Mucin O-glycans are natural inhibitors of Candida albicans pathogenicity

Area of Science:

• Microbiology
• Glycobiology
• Pathogen Host Interactions

Background:

• Mucins form the mucus barrier, inhibiting Candida albicans filamentation, a key virulence factor.
• The specific molecular components of mucins responsible for this inhibition are not well understood.
• Understanding these motifs could lead to novel therapeutic strategies against fungal pathogens.

Purpose of the Study:

• To identify the molecular motifs within mucins that inhibit Candida albicans filamentation.
• To evaluate the therapeutic potential of these identified motifs in managing fungal infections.

Main Methods:

• Isolation and cataloging of over 100 mucin O-glycans from three mucosal surfaces.
• Assessment of O-glycan effects on Candida albicans filamentation and related virulence phenotypes (adhesion, biofilm formation, inter-kingdom competition).
• Synthesis and testing of specific O-glycan structures for their inhibitory capacity.

Main Results:

• Mucin O-glycans were identified as potent virulence-attenuating molecules.
• Isolated O-glycans suppressed Candida albicans filamentation, surface adhesion, biofilm formation, and competition with Pseudomonas aeruginosa.
• Three specific O-glycan structures (core 1, core 1+fucose, and core 2+galactose) demonstrated significant inhibitory activity.

Conclusions:

• Mucin O-glycans are key host molecules that suppress Candida albicans virulence.
• These O-glycans represent a promising, untapped therapeutic target for controlling fungal pathogens.
• Targeting mucin O-glycans could offer a novel approach to managing Candida albicans infections.