ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia Patient on Posaconazole Prophylaxis

Antimicrob Agents Chemother. 2017 Jun 27;61(7):e02496-16. doi: 10.1128/AAC.02496-16. Print 2017 Jul.

Abstract

In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in Candida tropicalis.

Keywords: Candida tropicalis; ERG11 mutation; MDR1; acute leukemia; azole resistance; candidiasis; posaconazole.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use*
  • Azoles / pharmacology
  • Azoles / therapeutic use
  • Candida tropicalis / drug effects
  • Candida tropicalis / pathogenicity*
  • Drug Resistance, Fungal / genetics
  • Fluconazole / pharmacology
  • Fluconazole / therapeutic use
  • Fungal Proteins / genetics*
  • Humans
  • Microbial Sensitivity Tests
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / microbiology*
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use*

Substances

  • Antifungal Agents
  • Azoles
  • Fungal Proteins
  • Triazoles
  • posaconazole
  • Fluconazole