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
- biofilmy růst a vývoj MeSH
- Candida glabrata účinky léků izolace a purifikace patogenita fyziologie MeSH
- diamid toxicita MeSH
- faktory virulence metabolismus MeSH
- fosfolipasy metabolismus MeSH
- fyziologický stres MeSH
- hydrofobní a hydrofilní interakce MeSH
- kandidóza mikrobiologie MeSH
- lidé MeSH
- nemocnice fakultní MeSH
- oxidační stres MeSH
- oxidancia toxicita MeSH
- peroxid vodíku toxicita MeSH
- proteasy metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- triaziny toxicita MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- aktivace transkripce genetika MeSH
- cytoplazmatické struktury genetika MeSH
- financování organizované MeSH
- fyziologická adaptace MeSH
- fyziologický stres MeSH
- mechanický stres MeSH
- osmotický tlak fyziologie MeSH
- oxidační stres genetika MeSH
- Saccharomyces cerevisiae enzymologie fyziologie genetika MeSH
- signální transdukce fyziologie genetika MeSH
- xenobiotika metabolismus toxicita MeSH
V súčasnosti sa stáva čoraz viac problematickou terapia nielen bakteriálnych ale aj fungálnych infekcií. Väčšinou je to z dôvodu nadobudnutia mnohonásobnej rezistencie, ktorá sa vyskytuje od prokaryotických buniek až po bunky človeka. Fenotyp mnohonásobnej rezistencie predstavuje odpoveď buniek na prítomnosť cytotoxických látok v prostredí. Základným mechanizmom mnohonásobnej rezistencie je nadexpresia membránových proteínov vylučujúcich toxické látky von z bunky. Mechanizmus rezistencie založený na efluxe inhibítorov z bunky v dôsledku nadprodukcie transportných proteínov bol pozorovaný aj u niektorých patogénov rastlín, živočíchov a nádorových buniek človeka. Fenomén mnohonásobnej rezistencie, spojený s nadmerným a dlhodobým používaním antifungálnych látok, najmä azolových derivátov, sa potvrdil aj u kvasinky Candida glabrata, ktorá sa čoraz viac dostáva do pozornosti odbornej verejnosti. Znížená citlivosť predovšetkým na azolové deriváty, schopnosť rýchlej adaptácie na stresové podmienky a kombinácia viacerých mechanizmov rezistencie voči štrukturálne a funkčne nepríbuzným antifungálnym látkam predstavujú druh C. glabrata ako potenciálnu hrozbu najmä v nemocničných zariadeniach.
Treatment of not only bacterial but also fungal infections is currently a growing concern. A major reason is the acquisition of multidrug resistance in both prokaryotic and human cells. The multidrug resistance phenotype is a cellular response to the presence of cytotoxic substances in the environment. The basic mechanism of multidrug resistance is overexpression of the membrane proteins involved in the extrusion of toxic substances outside the cell. The resistance mechanism based on the efflux of inhibitors as a result of the overproduction of transport proteins was also observed in some plant and animal pathogens and human tumour cells. The phenomenon of multidrug resistance associated with an excessive and long-term use of antifungals, in particular of azole derivatives, was also confirmed in the yeast Candida glabrata which is becoming a growing concern for health care professionals. Reduced susceptibility to azole derivatives in particular, a high potential for adapting to stressors, and multiple mechanisms of resistance to structurally and functionally unrelated antifungal drugs make the species C. glabrata a potential threat to hospital patients.
- Klíčová slova
- faktory virulencie, mechanizmy rezistencie, biofilm, antimykotiká,
- MeSH
- antifungální látky farmakologie MeSH
- azoly farmakologie MeSH
- Candida glabrata fyziologie účinky léků MeSH
- lidé MeSH
- mnohočetná fungální léková rezistence fyziologie MeSH
- oportunní infekce mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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
- biofilmy MeSH
- fenotyp MeSH
- financování organizované MeSH
- fosfolipidy chemie nedostatek MeSH
- fungální proteiny genetika chemie metabolismus MeSH
- hydrofobní a hydrofilní interakce MeSH
- kvasinky MeSH
- molekulární sekvence - údaje MeSH
- mutace MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- transferasy pro jiné substituované fosfátové skupiny genetika chemie metabolismus 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
- fungální léková rezistence MeSH
- fungální proteiny genetika chemie metabolismus MeSH
- fylogeneze MeSH
- genetická transkripce MeSH
- genom fungální MeSH
- kvasinky MeSH
- molekulární sekvence - údaje MeSH
- regulace genové exprese u hub MeSH
- sekvence aminokyselin MeSH
- transkripční faktory genetika chemie metabolismus MeSH
- MeSH
- chemorezistence fyziologie MeSH
- farmakoterapie metody MeSH
- finanční podpora výzkumu jako téma MeSH
- membránové transportní proteiny antagonisté a inhibitory fyziologie MeSH
- mnohočetná bakteriální léková rezistence fyziologie MeSH
- mnohočetná fungální léková rezistence fyziologie MeSH
- regulace genové exprese genetika MeSH
- Publikační typ
- přehledy MeSH
