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

Attenuation of Virulence and Changes in Morphology in Candida albicans by Disruption of the N-Acetylglucosamine Catabolic Pathway,10.1128/IAI.69.12.78

Attenuation of Virulence and Changes in Morphology in Candida albicans by Disruption of the N-Acetylglucosamine Catabolic Pathway   (Citations: 15)
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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 hyperfilamen- tation 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. Candida albicans, which causes life-threatening superficial and systemic candidiasis in immunocompromised hosts, can invade and colonize human mucosal surfaces rich in amino sugars (29, 44). The unique ability of the pathogenic Candida species to utilize amino sugars like N-acetylglucosamine (Glc NAc) and glucosamine (GlcN) as alternate carbon sources (37) led us to surmise that there is a correlation between such specific adaptation and the virulence of the organism. Besides inducing enzymes of the catabolic pathway, GlcNAc can also induce cellular morphogenesis in C. albicans, and dimorphism is suspected to be an important aspect of manifestation of
Journal: Infection and Immunity - INFEC IMMUNITY , vol. 69, no. 12, pp. 7898-7903, 2001
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    • ...C. albicans mutants incapable of utilizing Nag are less virulent in a murine model of systemic candidiasis compared to wild type isolates [54]...

    David A. Fitzpatricket al. Analysis of gene evolution and metabolic pathways using the Candida Ge...

    • ...FE526352 1, 7 glucosamine-6-phosphate deaminase Gene inactivation attenuates the virulence of Candida albicans in a murine model [71]...

    Nalu TA Pereset al. Transcriptional profiling reveals the expression of novel genes in res...

    • ...Subsequent studies revealed C. albicans is capable of taking up GlcNAc and using it as an energy source, whereas the nonpathogenic S. cerevisiae lacks the proteins needed to transport and catabolize GlcNAc (Kumar et al., 2000; Singh et al., 2001)...
    • ...Mutational analysis indicates that the enzymes needed to catabolize GlcNAc in C. albicans also contribute to virulence (Singh et al., 2001; Yamada-Okabe et al., 2001)...
    • ...These include the enzymes that phosphorylate (Hxk1), deacetylate (Dac1), and deamidate (Nag1) GlcNAc, leading to its conversion to fructose-6-PO4 (Kumar et al., 2000; Singh et al., 2001; Yamada-Okabe et al., 2001)...
    • ...Altogether these studies indicate that NGT1 expression is specifically regulated by GlcNAc, similar to the enzymes needed for GlcNAc catabolism in C. albicans (Kumar et al., 2000; Singh et al., 2001; Yamada-Okabe et al., 2001)...
    • ...Subsequent studies revealed that the GlcNAc catabolism genes (HXK1, DAC1, and NAG1) contribute to the virulence of C. albicans in a mouse tail-vein injection model of pathogenesis (Singh et al., 2001; Yamada-Okabe et al., 2001)...

    Francisco J. Alvarezet al. Identification of an N-Acetylglucosamine Transporter That Mediates Hyp...

    • ...Other hypha-inducing media, including medium 199 buffered with sodium bicarbonate (Sigma Chemical, St. Louis, Mo.), Lee’s (27), Spider (28), and N-acetylglucosamine in salt base (47) were prepared as described elsewhere...
    • ...The cdc42-S71P mutant had an unusual crinkly colony morphology, reminiscent of other C. albicans mutants that had a mixture of yeast and pseudohyphal cells (1, 47)...

    A. L. vandenBerget al. Cdc42p GTPase Regulates the Budded-to-Hyphal-Form Transition and Expre...

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