Mannan Molecular Substructures Control Nanoscale Glucan Exposure in Candida

Area of Science:

• Mycology
• Immunology
• Microbial Pathogenesis

Background:

• Cell wall mannans in Candida albicans serve as a shield, masking β-(1,3)-glucan from immune recognition by Dectin-1.
• This masking is crucial for innate immune evasion by Candida species.
• Variations in glucan exposure and mannan complexity exist across different Candida species.

Purpose of the Study:

• To investigate the role of specific N-mannan features in regulating the nanoscale geometry of glucan exposure.
• To understand how N-mannan structure influences the interaction between Candida and the host immune system.

Main Methods:

• Utilized super-resolution fluorescence imaging to visualize cell wall structures.
• Employed a series of protein mannosylation mutants in Candida albicans and Candida glabrata.
• Analyzed the correlation between N-mannan structural features and glucan exposure geometry.

Main Results:

• Decreased abundance of acid labile mannan correlated with increased density of glucan exposures in C. albicans.
• Reduced α-(1,6)-mannan backbone length correlated with increased nanoscopic size of glucan exposures in C. glabrata.
• A clinical isolate of C. albicans with high glucan exposure exhibited altered N-mannan structures and enhanced glucan exposure geometry.

Conclusions:

• Acid labile mannan structure significantly influences the nanoscale features of glucan exposure on the fungal surface.
• These structural changes impact the nature of the pathogenic surface, affecting immunoreceptor engagement, aggregation, and downstream signaling.
• Understanding these mechanisms provides insights into fungal immune evasion strategies.