Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides

• Verfasst von: Swidergall, Marc [VerfasserIn]
• Verfasst von: Ernst, Andreas M. [VerfasserIn]
• Verfasst von: Ernst, Joachim F. [VerfasserIn]
• Titel: Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides
• Verf.angabe: Marc Swidergall, Andreas M. Ernst, and Joachim F. Ernst
• E-Jahr: 2013
• Jahr: 3 June 2013
• Umfang: 6 S.
• Fussnoten: Gesehen am 27.01.2022
• Titel Quelle: Enthalten in: Antimicrobial agents and chemotherapy
• Ort Quelle: Washington, DC : Soc., 1972
• Jahr Quelle: 2013
• Band/Heft Quelle: 57(2013), 8, Seite 3917-3922
• ISSN Quelle: 1098-6596
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1787313581

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.