An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis

Antimicrob Agents Chemother. 2017 May 24;61(6):e00084-17. doi: 10.1128/AAC.00084-17. Print 2017 Jun.

Abstract

We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo.

Keywords: Candida albicans; Vps21p; azoles; resistance; tolerance; vaginal candidiasis.

MeSH terms

  • Animals
  • Antifungal Agents / therapeutic use*
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Candida albicans / growth & development
  • Candidiasis, Vulvovaginal / drug therapy*
  • Candidiasis, Vulvovaginal / microbiology
  • Disease Models, Animal
  • Drug Resistance, Fungal / genetics
  • Female
  • Fluconazole / therapeutic use*
  • Membrane Transport Proteins / biosynthesis
  • Membrane Transport Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • rab GTP-Binding Proteins / genetics

Substances

  • Antifungal Agents
  • Membrane Transport Proteins
  • Fluconazole
  • rab GTP-Binding Proteins