Candida albicans GRX2, encoding a putative glutaredoxin, is required for virulence in a murine model

G. M. Chaves, S. Bates, D. M. MacCallum, F. C. Odds*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Resistance of Candida albicans to reactive oxygen species is thought to enhance its virulence in mammalian hosts. Genes such as SOD1, which encodes the anti-oxidant, superoxide dismutase, are known virulence factors. We disrupted the gene GRX2, which encodes a putative glutathione reductase (glutaredoxin) in C. albicans, and we compared the mutant with an sod1Δ mutant. In vitro, the grx2Δ strain, but not the sod1Δ strain, was defective in hypha formation. The grx2Δ strain, but not sod1Δ, was significantly more susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, both mutants were susceptible to 1 mM menadione, but grx2Δ null alone was resistant to diamide. Both mutants were attenuated in a murine intravenous challenge model, and a GRX2 reintegrant regained partial virulence. Emphasis on the putative function of products of genes such as SOD1 and GRX2 in resistance to oxidative stress may oversimplify their functions in the virulence process, since the grx2Δ strain also gave defective hypha formation. Both mutants were sensitive to menadione and were slow to form germ tubes, though growth rates matched controls once the lag phase was passed.

Original languageEnglish
Pages (from-to)1051-1063
Number of pages13
JournalGenetics and Molecular Research
Volume6
Issue number4
Publication statusPublished - 27 Dec 2007

Keywords

  • Candida albicans
  • Glutathione reductase
  • GRX2
  • Virulence

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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