Multiple functions of Pmt1p-mediated protein O-mannosylation in the fungal pathogen Candida albicans.
Protein mannosylation by Pmt proteins initiates O-glycosylation in fungi. We have identified the PMT1 gene and analyzed the function of Pmt1p in the fungal human pathogen Candida albicans. Mutants defective in PMT1 alleles lacked Pmt in vitro enzymatic activity, showed reduced growth rates, and tended to form cellular aggregates. In addition, multiple specific deficiencies not known in Saccharomyces cerevisiae (including defective hyphal morphogenesis; supersensitivity to the antifungal agents hygromycin B, G418, clotrimazole, and calcofluor white; and reduced adherence to Caco-2 epithelial cells) were observed in pmt1 mutants. PMT1 deficiency also led to faster electrophoretic mobility of the Als1p cell wall protein and to elevated extracellular activities of chitinase. Homozygous pmt1 mutants were avirulent in a mouse model of systemic infection, while heterozygous PMT1/pmt1 strains showed reduced virulence. The results indicate that protein O-mannosylation by Pmt proteins occurs in different fungal species, where PMT1 deficiency can lead to defects in multiple cellular functions.
Timpel
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Institut für Mikrobiologie und Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany.
Strahl-Bolsinger
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S
Ziegelbauer
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K
Ernst
J F
JF
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D017931:DNA Primers; D005656:Fungal Proteins / Q000378:metabolism*; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014774:Virulence
D017931:DNA Primers; D005656:Fungal Proteins; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D008358:Mannose