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Cph1p negatively regulates MDR1 involved in drug resistance in Candida albicans

Hsiu-Jung Lo1, Kuo-Yun Tseng2, Yeong-Yi Kao3

  • 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; School of Dentistry, China Medical University, Taichung, Taiwan.

International Journal of Antimicrobial Agents
|March 25, 2015
PubMed

Insights

Candida albicans transcription factors Efg1p and Cph1p have opposing roles in antifungal drug resistance. Cph1p enhances susceptibility to fluconazole, while Efg1p confers resistance.

Area of Science:

  • Mycology
  • Molecular Biology
  • Antifungal Drug Resistance

Background:

  • The transcription factor Efg1p in Candida albicans is implicated in virulence and negatively regulates ERG3, affecting drug resistance.
  • Cph1p, another transcription factor, has been studied in conjunction with Efg1p regarding filamentous growth and virulence.

Purpose of the Study:

  • To investigate the distinct roles of Cph1p and Efg1p in Candida albicans drug resistance.
  • To determine the effect of CPH1 overexpression and mutation on susceptibility to antifungal agents.

Main Methods:

  • Gene manipulation (overexpression and null mutation) of CPH1 in Saccharomyces cerevisiae and Candida albicans.
  • Assessment of antifungal susceptibility to fluconazole, voriconazole, and amphotericin B.
  • Gene expression analysis, including MDR1.

Main Results:

  • Overexpression of CPH1 in Saccharomyces cerevisiae led to increased susceptibility to fluconazole.
  • In Candida albicans, a null mutation of CPH1 resulted in increased MDR1 expression.
  • The cph1 null mutant exhibited decreased susceptibility to fluconazole and voriconazole, but not amphotericin B.

Conclusions:

  • Efg1p and Cph1p exhibit opposing effects on drug resistance in Candida albicans, despite potentially similar roles in virulence.
  • Cph1p appears to play a role in increasing susceptibility to certain antifungal drugs, contrasting with Efg1p's role in resistance.
Keywords:
Candida albicansDrug resistanceEfflux pumpRegulationVirulence factor

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