Two membrane proteins located in the Nag regulon of Candida albicans confer multidrug resistance

Biochem Biophys Res Commun. 2003 Feb 21;301(4):1099-108. doi: 10.1016/s0006-291x(03)00094-9.

Abstract

Pathogenic fungus Candida albicans can efficiently utilize the aminosugar N-acetylglucosamine (GlcNAc) as energy source. Since the mucosal membrane, the site of infection is rich in amino sugars, this specific adaptation is important for the establishment of infection. The genes encoding for the enzymes of the GlcNAc catabolic pathway, GlcNAc kinase (HXK1), GlcNAc-6-phosphate deacetylase (DAC1), and glucosamine-6-phosphate deaminase (NAG1), are present in a cluster, the Nag regulon, which is associated with virulence. In this study, we have characterized two genes, TMP1 and TMP2, present within the Nag regulon, upstream to DAC1. They encode two membrane associated sugar transporters of the major facilitator superfamily (MFS). The null mutant of TMP1 and TMP2 is able to grow in GlcNAc, implying that they are not involved in GlcNAc transport. However, it shows increased susceptibility to a number of unrelated antifungal compounds such as cycloheximide, 4-nitroquinoline-N-oxide, and 1-10 phenanthroline. Northern blot analysis revealed that TMP1 and TMP2 are upregulated in response to these drugs, suggesting that they function as multiple drug efflux pumps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism
  • Amino Acid Sequence
  • Biological Transport, Active
  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Candida albicans / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Drug Resistance, Multiple, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genes, Fungal
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Regulon
  • Sequence Homology, Amino Acid
  • Transcriptional Activation

Substances

  • Carrier Proteins
  • Fungal Proteins
  • Membrane Proteins
  • Acetylglucosamine