Light-Activable Inhibitor Overcomes Antimicrobial Resistance and Regulates Antibacterial Activity

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.