Comparative Analysis of Two Candida parapsilosis Isolates Originating from the Same Patient Harbouring the Y132F and R398I Mutations in the ERG11 Gene

Cells. 2023 Jun 7;12(12):1579. doi: 10.3390/cells12121579.

Abstract

This work presents a comparative analysis of two clinical isolates of C. parapsilosis, isolated from haemoculture (HC) and central venous catheter (CVC). Both strains harboured Y132F and R398I mutations in the gene ERG11 associated with resistance to fluconazole (FLC). Differences between the HC and CVC isolates were addressed in terms of virulence, resistance to FLC, and lipid distribution. Expression of the ERG6 and ERG9 genes, lipid analysis, fatty acid composition, and lipase activity were assessed via qPCR, thin-layer chromatography/high-performance liquid chromatography, gas chromatography, and spectrophotometry, respectively. Regulation of the ERG6 and ERG9 genes did not prove any impact on FLC resistance. Analysis of lipid metabolism showed a higher accumulation of lanosterol in both the isolates regardless of FLC presence. Additionally, a decreased level of triacylglycerols (TAG) with an impact on the composition of total fatty acids (FA) was observed for both isolates. The direct impact of the ERG11 mutations on lipid/FA analysis has not been confirmed. The higher lipase activity observed for C. parapsilosis HC isolate could be correlated with the significantly decreased level of TAG. The very close relatedness between both the isolates suggests that one isolate was derived from another after the initial infection of the host.

Keywords: Candida parapsilosis; ERG genes; fatty acids; lipase activity; lipid analysis; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Candida parapsilosis* / genetics
  • Drug Resistance, Fungal / genetics
  • Fluconazole
  • Humans
  • Lipase / genetics
  • Lipids
  • Microbial Sensitivity Tests
  • Mutation / genetics

Substances

  • Antifungal Agents
  • Fluconazole
  • Lipase
  • Lipids

Grants and funding

This research was funded by the Slovak Research and Development Agency under contracts of SK-PT-18-0006 as part of the Bilateral Cooperation Program (2019–2022), APVV-21-0302 and grant VEGA 2/0036/22 from the Ministry of Education, Science, Research, and the Sport of the Slovak Republic.