Antifungal drug resistance pattern of Candida. spp isolated from vaginitis in Ilam-Iran during 2013-2014

Vaginal Candidiasis is the most common and important opportunistic fungal infection in women. By increasing use of antifungal drugs in recent years, it has caused drug resistance. This study aims to evaluate antifungal drugs susceptibility of Candida. spp isolated of women with vaginitis from Ilam-Iran during 2013-2014. samples were collected and cultured from 385 women with vaginitis, then Candida.spp was diagnosed by standard method. Antifungal drug susceptibility test for nystatin 100 unit/disk, fluconazole 10µg/disk, itraconazole 10µg/disk, ketoconazole 10µg/disk, amphotericinB 20µg/disk, clotrimazole 10µg/disk, posaconazole 5µg/disk, and voriconazole 1µg/disk were carried out by M44-A method(CLSI). From all culture positive samples, 150 isolates were Candida albicans and 89 isolates were non-albicans. The resistance to fluconazole, itraconazole, ketoconazole, clotrimazole, voriconazole, posaconazole, nystatin and amphotericin B was 76%, 62%, 72%, 55%, 6%, 7%, 1% and 0%. The highest resistance was seen for fluconazole , itraconazole, and the highest susceptible was seen for nystatin and amphotericin B. These results indicate nystatin and amphotericin B can be used as the first line for empirical therapy of vaginal candidiasis in the district.     

念珠菌阴道炎及其耐药性分析

目的探索女性念珠菌阴道炎发病情况及耐药性。方法白带常规采用直接盐水涂片法;阴道分泌物培养按细菌培养常规法进行培养。结果白带常规检查中念珠菌阳性率为12．9％,滴虫阳性率为2．0％,线索细胞阳性率为10．3％,清洁度（Ⅲ～Ⅳ）为13．0％。阴道分泌物培养情况如下：念珠菌阳性率为26％,细菌感染阳性率为45％．今珠菌培养阳性的标本中：白色念珠菌占90％,光滑念珠菌占7．8％,热带念珠菌占2．2％。念珠菌药敏结果分析：制霉素敏感度大于80％,是治疗念珠菌阴道炎最理想的药物。结论念珠菌阴道炎处于逐年上升的趋势：医生应根据药敏结果合理选择抗真菌药物,以免抗生素的滥用。     

Glucosamine resistance in yeast

Summary Two cytoplasmic, glucosamine resistant (GR) mutants of Saccharomyces cerevisiae, GR6 and GR10, were crossed to strains bearing known mitochondrial markers. Analysis of vegetative and meiotic segregation patterns in these crosses suggested that the glucosamine resistance conferring factor did not reside on mitDNA. This was confirmed by ethidium bromide treatments which completely abolished oligomycin resistance due to a mitochondrial mutation at the OLI2 locus but which failed to eliminate the GR factor present in the same strain. Comparison of GR6 and GR10 to some other known cytoplasmic determinants suggested that while glucosamine resistance is not related to the killer plasmid it may be allelic to the URE3 determinant and/or to the PSI factor.     

Antifungal cellobiose lipid secreted by the epiphytic yeast Pseudozyma graminicola

The yeast Pseudozyma graminicola isolated from plants inhibited growth of almost all ascomycetes and basidiomycetes tested (over 270 species of ca. 100 genera) including pathogenic species. This yeast secreted a fungicidal agent, which was identified as a glycolipid composed of cellobiose residue with two O-substituents (acetyl and 3-hydroxycaproic acid) and 2,15,16-trihydroxypalmitic acid. The release of ATP from the glycolipid-treated cells indicated that this glycolipid impaired the permeability of the cytoplasmic membrane. Basidiomycetes were more sensitive to the cellobiose lipid than ascomycetes.     

Antifungal drug resistance in molds: Clinical and microbiological factors

The incidence of fungal infections has increased over the past decade. In addition to classical pathogens, such as Aspergillus spp, new fungal species are increasingly reported. Despite the availability of new antifungals, mortality of invasive fungal infections remains very high. The host immune status is the main factor for survival. However, most of these pathogens have high minimum inhibitory concentrations (MICs) to antifungals, and therefore, the influence of these high MICs in the outcome of the patients have begun to be addressed. Several strains of Aspergillus fumigatus showing resistance to itraconazole have been isolated, and the molecular-resistance mechanisms have been characterized. In addition, attempts to correlate high MICs with patient outcome have been performed. Although correlation is far from perfect, a clear trend between high MICs and poor outcome has been established. Resistance of fungi to antifungals is a health problem requiring support from research agencies.     

Membrane homoeostasis and multidrug resistance in yeast

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.     

Antifungal activity of organobismuth compounds against the yeast Saccharomyces cerevisiae: structure-activity relationship

Antifungal activity of organobismuth(III) and (V) compounds 1-9 was examined against the yeast, Saccharomyces cerevisiae. A clear structure-activity relationship was observed in these compounds. Thus, triarylbismuth dichlorides 2 [(4-YC6H4)3BiCl2: Y=MeO, F, Cl, CF3, CN, NO2] and halobismuthanes 6 [2-(t)BuSO2C6H4(4-YC6H4)BiX: Y=MeO, Me, H, Cl; X=Cl, Br, I], 7 [Bi(X)(C6H4-2-SO2C6H4-1'-): X=Cl, Br, I], 8 [2-Me2NCH2C6H4(Ph)BiX: X=Cl, Br] and 9 [4-MeC6H4(8-Me2NC10H6-1-)BiCl] showed the growth inhibition effect, while triarylbismuth difluorides 3 [(4-YC6H4)3BiF2] and triarylbismuthanes 1 [(4-YC6H4)3Bi], 4 [2-(t)BuSO2C6H4(4-YC6H4)2Bi] and 5 [4-YC6H4Bi(C6H4-2-SO2C6H4-1'-)] were not active at all irrespective of the nature of the substituents. Generation of the inhibition effect is governed by the facility of nucleophilic reaction at the bismuth center and the Lewis acidic bismuth center is an active site. Of all the bismuth compounds attempted, halobismuthanes 7 derived from diphenyl sulfone exhibited the highest activities. An X-ray crystallographic study of 7a [Bi(Cl)(C6H4-2-SO2C6H4-1'-)] revealed that the bismuth center adopts a seven-coordinated geometry, which is unusual in organobismuth(III) compounds, through the intramolecular and intermolecular coordination between the bismuth and oxygen atoms. The marked inhibition effect of 7 may be attributed to such a highly coordinated geometry, which allows the bismuth center to bind tightly with some biomolecules playing important roles in the growth of S. cerevisiae.