The Bacterial Cell Wall: New Biological Insights, Probes, and Targeting Strategies
Dr. Cullen Myers
Professor, Department of Molecular and Cellular Biology
University of Guelph
Tuesday, January 27, 2026
11 a.m.
In-person: C2-361
Abstract: Most bacteria are encapsulated by a cell wall composed of peptidoglycan (PG) that is essential for viability. It provides mechanical strength to withstand internal osmotic pressure and protects the cell from environmental stress. Decades of intensive study have established the importance of the cell wall in maintaining cell shape, with its dynamic remodelling crucial for cell growth and division. Yet, fundamental questions remain surrounding cell wall dynamics, particularly in Gram-positive bacteria. As well, current antibacterial therapies targeting PG synthesis in Gram-negative pathogens are increasingly compromised by existing and emerging resistance mechanisms. Our research focuses on these two key areas.
In Gram-positive bacteria, the polyol phosphate glycopolymer wall teichoic acid (WTA) is covalently attached to PG and accounts for roughly half of the cell wall mass. WTAs are implicated in diverse cellular processes, including morphogenesis, antimicrobial resistance, bacterial virulence, and more recently, PG biosynthesis. However, WTA degradation pathways during vegetative growth have been largely overlooked. We have identified putative WTA-degrading enzymes of both bacterial and bacteriophage origin and are employing biochemical and genetic approaches to elucidate roles in cell wall remodelling and homeostasis, and to harness these enzymes as tools to interrogate the cell surface.
Simultaneously, we are investigating alternative strategies to disrupt PG synthesis in Gram-negative bacteria. PG-synthesizing enzymes – penicillin-binding proteins (PBPs), especially PBP3 (FtsI) – are the targets of β-lactam antibiotics, the most widely used drugs for treating bacterial infections. Resistance in Gram-negative pathogens is primarily mediated by β-lactamase enzymes, but there is growing concern over the emergence of PBP3 variants that threaten to further erode β-lactam efficacy and hinder the development of small-molecule inhibitors of this valuable antibacterial target. Using RoseTTAFold diffusion, we have designed de novo peptides predicted to bind PBP3. Preliminary experiments revealed promising antibacterial activity, motivating mode-of-action studies and future efforts to integrate these peptides into engineered delivery platforms.
Originally from the Caribbean Island of St. Lucia, Dr. Myers received his PhD in Chemistry from the University of Waterloo under the supervision of Professor John Honek. He then completed postdoctoral training with Professor Eric Brown at McMaster University, before working in antibacterial drug discovery and development of β-lactamase and cell wall synthesis inhibitors in the biotech sector (Venatorx Pharmaceuticals, Malvern, PA, USA). Dr. Myers joined the Department of Molecular and Cellular Biology at the University of Guelph as an assistant professor in the summer of 2024. His research continues to delve into the complexities of the bacterial cell wall, integrating biochemical, structural, molecular and genetic approaches to examine poorly understood aspects of cell wall synthesis and maintenance.