Whole genome sequencing of a clinical drug resistant Candida albicans isolate reveals known and novel mutations in genes involved in resistance acquisition mechanisms
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu časopisecké články
PubMed
33909551
PubMed Central
PMC8289213
DOI
10.1099/jmm.0.001351
Knihovny.cz E-zdroje
- Klíčová slova
- Candida albicans, antifungal resistance, azoles, ergosterol, virulence, whole genome sequencing,
- MeSH
- azoly farmakologie MeSH
- bodová mutace MeSH
- Candida albicans chemie účinky léků genetika patogenita MeSH
- ergosterol analýza MeSH
- fenotyp MeSH
- fungální léková rezistence genetika MeSH
- genotyp MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- pilotní projekty MeSH
- sekvenování celého genomu * MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Libanon MeSH
- Názvy látek
- azoly MeSH
- ergosterol MeSH
Candida albicans is an opportunistic pathogen accounting for the majority of cases of Candida infections. Currently, C. albicans are developing resistance towards different classes of antifungal drugs and this has become a global health burden that does not spare Lebanon. This study aims at determining point mutations in genes known to be involved in resistance acquisition and correlating resistance to virulence and ergosterol content in the azole resistant C. albicans isolate CA77 from Lebanon. This pilot study is the first of its kind to be implemented in Lebanon. We carried out whole genome sequencing of the azole resistant C. albicans isolate CA77 and examined 18 genes involved in antifungal resistance. To correlate genotype to phenotype, we evaluated the virulence potential of this isolate by injecting it into BALB/c mice and we quantified membrane ergosterol. Whole genome sequencing revealed that eight out of 18 genes involved in antifungal resistance were mutated in previously reported and novel residues. These genotypic changes were associated with an increase in ergosterol content but no discrepancy in virulence potential was observed between our isolate and the susceptible C. albicans control strain SC5314. This suggests that antifungal resistance and virulence potential in this antifungal resistant isolate are not correlated and that resistance is a result of an increase in membrane ergosterol content and the occurrence of point mutations in genes involved in the ergosterol biosynthesis pathway.
Biomedical Center Faculty of Medicine in Pilsen Charles University 32300 Pilsen Czech Republic
Department of Natural Sciences Lebanese American University PO Box 36 Byblos Lebanon
Institute of Biodiversity Animal Health and Comparative Medicine University of Glasgow Glasgow UK
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