Whole Genome Sequencing of a Clinical Drug Resistant Isolate Reveals Known and Novel Mutations in Genes Involved in Resistance Acquisition Mechanisms

Overview

Journal J Med Microbiol

Specialty Microbiology

Date 2021 Apr 28

PMID 33909551

Citations 5

Authors

Roy A Khalaf

Nour Fattouh

Matej Medvecky

Jaroslav Hrabak

Affiliations

Soon will be listed here.

Abstract

is an opportunistic pathogen accounting for the majority of cases of infections. Currently, 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 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 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 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.

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