Morphogenesis, adhesive properties, and antifungal resistance depend on the Pmt6 protein mannosyltransferase in the fungal pathogen Candida albicans

Protein mannosyltransferases (Pmt proteins) initiate O glycosylation of sec reted proteins in fungi. We have characterized PMT6, which encodes the seco nd Pmt protein of the fungal pathogen Candida albicans, The residues of Pmt 6p are 21 and 42% identical to those of C. albicans Pmt1p and S. cerevisiae Pmt6p, respectively. Mutants lacking one or two PMT6 alleles grow normally and contain normal Pmt enzymatic activities in cell extracts but show phen otypes including a partial block of hyphal formation (dimorphism) and a sup ersensitivity to hygromycin B. The morphogenetic defect can be suppressed b y overproduction of known components of signaling pathways, including Cek1p , Cph1p, Tpk2p, and Efg1p, suggesting a specific Pmt6p target protein upstr eam of these components. Mutants lacking both PMT1 and PMT6 are viable and show pmt1 mutant phenotypes and an additional sensitivity to the iron chela tor ethylenediamine-di(o-hydroxyphenylacetic acid). The lack of Pmt6p signi ficantly reduces adherence to endothelial cells and overall virulence in a mouse model of systemic infection. The results suggest that Pmt6p regulates a more narrow subclass of proteins in C. albicans than Pmt1p, including se creted proteins responsible for morphogenesis and antifungal sensitivities.