title: Mutations and/or Overexpressions of ERG4 and ERG11 Genes in Clinical Azoles-Resistant Isolates of Candida albicans.
abstract: OBJECTIVE
  We aimed to investigate whether mutations and/or overexpressions of ERG4 and ERG11 genes were involved in drug resistance to azoles in Candida albicans.
  
  
  METHODS
  Totally, 34 clinical isolates of C. albicans were included in this study. Antimicrobial susceptibility tests, including 5-fluorocytosine (5-FC), amphotericin B (AMB), fluconazole (FCA), itraconazole (ITR), and voriconazole (VRC), were performed by broth microdilution method. Mutations in the ERG4 and ERG11 genes sequence were detected. The messenger RNA (mRNA) levels of ERG4 and ERG11 were measured by quantitative real-time polymerase chain reaction. The correlation of the expression levels of ERG4 with ERG11 genes in susceptible isolates and resistant isolates was analyzed by Pearson's correlation analysis.
  
  
  RESULTS
  Among 34 C. albicans isolates, 52.94%, 70.59%, and 50.00% isolates were resistant to FCA, ITR, and VRC, respectively. Sequencing results revealed that only 2 silent mutations were found in ERG4 gene, while 10 amino acid substitutions, including 6 reported previously and 4 new identified, were frequently found in ERG11 gene. The mRNA levels of ERG4 and ERG11 genes were significantly elevated in resistant compared with susceptible C. albicans isolates. Furthermore, the mRNA level of ERG4 was positively correlated with ERG11 in susceptible but not resistant C. albicans isolates.
  
  
  CONCLUSIONS
  The resistance to azoles may be associated with the mutations in ERG11 but not ERG4 gene in C. albicans isolates. In addition, overexpressed ERG4 and ERG11 genes are found in resistant C. albicans isolates, and the mRNA levels of ERG4 may be irrelevant to ERG11 in resistant C. albicans isolates.
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Wenli
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Zusha
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Yaping
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Yiru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
authors.forename: Wen
authors.initials: W
authors.lastname: Cen
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology; D005437:Flucytosine / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D012333:RNA, Messenger; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System; D005437:Flucytosine; D010088:Oxidoreductases; C022673:delta 24-sterol reductase; D065819:Voriconazole
keywords: Candida albicans; ERG11; ERG4; azoles; drug resistance