Microbial and chemical transformations of some 12,13-epoxytrichothec-9,10-enes.
Resting cells of Streptomyces griseus, Mucor mucedo, and a growing culture of Acinetobacter calcoaceticus when mixed with compounds related to 12,13-epoxytrichothec-9-ene-4beta,15-diacetoxy-3alpha-ol(anguidine) produced a series of derivatives that were either partially hydrolyzed or selectively acylated. These derivatives showed marked differences in activities as assayed by antifungal and tissue culture cytotoxicity tests. (+info)
Amphotericin B- and fluconazole-resistant Candida spp., Aspergillus fumigatus, and other newly emerging pathogenic fungi are susceptible to basic antifungal peptides.
The present study shows that a number of basic antifungal peptides, including human salivary histatin 5, a designed histatin analog designated dhvar4, and a peptide from frog skin, PGLa, are active against amphotericin B-resistant Candida albicans, Candida krusei, and Aspergillus fumigatus strains and against a fluconazole-resistant Candida glabrata isolate. (+info)
In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi.
The in-vitro fungistatic and fungicidal activities of voriconazole were compared with those of itraconazole and amphotericin B. MICs for 110 isolates belonging to 11 species of filamentous fungi were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the three antifungal agents were also determined. The MIC ranges of the three compounds were comparable for Aspergillus flavus, Aspergillus fumigatus, Cladophialophora bantiana and Exophiala dermatitidis. Voriconazole and itraconazole were more active than amphotericin B against Fonsecaea pedrosoi, but the two azole agents were less active against Sporothrix schenckii. Voriconazole was more active than itraconazole or amphotericin B against Scedosporium apiospermum, but less active than the other two agents against two mucoraceous moulds, Absidia corymbifera and Rhizopus arrhizus. Voriconazole and amphotericin B were more active than itraconazole against Fusarium solani. With the exception of S. apiospermum, all the moulds tested had MLC50 values of < or =2 mg/L and MLC90 values of < or =4 mg/L against amphotericin B. Voriconazole and itraconazole showed fungicidal effects against five of the 1 1 moulds tested (A. flavus, A. fumigatus, C. bantiana, E. dermatitidis and F. pedrosoi) with MLC90 values of < or =2 mg/L. In addition, voriconazole was fungicidal for Phialophora parasitica. Our results suggest that voriconazole could be effective against a wide range of mould infections in humans. (+info)
Novel genes induced during an arbuscular mycorrhizal (AM) symbiosis formed between Medicago truncatula and Glomus versiforme.
Many terrestrial plant species are able to form symbiotic associations with arbuscular mycorrhizal fungi. Here we have identified three cDNA clones representing genes whose expression is induced during the arbuscular mycorrhizal symbiosis formed between Medicago truncatula and an arbuscular mycorrhizal fungus, Glomus versiforme. The three clones represent M. truncatula genes and encode novel proteins: a xyloglucan endotransglycosylase-related protein, a putative arabinogalactan protein (AGP), and a putative homologue of the mammalian p110 subunit of initiation factor 3 (eIF3). These genes show little or no expression in M. truncatula roots prior to formation of the symbiosis and are significantly induced following colonization by G. versiforme. The genes are not induced in roots in response to increases in phosphate. This suggests that induction of expression during the symbiosis is due to the interaction with the fungus and is not a secondary effect of improved phosphate nutrition. In situ hybridization revealed that the putative AGP is expressed specifically in cortical cells containing arbuscules. The identification of two mycorrhiza-induced genes encoding proteins predicted to be involved in cell wall structure is consistent with previous electron microscopy data that indicated major alterations in the extracellular matrix of the cortical cells following colonization by mycorrhizal fungi. (+info)
Comparison of interferon-gamma, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens.
Proinflammatory cytokines have been proposed as adjunctive therapeutic agents to enhance the host immune response during infections caused by opportunistic fungi. The study compared the differential in vitro priming effects of interferon-gamma (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on hyphal damage of opportunistic fungi mediated by isolated neutrophils (polymorphonuclear leukocytes, PMNL) and buffy coat cells (polymorphonuclear leukocytes/peripheral blood mononuclear cells, PMNL/PBMC) from healthy donors. IFN-gamma (1000 U/mL) effectively primed both PMNL and PMNL/PBMC for enhanced hyphal damage of Aspergillus fumigatus, Fusarium solani, and Candida albicans. G-CSF (100 ng/mL) increased hyphal damage mediated by both PMNL and PMNL/PBMC against F. solani, and GM-CSF (100 ng/mL) augmented the antifungal activity of PMNL/PBMC against hyphal forms of both F. solani and C. albicans. IFN-gamma may be superior to G-CSF or GM-CSF for enhancing the microbicidal activity of PMNL and PMNL/PBMC against opportunistic fungi. (+info)
Contaminations occurring in fungal PCR assays.
Successful in vitro amplification of fungal DNA in clinical specimens has been reported recently. In a collaboration among five European centers, the frequency and risk of contamination due to airborne spore inoculation or carryover contamination in fungal PCR were analyzed. The identities of all contaminants were specified by cycle sequencing and GenBank analysis. Twelve of 150 PCR assays that together included over 2,800 samples were found to be contaminated (3.3% of the negative controls were contaminated during the DNA extraction, and 4.7% of the PCR mixtures were contaminated during the amplification process). Contaminants were specified as Aspergillus fumigatus, Saccharomyces cerevisiae, and Acremonium spp. Further analysis showed that commercially available products like zymolyase powder or 10x PCR buffer may contain fungal DNA. In conclusion, the risk of contamination is not higher in fungal PCR assays than in other diagnostic PCR-based assays if general precautions are taken. (+info)
Chemically defined medium for susceptibility testing of antimicrobial agents.
A defined medium was developed that supports growth of many of the bacterial and fungal pathogens frequently isolated in clinics. (+info)
Brasilicardin A, a new terpenoid antibiotic from pathogenic Nocardia brasiliensis: fermentation, isolation and biological activity.
A novel tricyclic diterpenoid antibiotic, brasilicardin A, was isolated from the culture broth of Nocardia brasiliensis IFM 0406. The antibiotic exhibited immunosuppressive activity in a mouse mixed lymphocyte reaction (MLR) assay system and its IC50 value was 0.057 microg/ml. Although the inhibitory activity of cyclosporin A (CyA) against IL-2 production was confirmed in the MLR assay system, brasilicardin A did not have the activity. The results of in vitro toxicity testing of brasilicardin A against various human cell lines were compared with those of CyA. (+info)