; Haghighi, N.

    2011-06-01

    Branched carbon nanotube (CNT) arrays were synthesized by plasma-enhanced chemical vapour deposition on a silicon substrate. Ni was used as the catalyst and played an important role in the realization of branches in vertically aligned nanotubes. TiO2 nanoparticles on the branched CNTs were produced by atmospheric pressure chemical vapour deposition followed by a 500 °C annealing step. Transmission and scanning electron microscopic techniques were used to study the morphology of the TiO2/branched CNT structures while x-ray diffraction and Raman spectroscopy were used to verify the characteristics of the prepared nanostructures. Their antifungal effect on Candida albicans biofilms under visible light was investigated and compared with the activity of TiO2/CNT arrays and thin films of TiO2. The TiO2/branched CNTs showed a highly improved photocatalytic antifungal activity in comparison with the TiO2/CNTs and TiO2 film. The excellent visible light-induced photocatalytic antifungal activity of the TiO2/branched CNTs was attributed to the generation of electron-hole pairs by visible light excitation with a low recombination rate, in addition to the high surface area provided for the interaction between the cells and the nanostructures. Scanning electron microscopy was used to observe the resulting morphological changes in the cell body of the biofilms existing on the antifungal samples.

  7. Grafting β-Cyclodextrins to Silicone, Formulation of Emulsions and Encapsulation of Antifungal Drug

    NASA Astrophysics Data System (ADS)

    Noomen, Ahlem; Penciu, Alexandra; Hbaieb, Souhaira; Parrot-Lopez, Hélène; Amdouni, Noureddine; Chevalier, Yves; Kalfat, Rafik

    Emulsions of silicone polymers having β-cyclodextrin units as lateral chains have been prepared and used for the encapsulation of the antifungal drug griseofulvin. Such technology enables the formulation of active substances that are not soluble in water as dosage forms for topical administration.

  8. Active Internalization of the Penicillium chrysogenum Antifungal Protein PAF in Sensitive Aspergilli

    PubMed Central

    Oberparleiter, Christoph; Kaiserer, Lydia; Haas, Hubertus; Ladurner, Peter; Andratsch, Manfred; Marx, Florentine

    2003-01-01

    The Penicillium chrysogenum antifungal protein PAF inhibits the growth of various filamentous fungi. In this study, PAF was found to localize to the cytoplasm of sensitive aspergilli by indirect immunofluorescence staining. The internalization process required active metabolism and ATP and was prevented by latrunculin B, suggesting an endocytotic mechanism. PMID:14576124

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

    PubMed

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

    2016-01-01

    The aim of this paper is to identify and investigate an endophytic fungus (strain 28) that was isolated from Houttuynia cordata Thunb, a famous and widely-used Traditional Chinese Medicine. Based on morphological methods and a phylogenetic analysis of ITS sequences, this strain was identified as Chaetomium globosum. An antifungal activity bioassay demonstrated that the crude ethyl acetate (EtOAc) extracts of strain 28 had a wide antifungal spectrum and strong antimicrobial activity, particularly against Exserohilum turcicum (Pass.) Leonard et Suggs, Botrytis cinerea persoon and Botrytis cinerea Pers. ex Fr. Furthermore, the fermentation conditions, extraction method and the heat stability of antifungal substances from strain 28 were also studied. The results showed that optimal antifungal activity can be obtained with the following parameters: using potato dextrose broth (PDB) as the base culture medium, fermentation for 4-8d (initial pH: 7.5), followed by extraction with EtOAc. The extract was stable at temperatures up to 80°C. This is the first report on the isolation of endophytic C. globosum from H. cordata to identify potential alternative biocontrol agents that could provide new opportunities for practical applications involving H. cordata. PMID:26991297

  10. 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...

  11. Purification, characterization, and molecular gene cloning of an antifungal protein from Ginkgo biloba seeds.

    PubMed

    Sawano, Yoriko; Miyakawa, Takuya; Yamazaki, Hiroshi; Tanokura, Masaru; Hatano, Ken-ichi

    2007-03-01

    A novel basic protein with antifungal activity was isolated from the seeds of Ginkgo biloba and purified to homogeneity. The protein inhibited the growth of some fungi (Fusarium oxysporum, Trichoderma reesei, and Candida albicans) but did not exhibit antibacterial action against Escherichia coli. Furthermore, this protein showed weak inhibitory activity against the aspartic protease pepsin. To design primers for gene amplification, the NH(2)-terminal and partial internal amino acid sequences were determined using peptides obtained from a tryptic digest of the oxidized protein. The full-length cDNA of the antifungal protein was cloned and sequenced by RT-PCR and rapid amplification of cDNA ends (RACE). The cDNA contained a 402-bp open reading frame encoding a 134-aa protein with a potential signal peptide (26 residues), suggesting that this protein is synthesized as a preprotein and secreted outside the cells. The antifungal protein shows approximately 85% identity with embryo-abundant proteins from Picea abies and Picea glauca at the amino acid level; however, there is no homology between this protein and other plant antifungal proteins, such as defensin, and cyclophilin-, miraculin- and thaumatin-like proteins. PMID:17338634

  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. Addition of DNase Improves the In Vitro Activity of Antifungal Drugs against Candida albicans Biofilms

    PubMed Central

    Martins, Margarida; Henriques, Mariana; Lopez-Ribot, Jos L.; Oliveira, Rosrio

    2011-01-01

    SUMMARY Background Cells within Candida albicans biofilms display decreased susceptibility to most clinically used antifungal agents. We recently demonstrated that extracellular DNA (eDNA) plays an important role in biofilm integrity, as a component of the biofilm matrix. Objective To gain insight into the contributions of eDNA to C. albicans biofilms antifungal susceptibility by the investigation of the impact of the combined use of deoxyribonuclease I (DNase) and antifungals to treat biofilms. Methods C. albicans biofilms were formed using a simple and reproducible 96-well plate-based method. The activity of the combined use of 0.13 mg l?1 DNase and antifungals was estimated by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay, and total viable counts. Results and Conclusions Here we report the improved efficacy of amphotericin B when in combination with DNase against C. albicans biofilms, as assessed by XTT readings and viable counts. Furthermore, although DNase increased the efficacy of caspofungin in the reduction of mitochondrial activity, no changes were observed in terms of culturable cells. DNase did not affect biofilm cells susceptibility to fluconazole. This work suggests that agents that target processes affecting the biofilm structural integrity may have potential use as adjuvants of a catheterlock therapy. PMID:21668524

  14. In vitro activities of eight antifungal drugs against 104 environmental and clinical isolates of Aureobasidium pullulans.

    PubMed

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

    2014-09-01

    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 μg/ml) and had high MICs of voriconazole, isavuconazole, caspofungin, and micafungin. PMID:25001309

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

    PubMed

    Carrillo-Muñoz, 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

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

    PubMed Central

    Yao, Limin; Wan, Zhe; Li, Ruoyu

    2015-01-01

    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

  17. 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...

  18. 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 α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria. PMID:26474830

  19. Synthesis of a novel series of fluoroarene derivatives of artemisinin as potent antifungal and anticancer agent.

    PubMed

    Buragohain, Pori; Surineni, Naresh; Barua, Nabin C; Bhuyan, Purnajyoti D; Boruah, Paran; Borah, Jagat C; Laisharm, Surbala; Moirangthem, Dinesh Singh

    2015-08-15

    A series of new fluoroarene derivatives of artemisinin were prepared using Suzuki and Sonogashira cross-coupling reactions. An antifungal and antitumor activity was evaluated against opportunistic pathogen Fusarium oxysporum and Hela cancer cell line. All these derivatives have shown moderate to good activity. PMID:26099535

  20. Sequential and Structural Aspects of Antifungal Peptides from Animals, Bacteria and Fungi Based on Bioinformatics Tools.

    PubMed

    Neelabh; Singh, Karuna; Rani, Jyoti

    2016-06-01

    Emerging drug resistance varieties and hyper-virulent strains of microorganisms have compelled the scientific fraternity to develop more potent and less harmful therapeutics. Antimicrobial peptides could be one of such therapeutics. This review is an attempt to explore antifungal peptides naturally produced by prokaryotes as well as eukaryotes. They are components of innate immune system providing first line of defence against microbial attacks, especially in eukaryotes. The present article concentrates on types, structures, sources and mode of action of gene-encoded antifungal peptides such as mammalian defensins, protegrins, tritrpticins, histatins, lactoferricins, antifungal peptides derived from birds, amphibians, insects, fungi, bacteria and their synthetic analogues such as pexiganan, omiganan, echinocandins and Novexatin. In silico drug designing, a major revolution in the area of therapeutics, facilitates drug development by exploiting different bioinformatics tools. With this view, bioinformatics tools were used to visualize the structural details of antifungal peptides and to predict their level of similarity. Current practices and recent developments in this area have also been discussed briefly. PMID:27060002