Biology subjects

Mikulski, T. D.

Publications and source records attributed to Mikulski, T. D..

2 recordsLinked to original sources

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↗