Up-regulation of ERG11 gene among fluconazole-resistant Candida albicans generated in vitro: is there any clinical implication?
A well-characterized matched pair of fluconazole (FLU)-susceptible and FLU-resistant isolates, in addition to a clinical resistant isolate, was analyzed. It was found a differential expression of genes: the resistant strains experimentally induced after fluconazole exposure in vitro were associated mainly with up-regulation of ERG11 gene and a clear trailing growth in broth microdilution tests, whereas the isolate with clinically acquired resistance expressed constitutively high level of CDR gene and fluconazole MIC >64 mg mL(-1) within 24 h of incubation. The phenotype of resistant cells generated in vitro was reversible, implying that an induced transcriptional up-regulation of ERG genes would be one adaptive mechanism allowing the cells to grow in the presence of azole drugs. These drugs could have a potential role in modulating genes whose up-regulation would allow cells to remain in the hosts, providing a source for further development of resistance.
Ribeiro
Mariceli Araujo
MA
Department of Pathology, Biomedical Center, Universidade Federal do Espirito Santo, Vitória ES 29.040-093, Brazil. mariceliaraujo@yahoo.com
Paula
Claudete Rodrigues
CR
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D002177:Candidiasis / Q000382:microbiology; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000378:metabolism; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests; D015854:Up-Regulation
D000935:Antifungal Agents; D005656:Fungal Proteins; D015725:Fluconazole; D004875:Ergosterol