Seminar - Stress Testing the Bacterial Cell Wall

Sponsored by UBC Department of Microbiology & Immunology
 

Abstract: The bacterial cell wall is the essential stress-bearing layer responsible for cellular morphogenesis and integrity. Its primary component, peptidoglycan, is a dynamic heteropolymer that undergoes continual biosynthesis and remodelling during growth and division. This process is highly coordinated, and its disruption through the action of cell wall-active antibiotics results in bacterial death. Many resistance mechanisms are known to overcome cell wall-active antibiotics, including enzymatic inactivation or target modification. However, intrinsic antibiotic resistance, or tolerance, caused by genetic or biochemical adaptations is cryptic and poorly understood. Cryptic processes that confer antibiotic tolerance can be uncovered by stress testing the cell wall in genome-wide gene deletion libraries. An approach leveraging type V glycopeptide antibiotics as chemical probes will be presented to identify the mechanisms underpinning how bacteria withstand certain antibiotics. The findings of this work could guide the detection of antibiotic resistant bacteria while identifying new targets for developing antibiotic potentiators.