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Updated: May 10, 2026
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides
Marc Swidergall1, Andreas M Ernst, Joachim F Ernst
1Department 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.
Insights
Candida albicans Msb2* protein fragments bind and neutralize human antimicrobial peptides (AMPs) and the antibiotic daptomycin. This interaction protects fungi and bacteria, potentially compromising antibacterial therapies during coinfections.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Candida albicans is a human fungal pathogen.
- Antimicrobial peptides (AMPs) are crucial host defense molecules.
- Fungal surface proteins can influence host-pathogen interactions.
Purpose of the Study:
- To investigate the interaction between Candida albicans Msb2* glycofragment and antimicrobial peptides (AMPs).
- To determine the role of Msb2* in protecting C. albicans and coinfecting bacteria from AMPs and antibiotics.
- To assess the therapeutic implications of Msb2*-AMP interactions.
Main Methods:
- Microscale thermophoresis was used to quantify Msb2*/LL-37 binding affinity.
- Experiments involved O-glycosylation-deficient and denatured Msb2* variants.
- Coculturing and mixed biofilm models were employed to study protection against daptomycin.
Main Results:
- Msb2* high-affinity binding (KD = 73 nM) to LL-37 was demonstrated, dependent on O-glycosylation.
- Msb2* also interacted with human defensins, protecting C. albicans.
- Msb2* inactivated daptomycin, protecting Staphylococcus aureus, Enterococcus faecalis, and Corynebacterium pseudodiphtheriticum in coinfections.
Conclusions:
- Shed Msb2* from Candida albicans binds and inactivates antimicrobial peptides and daptomycin.
- This interaction compromises antibacterial therapy during coinfections.
- Msb2* represents a potential target for improving antimicrobial efficacy.
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