812 Talk: The role of C. albicans cell wall in mediating interkingdom interactions during gastrointestinal colonization

Seminar Details
Friday, April 9, 2021 - 12:00pm to 1:00pm


Faith Anderson, Ph.D. Candidate
O'Meara Lab, Department of Microbiology & Immunology, University of Michigan


Zoom Meeting: 


Meeting ID: 944 6835 3155
Passcode: 340574

Candida albicans is a commensal mucosal colonizer and a leading cause of invasive fungal infections. The multi-layered cell wall of C. albicans plays a vital role in shaping the complex interactions between C. albicans and immune cells, as well mediating interactions between C. albicans and other microbes that colonize mucosal surfaces. Macrophages respond to C. albicans by recognizing B-1,3-glucan on the fungal cell wall, which leads to phagocytic uptake. The outer mannan layer can be remodeled to act as a shield, restricting access of the pattern recognition receptor Dectin-1 to the B-1,3-glucan ligand. Upon phagocytosis, C. albicans escapes by triggering the inflammatory host cell death program, pyroptosis. Recent efforts to elucidate fungal triggers of pyroptosis suggest that cell wall remodeling upon phagocytosis is required for activation of the inflammasome. This links the cell wall to both the recognition and the downstream inflammatory output of macrophages.

Furthermore, mannan extracted from the cell wall of C. albicans can act as a carbon source for Bacteroides thetaiotaomicron, a prominent member of the gut microbiota. In a murine colonization model, these two microbes associate closely in the outer mucus layer of the gastrointestinal tract, indicating the potential for relevant polymicrobial interactions. I hypothesize that the cell wall of C. albicans, particularly the mannan layer, controls interactions with both immune cells and other gut microbes. Of importance, I believe these interactions have a role in determining how and whether C. albicans shifts from a commensal colonizer to a disease-causing state. For example, in patients with inflammatory bowel disease, bacterial dysbiosis may promote overgrowth of C. albicans, and a resulting overactive inflammatory immune response. Here, I will present my ongoing work in characterizing the role of the C. albicans cell wall in modulating inflammation, with a focus on the NLRP3 inflammasome. I will examine C. albicans intrinsic factors, such as the uncharacterized cell wall protein, Pga52; as well as external factors, such as the interaction between C. albicans and B. thetaiotaomicron, in regulating macrophage activation of pyroptosis.