title: The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance.
authors: Laboratory of Medical Mycology (LIM-53)-Clinical Dermatology Division, Hospital das Clínicas da FMUSP e Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, State of São Paulo, Brazil. Electronic address: vagnercarvalho@usp.br.
authors: Vagner
authors: V
authors: Oliveira Carvalho
authors: Thelma S
authors: TS
authors: Okay
authors: Márcia S C
authors: MS
authors: Melhem
authors: Maria
authors: M
authors: Walderez Szeszs
authors: Gilda M B
authors: GM
authors: del Negro
mesh_terms: D000483:Alleles; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics*; D041221:Candida glabrata / Q000235:genetics; D041022:Candida tropicalis / Q000235:genetics; D058387:Candidemia / Q000382:microbiology; D002180:Candidiasis, Oral / Q000382:microbiology; D004252:DNA Mutational Analysis; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005800:Genes, Fungal; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D017354:Point Mutation; D011487:Protein Conformation; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D015725:Fluconazole; D058886:Sterol 14-Demethylase
keywords: Candida; Drug resistance; ERG11 gene; Fluconazol; Fluconazole; Gen ERG11; Mutación; Mutation; Resistencia farmacológica