title: Reduced virulence of Candida albicans mutants lacking the GNA1 gene encoding glucosamine-6-phosphate acetyltransferase.
abstract: 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 gna1Delta null mutant was examined in a mouse model of candidiasis. When injected intravenously into mice, the virulence of the C. albicans gna1Delta 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.
authors.affiliation: Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan1.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mio
authors.affiliation: Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan1.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kokado
authors.affiliation: Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan1.
authors.forename: Mikio
authors.initials: M
authors.lastname: Arisawa
authors.affiliation: Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan1.
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency*; D000818:Animals; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005800:Genes, Fungal; D051081:Glucosamine 6-Phosphate N-Acetyltransferase; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D009154:Mutation; D013997:Time Factors; D014774:Virulence
chemical_list: D000123:Acetyltransferases; D051081:Glucosamine 6-Phosphate N-Acetyltransferase; C494972:Gnpnat1 protein, mouse