Attenuation of Virulence and Changes in Morphology in Candida albicans by Disruption of the N -Acetylglucosamine Catabolic Pathway

Abstract

ABSTRACT A Candida albicans mutant with mutations in the N -acetylglucosamine (GlcNAc) catabolic pathway gene cluster, including the GlcNAc-6-phosphate deacetylase ( DAC1 ), glucosamine-6-phosphate deaminase ( NAG1 ), and GlcNAc kinase ( HXK1 ) genes, was not able to grow on amino sugars, exhibited highly attenuated virulence in a murine systemic candidiasis model, and was less adherent to human buccal epithelial cells in vitro. No germ tubes were formed by the mutant after induction with GlcNAc, but the mutant exhibited hyperfilamentation under stress-induced filamentation conditions. In addition, the GlcNAc catabolic pathway played a vital role in determining the colony phenotype. Our results imply that this pathway is very important because of its diverse links with pathways involved in virulence and morphogenesis of the organism.