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Mechanisms of fluconazole resistance in clinical isolates of Candida glabrata

YAO Dong-ting, YING Chun-mei   

  1. Clinical Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China
  • Online:2014-01-28 Published:2014-01-29

Abstract:

Objective To investigate the different expression levels of CDR1, CDR2, SNQ2, and ERG11 genes and the mutation of ERG11 gene in order to explore their roles in inducing fluconazole resistance in Candida glabrata. Methods Efflux of rhodamine 6G was performed to evaluate the effects of efflux pumps. The expression levels of CDR1, CDR2, SNQ2, and ERG11 genes were determined by real-time PCR. Meanwhile, the sequences of ERG11 were determined by PCR based DNA sequencing. Mutation of ERG11 gene was compared between fluconazole resistant and susceptible isolates. Results Efflux pumps of fluconazole resistant isolates had stronger effects than fluconazole susceptible isolates, consistently with significant upregulation of CDR1 and CDR2 (P<0.01, P<0.05). But no remarkable difference was found in SNQ2 and ERG11 expression levels (P>0.05). Four kinds of synonymous point mutation in ERG11 gene were found, which were three in both fluconazole resistant and susceptible isolates and one in susceptible isolates. Conclusion The efflux pumps play an important role in the development of fluconazole resistance in Candida glabrata. ERG11 gene mutation was found without association with the fluconazole resistance.

Key words: Candida glabrata, efflux pumps, ERG11, fluconazole