Exploring the diversity of mycobacteria cell surface modifying enzymes

Patrick Moynihan (University of Western Ontario, Canada)

12:15 - 12:35 Tuesday 14 April Morning

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Abstract

The mycobacterial cell envelope is a complex and dynamic structure that plays a critical role in pathogenesis, immune evasion, and antibiotic resistance. Despite extensive characterization of its lipid and carbohydrate components, the enzymatic processes governing its remodeling remain incompletely understood. I will discuss the discovery of new enzymes that modify the mycobacterial cell surface through targeted alterations of arabinomannan and related glycoconjugates. Using a combination of biochemical assays, genetic knockouts, and cell surface profiling, we demonstrate that these enzymes catalyze specific modifications that influence cell wall architecture and permeability. Functional studies reveal that loss or overexpression of these enzymes significantly alters mycobacterial growth dynamics, colony morphology, and susceptibility to host-derived stressors. Some enzymes appear to regulate the presentation of immunomodulatory glycans, suggesting a role in host-pathogen interactions. Our findings expand the repertoire of known cell envelope-modifying enzymes and highlight a new layer of regulation in mycobacterial biology. These insights not only deepen our understanding of mycobacterial physiology but also open avenues for therapeutic intervention targeting cell surface remodeling pathways.

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