FKS2 and FKS3 genes of opportunistic human pathogen Candida albicans influence echinocandin susceptibility

Sumanun Suwunnakorn, Hironao Wakabayashi, Milena Kordalewska, David S. Perlin, Elena Rustchenko

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous FKS genes that are evolutionarily conserved. One of these, the essential gene FKS1, encodes the catalytic subunit of glucan synthase, which is the target of echinocandin drugs and also serves as a site of drug resistance. The other two glucan synthase-encoding genes, FKS2 and FKS3, are also expressed, but their roles in resistance are considered unimportant. However, we report here that expression of FKS1 is upregulated in strains lacking either FKS2 or FKS3. Furthermore, in contrast to what is observed in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs, and consistently are tolerant to cell wall-damaging agents. Our data indicate that C. albicans FKS2 and FKS3 can act as negative regulators of FKS1, thereby influencing echinocandin susceptibility.

Original languageEnglish (US)
Article numbere02299-17
JournalAntimicrobial agents and chemotherapy
Volume62
Issue number4
DOIs
StatePublished - Apr 2018

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Keywords

  • Candida albicans
  • Echinocandins
  • FKS genes
  • Transcriptional regulation

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