Candida albicans GRX2, encoding a putative glutaredoxin, is required for virulence in a murine model.
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 sod1Deltamutant. In vitro, the grx2Deltastrain, but not the sod1Delta strain, was defective in hypha formation. The grx2Deltastrain, but not sod1Delta, 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 grx2Deltanull 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 grx2Deltastrain 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.
Chaves
G M
GM
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, Aberdeen, UK.
Bates
S
S
Maccallum
D M
DM
Odds
F C
FC
D000818:Animals; D001483:Base Sequence; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D002177:Candidiasis / Q000209:etiology / Q000382:microbiology; D015169:Colony Count, Microbial; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D005800:Genes, Fungal; D054477:Glutaredoxins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology; D018384:Oxidative Stress; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D014774:Virulence / Q000235:genetics / Q000502:physiology; D024483:Vitamin K 3 / Q000494:pharmacology; D000099156:Superoxide Dismutase 2
D017931:DNA Primers; D004271:DNA, Fungal; D054477:Glutaredoxins; D013482:Superoxide Dismutase; D024483:Vitamin K 3; D000099156:Superoxide Dismutase 2