Differential contribution of PBP occupancy and effluxin clinical isolates of Neisseria gonorrhoeae

Neisseria gonorrhoeae is a serious and rapidly expanding global public health concern, naturally capable of genetic transformation, has been able to survive in the presence of antibiotics within various anatomical sites of its host. Recent reports have indicated treatment failures when using ceftriaxone in combination with azithromycin, the last-line combination treatment, due to extensively drug-resistant (XDR) N. gonorrhoeae strains showing high-level resistance to azithromycin, as well as resistance to ceftriaxone, cefixime, and cefotaxime. The development of resistance to ceftriaxone and other ESCs is a complex process, involving various step-wise mechanisms consist of different mutated loci that can be transmitted through homologous recombination, in a specific sequence We recently published the first comprehensive PBP-binding IC50s dataset for two type strains. In this study, our objective was to measure the PBP occupancies of clinical strains with decreasing sensitivity to first-line cephalosporins and other chemically diverse, and potentially relevant clinically ß-lactams. We then aimed to connect these measurements with their effectiveness and tolerance towards efflux pumps.