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Antimicrob Agents Chemother. 2013 Aug;57(8):3917-22. doi: 10.1128/AAC.00862-13. Epub 2013 Jun 3.

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

Author information

1
Department Biologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.

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.

PMID:
23733470
PMCID:
PMC3719696
DOI:
10.1128/AAC.00862-13
[Indexed for MEDLINE]
Free PMC Article

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