Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing

Clinics (Sao Paulo). 2024 Sep 15:79:100497. doi: 10.1016/j.clinsp.2024.100497. eCollection 2024.

Abstract

Introduction: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing.

Method: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance.

Results: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1.

Discussion: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.

Keywords: Candida auris; Fluconazole resistance; Genomic; Molecular docking; Virulence.

MeSH terms

  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Asia, Southern
  • Beijing
  • Candida auris* / drug effects
  • Candida auris* / genetics
  • Candida auris* / pathogenicity
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Drug Resistance, Fungal* / genetics
  • Fluconazole* / pharmacology
  • Fluconazole* / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Mutation
  • Virulence / genetics
  • Whole Genome Sequencing

Substances

  • Antifungal Agents
  • Fluconazole