We determined the susceptibility to oxidative stress and assessed the four virulence factors of the 38 Candida glabrata clinical isolates originating from two teaching hospitals in Slovakia. All the isolates were susceptible to hydrogen peroxide, diamide, and 7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine (CTBT) inducing an increased formation of reactive oxygen species in fungal cells. The mean relative cell surface hydrophobicity (CSH) of isolates was 21.9, ranging from 1.92 to 56.96. All isolates showed biofilm formation. A high biofilm formation was observed among 60.5% of isolates. Positive correlations were observed between biofilm formation and moderate values of CSHs. The 76.3% and 84.2% of isolates displayed varying degrees of proteinase and phospholipase activity, respectively. These results demonstrate a differential distribution of factors contributing to virulence of C. glabrata clinical isolates and point to their significance in pathogenesis that would be targeted by novel antifungals.

• MeSH
• Biofilms growth & development   MeSH
• Candida glabrata drug effects   isolation & purification   pathogenicity   physiology   MeSH
• Diamide toxicity   MeSH
• Virulence Factors metabolism   MeSH
• Phospholipases metabolism   MeSH
• Stress, Physiological * MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Candidiasis microbiology   MeSH
• Humans MeSH
• Hospitals, Teaching MeSH
• Oxidative Stress * MeSH
• Oxidants toxicity   MeSH
• Hydrogen Peroxide toxicity   MeSH
• Peptide Hydrolases metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Triazines toxicity   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Slovakia MeSH
• Names of Substances
• 7-chlorotetrazolo(5,1-c)benzo(1,2,4)triazine MeSH Browser
• Diamide MeSH
• Virulence Factors MeSH
• Phospholipases MeSH
• Oxidants MeSH
• Hydrogen Peroxide MeSH
• Peptide Hydrolases MeSH
• Reactive Oxygen Species MeSH
• Triazines MeSH

The pel1 mutation in Saccharomyces cerevisiae and the Cgpgs1Delta mutation in Candida glabrata result in deficiency of mitochondrial phosphatidylglycerolphosphate synthase and lack of two anionic phospholipids, phosphatidylglycerol and cardiolipin. DNA sequence analysis of the PCR-amplified pel1 mutant allele revealed that the pel1 mutation resulted from a single amino-acid substitution (Glu(463)Lys) in the C-terminal part of encoded enzyme. The CgPGS1 gene cloned in a centromeric pFL38 vector functionally complemented the pel1 mutation in S. cerevisiae. Likewise, the ScPGS1 gene cloned in pCgACU5 plasmid fully complemented the Cgpgs1Delta mutation in C. glabrata. This mutation increased the cell surface hydrophobicity and decreased biofilm formation. These results support a close evolutionary relatedness of S. cerevisiae and C. glabrata and point to the relationship between expression of virulence factors and anionic phospholipid deficiency in pathogenic C. glabrata.

• MeSH
• Biofilms MeSH
• Phenotype MeSH
• Phospholipids chemistry   deficiency   MeSH
• Fungal Proteins chemistry   genetics   metabolism   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Yeasts chemistry   classification   genetics   physiology   MeSH
• Molecular Sequence Data MeSH
• Mutation * MeSH
• Amino Acid Sequence MeSH
• Sequence Alignment MeSH
• Transferases (Other Substituted Phosphate Groups) chemistry   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase MeSH Browser
• Phospholipids MeSH
• Fungal Proteins MeSH
• Transferases (Other Substituted Phosphate Groups) MeSH

The regulation of gene transcription allows yeast cells to respond properly to changing environmental conditions. Several protein complexes take part in this process. They involve RNA polymerase complexes, chromatin remodeling complexes, mediators, general transcription factors and specific transcriptional regulators. Using Saccharomyces cerevisiae as reference, the genomes of six species (Ashbya gossypii, Kluyveromyces lactis, K. waltii, Candida albicans, C. glabrata and Schizosaccharomyces pombe) that are human pathogens or important for the food industry were analyzed for their complement of genes encoding the homologous transcriptional regulators. The number of orthologs identified in a given species correlated with its phylogenetic distance from S. cerevisiae. Many duplicated genes encoding transcriptional regulators in S. cerevisiae and C. glabrata were reduced to one copy in species diverged before the ancestral whole genome duplication. Some transcriptional regulators appear to be specific for S. cerevisiae and probably reflect the physiological differences among species. Phylogenetic analysis and conserved gene order relationships indicate that a similar set of gene families involved in the control of multidrug resistance and oxidative stress response already existed in the common ancestor of the compared fungal species.

• MeSH
• Drug Resistance, Fungal MeSH
• Fungal Proteins chemistry   genetics   metabolism   MeSH
• Phylogeny MeSH
• Transcription, Genetic * MeSH
• Genome, Fungal * MeSH
• Yeasts chemistry   classification   genetics   metabolism   MeSH
• Molecular Sequence Data MeSH
• Gene Expression Regulation, Fungal MeSH
• Amino Acid Sequence MeSH
• Transcription Factors chemistry   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Comparative Study MeSH
• Names of Substances
• Fungal Proteins MeSH
• Transcription Factors MeSH

Candidiases, infections caused by germination forms of the Candida fungus, represent a heterogeneous group of diseases from systemic infection, through mucocutaneous form, to vulvovaginal form. Although caused by one organism, each form is controlled by distinct host immune mechanisms. Phagocytosis by polymorphonuclears and macrophages is generally accepted as the host immune mechanism for Candida elimination. Phagocytes require proinflammatory cytokine stimulation which could be harmful and must be regulated during the course of infection by the activity of CD8+ and CD4+ T cells. In the vaginal tissue the phagocytes are inefficient and inflammation is generally an unwanted reaction because it could damage mucosal tissue and break the tolerance to common vagina antigens including the otherwise saprophyting Candida yeast. Recurrent form of vulvovaginal candidiasis is probably associated with breaking of such tolerance. Beside the phagocytosis, specific antibodies, complement, and mucosal epithelial cell comprise Candida eliminating immune mechanisms. They are regulated by CD4+ and CD8+ T cells which produce cytokines IL-12, IFN-gamma, IL-10, TGF-beta, etc. as the response to signals from dendritic cells specialized to sense actual Candida morphotypes. During the course of Candida infection proinflammatory signals (if initially necessary) are replaced successively by antiinflammatory signals. This balance is absolutely distinct during each candidiasis form and it is crucial to describe and understand the basic principles before designing new therapeutic and/or preventive approaches.

• MeSH
• Antifungal Agents therapeutic use   MeSH
• Immunity, Cellular MeSH
• Candida classification   immunology   pathogenicity   MeSH
• Phagocytosis MeSH
• Candidiasis drug therapy   immunology   MeSH
• Humans MeSH
• Carrier State immunology   MeSH
• Immunity, Innate immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Antifungal Agents MeSH

The influence of subinhibitory concentrations of six established and 19 newly synthesized antifungal compounds on the dimorphic transition of three C. albicans strains was evaluated in the filamentation-inducing medium. Amphotericin B was found to produce almost complete inhibition in the germination at a concentration of 1/10 of the corresponding MIC and partial inhibition at a concentration as low as MIC/50. Flucytosine and four azole derivatives were proven ineffective. From the newly synthesized drugs, the incrustoporin derivative LNO6-22, two phenylguanidine derivatives (PG15, PG45), and four thiosalicylanilide derivatives, in particular, showed results comparable to those of amphotericin B, with a high inhibition of germ tube formation at concentrations of MIC/10. In general, concentrations of MIC/50 had no visible effect.

• MeSH
• Amphotericin B pharmacology   MeSH
• Antifungal Agents chemical synthesis   chemistry   pharmacology   MeSH
• Candida albicans drug effects   growth & development   MeSH
• 4-Butyrolactone analogs & derivatives   chemical synthesis   chemistry   pharmacology   MeSH
• Guanidines chemical synthesis   chemistry   pharmacology   MeSH
• Microbial Sensitivity Tests methods   standards   MeSH
• Morphogenesis drug effects   MeSH
• Salicylates chemical synthesis   chemistry   pharmacology   MeSH
• Sulfhydryl Compounds chemical synthesis   chemistry   pharmacology   MeSH
• Dose-Response Relationship, Drug MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amphotericin B MeSH
• Antifungal Agents MeSH
• 4-Butyrolactone MeSH
• Guanidines MeSH
• incrustoporin MeSH Browser
• phenylguanidine MeSH Browser
• Salicylates MeSH
• Sulfhydryl Compounds MeSH
• thiosalicylic acid MeSH Browser

Decreased susceptibility of K. lactis mutants impaired in the function of cytochrome c, cytochrome c1 and cytochrome-c oxidase to fluconazole, bifonazole and amphotericin B in comparison with the isogenic wild-type strain was observed. Flow cytometry with rhodamine 6G did not show any changes in the accumulation of the dye in the mutant cells compared with the corresponding wild-type strain. Sterol analysis showed similar overall amount of sterols in both wild-type and mutant cells. Taking into account the increased amphotericin B resistance and significantly diminished susceptibility of mutant cells to lyticase digestion, the cell wall structure and/or composition may probably be responsible for the observed changes in the susceptibility of mutants to the antifungal compounds used.

• MeSH
• Amphotericin B pharmacology   MeSH
• Antifungal Agents pharmacology   MeSH
• Cell Wall chemistry   drug effects   MeSH
• Glucan Endo-1,3-beta-D-Glucosidase metabolism   MeSH
• Drug Resistance, Fungal * MeSH
• Fungal Proteins genetics   metabolism   MeSH
• Kluyveromyces cytology   drug effects   genetics   physiology   MeSH
• Microbial Sensitivity Tests MeSH
• Mitochondria drug effects   genetics   physiology   MeSH
• Multienzyme Complexes metabolism   MeSH
• Mutation * MeSH
• Blotting, Northern MeSH
• Peptide Hydrolases metabolism   MeSH
• Flow Cytometry MeSH
• Sterols metabolism   MeSH
• Electron Transport drug effects   genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amphotericin B MeSH
• Antifungal Agents MeSH
• Glucan Endo-1,3-beta-D-Glucosidase MeSH
• Fungal Proteins MeSH
• lyticase MeSH Browser
• Multienzyme Complexes MeSH
• Peptide Hydrolases MeSH
• Sterols MeSH