Grant: Master's Award: Canada Graduate Scholarships

A resilient and versatile bacterium, Pseudomonas aeruginosa presents a significant challenge to public health as one of the leading causes of mortality associated with hospital-acquired infections. Once an individual is infected by P. aeruginosa, this bacterium readily causes extensive tissue damage, and if left untreated, can rapidly progress toward septic shock and death. The standard treatment for P. aeruginosa infections involves the penicillin class of antibiotics. However, with the popularity of penicillin prescriptions and poor antibiotic management, resistant P. aeruginosa strains continue to emerge, conferring a two-fold increase in mortality and a 50 – 70% increase in treatment cost relative to antibiotic-susceptible strains. P. aeruginosa mainly becomes resistant to penicillins through the production of beta-lactamase proteins that directly inactivate these antibiotics. The production of beta-lactamases is activated when the P. aeruginosa protein penicillin-binding protein 4 (PBP4) binds to a penicillin. Notably, not all penicillins bind to PBP4, and hence are saved from being inactivated by a beta-lactamase. Many PBP4 variants have been documented in clinical samples, but the impact of these variations on beta-lactamase production is not known. Thus, my research aims to explore how these uncharacterized, clinical PBP4 variations impact the interactions of PBP4 with different penicillins. As PBP4 also controls the production of other proteins that contribute to damaging P. aeruginosa infections, we further aim to understand if these PBP4 variations lead to worse infections when penicillins are prescribed. Overall, my research will provide evidence to help optimize antibiotic regimens and improve outcomes in patients infected with P. aeruginosa.