title: O-mannosylation in Candida albicans enables development of interkingdom biofilm communities.
abstract: Candida albicans is a fungus that colonizes oral cavity surfaces, the gut, and the genital tract. Streptococcus gordonii is a ubiquitous oral bacterium that has been shown to form biofilm communities with C. albicans. Formation of dual-species S. gordonii-C. albicans biofilm communities involves interaction of the S. gordonii SspB protein with the Als3 protein on the hyphal filament surface of C. albicans. Mannoproteins comprise a major component of the C. albicans cell wall, and in this study we sought to determine if mannosylation in cell wall biogenesis of C. albicans was necessary for hyphal adhesin functions associated with interkingdom biofilm development. A C. albicans mnt1Δ mnt2Δ mutant, with deleted α-1,2-mannosyltransferase genes and thus defective in O-mannosylation, was abrogated in biofilm formation under various growth conditions and produced hyphal filaments that were not recognized by S. gordonii. Cell wall proteomes of hypha-forming mnt1Δ mnt2Δ mutant cells showed growth medium-dependent alterations, compared to findings for the wild type, in a range of protein components, including Als1, Als3, Rbt1, Scw1, and Sap9. Hyphal filaments formed by mnt1Δ mnt2Δ mutant cells, unlike wild-type hyphae, did not interact with C. albicans Als3 or Hwp1 partner cell wall proteins or with S. gordonii SspB partner adhesin, suggesting defective functionality of adhesins on the mnt1Δ mnt2Δ mutant. These observations imply that early stage O-mannosylation is critical for activation of hyphal adhesin functions required for biofilm formation, recognition by bacteria such as S. gordonii, and microbial community development. IMPORTANCE In the human mouth, microorganisms form communities known as biofilms that adhere to the surfaces present. Candida albicans is a fungus that is often found within these biofilms. We have focused on the mechanisms by which C. albicans becomes incorporated into communities containing bacteria, such as Streptococcus. We find that impairment of early stage addition of mannose sugars to C. albicans hyphal filament proteins deleteriously affects their subsequent performance in mediating formation of polymicrobial biofilms. Our analyses provide new understanding of the way that microbial communities develop, and of potential means to control C. albicans infections.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Dutton
authors.forename: Angela H
authors.initials: AH
authors.lastname: Nobbs
authors.forename: Katy
authors.initials: K
authors.lastname: Jepson
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jepson
authors.forename: M Margaret
authors.initials: MM
authors.lastname: Vickerman
authors.forename: Sami
authors.initials: S
authors.lastname: Aqeel Alawfi
authors.forename: Carol A
authors.initials: CA
authors.lastname: Munro
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lamont
authors.forename: Howard F
authors.initials: HF
authors.lastname: Jenkinson
mesh_terms: D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000378:metabolism / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D056265:Microbial Interactions; D009055:Mouth / Q000382:microbiology; D054773:Streptococcus gordonii / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C025363:mannoproteins; D008364:Mannosyltransferases
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