title: Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides.
abstract: The human fungal pathogen Candida albicans releases a large glycofragment of the Msb2 surface protein (Msb2*) into the growth environment, which protects against the action of human antimicrobial peptides (AMPs) LL-37 and histatin-5. Quantitation of Msb2*/LL-37 interactions by microscale thermophoresis revealed high-affinity binding (dissociation constant [KD] = 73 nM), which was lost or greatly diminished by lack of O-glycosylation or by Msb2* denaturation. Msb2* also interacted with human α- and β-defensins and protected C. albicans against these AMPs. In addition, the lipopeptide antibiotic daptomycin was bound and inactivated by Msb2*, which prevented the killing of bacterial pathogens Staphylococcus aureus, Enterococcus faecalis, and Corynebacterium pseudodiphtheriticum. In coculturings or mixed biofilms of S. aureus with C. albicans wild-type but not msb2 mutant strains, the protective effects of Msb2* on the bactericidal action of daptomycin were demonstrated. These results suggest that tight binding of shed Msb2* to AMPs that occurs during bacterial coinfections with C. albicans compromises antibacterial therapy by inactivating a relevant reserve antibiotic.
authors.affiliation: Department Biologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Swidergall
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Ernst
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Ernst
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018920:Coculture Techniques; D017576:Daptomycin / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects; D005656:Fungal Proteins / Q000378:metabolism*; D006031:Glycosylation; D054808:Histatins / Q000494:pharmacology; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D009077:Mucins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D023084:alpha-Defensins / Q000378:metabolism / Q000494:pharmacology; D023083:beta-Defensins / Q000494:pharmacology; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C406407:DEFB1 protein, human; D005656:Fungal Proteins; C068075:HTN3 protein, human; D054808:Histatins; D009077:Mucins; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1; D017576:Daptomycin; D054804:Cathelicidins