Abstract
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.
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