title: Morphogenesis, adhesive properties, and antifungal resistance depend on the Pmt6 protein mannosyltransferase in the fungal pathogen candida albicans.
abstract: Protein mannosyltransferases (Pmt proteins) initiate O glycosylation of secreted proteins in fungi. We have characterized PMT6, which encodes the second Pmt protein of the fungal pathogen Candida albicans. The residues of Pmt6p 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 phenotypes including a partial block of hyphal formation (dimorphism) and a supersensitivity to hygromycin B. The morphogenetic defect can be suppressed by overproduction of known components of signaling pathways, including Cek1p, Cph1p, Tpk2p, and Efg1p, suggesting a specific Pmt6p target protein upstream of these components. Mutants lacking both PMT1 and PMT6 are viable and show pmt1 mutant phenotypes and an additional sensitivity to the iron chelator ethylenediamine-di(o-hydroxyphenylacetic acid). The lack of Pmt6p significantly 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 secreted proteins responsible for morphogenesis and antifungal sensitivities.
authors.affiliation: Institut für Mikrobiologie, Biologisch-Medizinisches Forschungszentrum, D-40225 Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Timpel
authors.forename: S
authors.initials: S
authors.lastname: Zink
authors.forename: S
authors.initials: S
authors.lastname: Strahl-Bolsinger
authors.forename: K
authors.initials: K
authors.lastname: Schröppel
authors.forename: J
authors.initials: J
authors.lastname: Ernst
mesh_terms: D000483:Alleles; D000818:Animals; D000935:Antifungal Agents; D002176:Candida albicans / Q000166:cytology / Q000472:pathogenicity* / Q000502:physiology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D005800:Genes, Fungal; D008364:Mannosyltransferases / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D011499:Protein Processing, Post-Translational; D017422:Sequence Analysis, DNA; D013489:Suppression, Genetic
chemical_list: D000935:Antifungal Agents; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase