Reduced virulence of Candida albicans mutants lacking the GNA1 gene encoding glucosamine-6-phosphate acetyltransferase

Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan 1 Author for correspondence: Toshiyuki Mio. Tel: +81 467 47 2242. Fax: +81 467 46 5320. e-mail: toshiyuki.mio{at}roche.com The yeast GNA1 gene encodes glucosamine-6-phosphate acetyltransferase which catalyses the reaction of glucosamine 6-phosphate with acetyl-CoA to form N -acetylglucosamine 6-phosphate, a fundamental precursor in UDP- N -acetylglucosamine biosynthesis. Candida albicans mutants lacking GNA1 were viable in the presence of N -acetylglucosamine. To confirm the physiological importance of C. albicans GNA1 , the virulence of a C. albicans gna1 null mutant was examined in a mouse model of candidiasis. When injected intravenously into mice, the virulence of the C. albicans gna1 null mutant was significantly attenuated. The reduced virulence appeared to be the result of rapid clearance from host tissue. These data suggest that C. albicans GNA1 is required for survival of the fungus in host animals, probably because an insufficient level of N -acetylglucosamine is available from the host tissues. Keywords: GNA1 , glucosamine-6-phosphate acetyltransferase, antifungal target, Candida albicans , virulence Abbreviations: GalNAc, N -acetylgalactosamine; GlcNAc, N -acetylglucosamine; ManNAc, N -acetylmannosamine