The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance

Rev Iberoam Micol. 2013 Jul-Sep;30(3):209-12. doi: 10.1016/j.riam.2013.01.001. Epub 2013 Feb 9.

Abstract

Background: For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species.

Aims: In this study we investigated missense mutations in ERG11 genes of Candida albicans, Candida glabrata and Candida tropicalis isolates previously evaluated by susceptibility testing to fluconazole.

Methods: Screening for these mutations was performed on 19 Candida clinical isolates (eight C. albicans, five C. glabrata and six C. tropicalis) resistant and susceptible to fluconazole. The ERG11 gene was amplified by PCR with specific primers for each Candida species and analyzed by automated sequencing.

Results: We identified 14 different missense mutations, five of which had not been described previously. Among them, a new mutation L321F was identified in a fluconazole resistant C. albicans isolate and it was analyzed by a theoretical three-dimensional structure of the ERG11p.

Conclusion: The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance.

Keywords: Candida; Drug resistance; ERG11 gene; Fluconazol; Fluconazole; Gen ERG11; Mutación; Mutation; Resistencia farmacológica.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Candida albicans / drug effects
  • Candida albicans / genetics*
  • Candida glabrata / genetics
  • Candida tropicalis / genetics
  • Candidemia / microbiology
  • Candidiasis, Oral / microbiology
  • DNA Mutational Analysis
  • DNA, Fungal / genetics
  • Drug Resistance, Fungal / genetics*
  • Fluconazole / pharmacology*
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics*
  • Fungal Proteins / physiology
  • Genes, Fungal*
  • Humans
  • Models, Molecular
  • Mutation, Missense*
  • Point Mutation*
  • Protein Conformation
  • Sterol 14-Demethylase / chemistry
  • Sterol 14-Demethylase / genetics*
  • Sterol 14-Demethylase / physiology

Substances

  • DNA, Fungal
  • Fungal Proteins
  • Fluconazole
  • Sterol 14-Demethylase