title: Alcohol dehydrogenase I expression correlates with CDR1, CDR2 and FLU1 expression in Candida albicans from patients with vulvovaginal candidiasis.
abstract: BACKGROUND
  The most critical mechanism governing drug resistance in Candida albicans (C. albicans) involves efflux pumps, the functionality of which largely depends on energy metabolism. Alcohol dehydrogenase I (ADH1) plays an important role in intracellular energy metabolism. The aim of this study was to explore the relationship between ADH1 and drug resistance in C. albicans.
  
  
  METHODS
  Twenty clinical C. albicans samples isolated from individual patients diagnosed with vulvovaginal candidiasis, and two C. albicans strains obtained from a single parental source (the fuconazole (FLC)-sensitive strain CA-1S and the FLC-resistant strain CA-16(R)) were included in our study. In accordance with the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines, we used the microdilution method to examine the FLC minimum inhibitory concentrations (MICs) and real-time reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression levels of ADH1 and the azole resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in all the isolates.
  
  
  RESULTS
  A highly significant positive correlation between the mRNA levels of ADH1 and the MICs (rs = 0.921, P = 0.000), as well as positive correlations between the mRNA level of ADH1 and those of CDR1, CDR2 and FLU1 (rs of 0.704, 0.772 and 0.779, respectively, P < 0.01), were observed in the 20 clinical C. albicans samples. The relative expression of ADH1 was upregulated 10.63- to 17.61-fold in all of the drug-resistant isolates. No correlations were found between the mRNA levels of ADH1 and those of MDR1 or ERG11 (P > 0.05). The mRNA levels of the examined drug resistance genes were higher in the CA-16(R) strain than in CA-1(S), and the mRNA levels of ADH1 in CA-16(R) were 11.64-fold higher than those in CA-1(S) (P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that high levels of ADH1 transcription are implicated in FLC resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1.
authors.affiliation: Medical College, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Lai-qiang
authors.initials: LQ
authors.lastname: Gao
authors.forename: Shui-xiu
authors.initials: SX
authors.lastname: Li
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Song
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D002176:Candida albicans / Q000187:drug effects*; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology*; D025141:Drug Resistance, Fungal / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D018528:ATP-Binding Cassette Transporters; C094693:CDR1 protein, Candida albicans; C417782:FLU1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D015725:Fluconazole; D000426:Alcohol Dehydrogenase