Overuse of antibiotics and the widespread environmental accumulation of antibiotics drive the evolution and spread of antimicrobial resistance, posing a significant global health threat by reducing the effectiveness of available treatments and increasing the risk of untreatable infections. We designed and synthesized PhoPS, a novel photocaged β-lactamase inhibitor, which incorporates the pharmacophore of sulbactam caged with a photoresponsive moiety of o-nitrobiphenyl derivative. Experimental results demonstrate its rapid photoactivation, good stability in solution, and light-activated β-lactamase inhibition in vitro. PhoPS displays synergy with a cephalosporin antibiotic cefoperazone against both susceptible and resistant strains of Escherichia coli and biofilm formation. Additionally, PhoPS treatment demonstrates the potential to suppress the development of resistance in E. coli. These findings suggest that PhoPS offers a promising approach for restoring the efficacy of existing antibiotics and mitigating the emergence of AMR.

中文翻译：

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光激活抑制剂克服抗菌素耐药性并调节抗菌活性


抗生素的过度使用和抗生素在环境中的广泛积累推动了抗菌素耐药性的演变和传播，通过降低现有治疗方法的有效性和增加无法治愈的感染风险，对全球健康构成重大威胁。我们设计并合成了 PhoPS，一种新型光笼式 β-内酰胺酶抑制剂，它结合了笼式舒巴坦的药效团和光响应性 o-硝基联苯衍生物部分。实验结果表明，其光活化快，在溶液中稳定性好，在体外β-内酰胺酶抑制作用。PhoPS 与头孢菌素类抗生素头孢哌酮对大肠杆菌的敏感和耐药菌株和生物膜形成具有协同作用。此外，PhoPS 处理显示出抑制大肠杆菌耐药性发展的潜力。这些发现表明，PhoPS 为恢复现有抗生素的疗效和减轻 AMR 的出现提供了一种有前途的方法。