title: A multifunctional mannosyltransferase family in Candida albicans determines cell wall mannan structure and host-fungus interactions.
abstract: The cell wall proteins of fungi are modified by N- and O-linked mannosylation and phosphomannosylation, resulting in changes to the physical and immunological properties of the cell. Glycosylation of cell wall proteins involves the activities of families of endoplasmic reticulum and Golgi-located glycosyl transferases whose activities are difficult to infer through bioinformatics. The Candida albicans MNT1/KRE2 mannosyl transferase family is represented by five members. We showed previously that Mnt1 and Mnt2 are involved in O-linked mannosylation and are required for virulence. Here, the role of C. albicans MNT3, MNT4, and MNT5 was determined by generating single and multiple MnTDelta null mutants and by functional complementation experiments in Saccharomyces cerevisiae. CaMnt3, CaMnt4, and CaMnt5 did not participate in O-linked mannosylation, but CaMnt3 and CaMnt5 had redundant activities in phosphomannosylation and were responsible for attachment of approximately half of the phosphomannan attached to N-linked mannans. CaMnt4 and CaMnt5 participated in N-mannan branching. Deletion of CaMNT3, CaMNT4, and CaMNT5 affected the growth rate and virulence of C. albicans, affected the recognition of the yeast by human monocytes and cytokine stimulation, and led to increased cell wall chitin content and exposure of beta-glucan at the cell wall surface. Therefore, the MNT1/KRE2 gene family participates in three types of protein mannosylation in C. albicans, and these modifications play vital roles in fungal cell wall structure and cell surface recognition by the innate immune system.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
authors.forename: Héctor M
authors.initials: HM
authors.lastname: Mora-Montes
authors.forename: Steven
authors.initials: S
authors.lastname: Bates
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Luis
authors.initials: L
authors.lastname: Castillo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Brand
authors.forename: Ed T
authors.initials: ET
authors.lastname: Buurman
authors.forename: Diana F
authors.initials: DF
authors.lastname: Díaz-Jiménez
authors.forename: Bart
authors.initials: B
authors.lastname: Jan Kullberg
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
mesh_terms: D002176:Candida albicans / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006031:Glycosylation; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008351:Mannans / Q000737:chemistry* / Q000378:metabolism*; D008364:Mannosyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D009154:Mutation; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D008351:Mannans; D008364:Mannosyltransferases