Rep1p negatively regulating MDR1 efflux pump involved in drug resistance in Candida albicans

Fungal Genet Biol. 2009 Sep;46(9):714-20. doi: 10.1016/j.fgb.2009.06.003. Epub 2009 Jun 13.

Abstract

Overexpression of MDR1 efflux pump is a major mechanism contributing to drug resistance in Candida albicans, the most common human fungal pathogen. To elucidate the regulatory pathway of drug resistance, we have identified a negative regulator of MDR1 and named it Regulator of Efflux Pump 1 (REP1). Overexpression of REP1 in Saccharomyces cerevisiae increased susceptibility to fluconazole. Furthermore, null mutations on REP1 decreased the susceptibility to antifungal drugs in C. albicans resulting from increased expression of MDR1 mRNA. Hence, Rep1p is involved in drug resistance by negatively regulating MDR1 in C. albicans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Amino Acid Sequence
  • Antifungal Agents / pharmacology
  • Base Sequence
  • Candida albicans / drug effects
  • Candida albicans / genetics*
  • Candida albicans / metabolism*
  • Candidiasis / drug therapy
  • Candidiasis / metabolism
  • Candidiasis / microbiology*
  • Cloning, Molecular
  • Drug Resistance, Fungal / genetics*
  • Fluconazole / pharmacology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Fungal*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • RNA, Fungal / analysis
  • RNA, Fungal / biosynthesis
  • RNA, Fungal / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antifungal Agents
  • Fungal Proteins
  • RNA, Fungal
  • RNA, Messenger
  • Fluconazole