PBP occupancy and efflux of β-lactams in clinical isolates of Neisseria gonorrhoeae

Neisseria gonorrhoeae is showing increasing antibiotic resistance and is a significant challenge to treat. This study looked at the connection between the genetic variability of the main β-lactam target (penicillin binding protein 2; PBP2), target accessibility, and susceptibility to last-line antimicrobial class as well as potential new candidates. Genetic analysis found various factors contributing to β-lactam resistance affecting drug targets, entry and efflux. Specific substitutions in PBP2 were confirmed as the key determinant of cephalosporin resistance with notable impacts on drug sensitivity. Ertapenem and piperacillin emerged as potential therapies against resistant strains along with combination therapies involving tazobactam or efflux inhibitors. The findings provide insights for developing new antimicrobial agents against emerging resistant strains while further research is needed for better therapeutic interventions for these infections.

奈瑟氏淋球菌正呈现出日益增长的抗生素耐药性，成为治疗上的重大挑战。本研究探讨了主要β-内酰胺靶点（青霉素结合蛋白2；PBP2）的遗传变异性、靶点可及性与对最后一线抗菌药物类别敏感性之间的联系，以及潜在的新候选药物。遗传分析揭示了多种因素对β-内酰胺耐药性的影响，包括药物靶点、入侵和泵出机制。PBP2中的特定替换被确认为头孢菌素耐药性的关键决定因素，并对药物敏感性产生了显著影响。ertapenem和哌拉西林被证明是针对耐药菌株的潜在治疗药物，同时涉及他唑巴坦或泵出抑制剂联合疗法的方案也浮出水面。这些发现为开发针对新出现的耐药菌株的新型抗菌药物提供了洞见，而对于这些感染的更有效的治疗干预措施，仍需进一步研究。