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

Guillherme Chaves, Steven Bates, Donna Margaret MacCallum, Frank Christopher Odds

Research output: Contribution to journalArticle

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 sod1¿mutant. In vitro, the grx2¿strain, but not the sod1¿strain, was defective in hypha formation. The grx2¿strain, but not sod1¿, 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 grx2¿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 grx2¿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 Nov 2007

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Candida albicans
Virulence
Vitamin K 3
Hyphae
Reactive Oxygen Species
Glutaredoxins
Diamide
Genes
Glutathione Reductase
Virulence Factors
Oxidants
Superoxide Dismutase
Oxidative Stress
Neutrophils
Growth

Keywords

  • candida albicans
  • virulence
  • GRX2
  • glutathione reductase

Cite this

Candida albicans GRX2, encoding a putative glutaredoxi, is required for virulence in a murine model. / Chaves, Guillherme; Bates, Steven; MacCallum, Donna Margaret; Odds, Frank Christopher.

In: Genetics and Molecular Research, Vol. 6, No. 4, 27.11.2007, p. 1051-1063.

Research output: Contribution to journalArticle

Chaves, Guillherme ; Bates, Steven ; MacCallum, Donna Margaret ; Odds, Frank Christopher. / Candida albicans GRX2, encoding a putative glutaredoxi, is required for virulence in a murine model. In: Genetics and Molecular Research. 2007 ; Vol. 6, No. 4. pp. 1051-1063.
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AB - 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 sod1¿mutant. In vitro, the grx2¿strain, but not the sod1¿strain, was defective in hypha formation. The grx2¿strain, but not sod1¿, 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 grx2¿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 grx2¿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.

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