Biochemistry Seminar: Karl Glen – PhD Candidate
Pseudomonas aeruginosa is an opportunistic pathogen capable of causing severe infections in the immunocompromised and individuals with chronic lung disease.
The antibiotic meropenem is a key player in the treatment of P. aeruginosa, inhibiting the essential penicillin-binding protein 3 (PBP3). Variants of the gene ftsI that encode PBP3 are thought to be associated with meropenem resistance in P. aeruginosa. Resistance may also arise by acquisition of β-lactamase enzymes that degrade meropenem.
This research aimed to understand the effects of ftsI variants and the acquisition of β-lactamases on meropenem resistance. Expressing ftsI variants using an inducible expression vector reduced the effectiveness of meropenem for P. aeruginosa. Five ftsI variants were also engineered into the genome of P. aeruginosa replacing the wild-type ftsI gene. These variants increased resistance to meropenem and other β-lactam antibiotics. They also reduced growth rate and altered cell morphology. Α variety of β-lactamases were expressed from an inducible vector and screened for their contribution towards β-lactam resistance. The β-lactamases all had different resistance profiles towards β-lactam antibiotics.
The results from this research will contribute to our understanding of the development of meropenem resistance in an important pathogen.
Zoom link: https://otago.zoom.us/j/97756704741