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

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

Aberdeen Fungal Group, School of Medical Sciences,
Institute of Medical Sciences, Aberdeen, UK
The present address of G.M. Chaves is Disciplina de Infectologia,
Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
Corresponding author: F.C. Odds
E-mail: f.odds@abdn.ac.uk

Genet. Mol. Res. 6 (4): 1051-1063 (2007)
Received May 10, 2007
Accepted October 11, 2007
Published November 27, 2007

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 sod1Δmutant. In vitro, the grx2Δstrain, but not the sod1Δ strain, was defective in hypha formation. The grx2Δstrain, 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 grx2Δnull 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 grx2Δstrain 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.

Key words: Candida albicans, Virulence, GRX2, Glutathione reductase