Biology subjects

Kordalewska, M.

Publications and source records attributed to Kordalewska, M..

3 recordsLinked to original sources

bioRxiv2023

Novel non hot spot modification in Fks1 of Candida auris confers echinocandin resistance

We determined echinocandin susceptibility and FKS1 genotypes of thirteen clinical isolates of Candida auris recovered from four patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant and harbored a novel FKS1 mutation leading to an amino acid change W691L located downstream from hot-spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (ANF 16-32x; CAS >64x; MCF >64x).

microbiology↗

bioRxiv2021

Rare modification in the ergosterol biosynthesis pathway leads to amphotericin B resistance in Candida auris clinical isolates

We determined amphotericin B (AmB) susceptibility and sequenced key genes of the ergosterol biosynthesis pathway implicated in AmB resistance (ERG2, ERG3, ERG6, ERG11) of 321 clinical isolates of Candida auris. In antifungal susceptibility testing, 19 (5.9%) isolates were categorized as AmB-resistant (MIC [≥]2 mg/l). Only one AmB-resistant isolate presented a unique non-wild-type ERG6 genotype that was confirmed to confer amphotericin B resistance (MIC >32 mg/l) when introduced into a susceptible strain (MIC = 0.5 mg/l).

microbiology↗

bioRxiv2021

Impact of Erg11 amino acid substitutions identified in Candida auris clade III isolates on triazole drug susceptibility

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar, yet diminished pattern of reduced susceptibility was observed with long-tailed triazoles posaconazole and itraconazole for V125A/F126L, F126L, Y132F, and K143R alleles.

microbiology↗