AmpC-Induced Surge in β-Lactam Resistance in Pseudomonas aeruginosa: A Rising Danger.

Abstract

Multidrug-resistant Pseudomonas aeruginosa poses escalating threats in healthcare settings. This review highlights AmpC β-lactamase's key role in conferring β-lactam resistance. We investigate the regulatory network of ampR, ampD, and ampG genes that control AmpC expression, specifically how mutations cause enzyme overproduction. The study explores AmpC structural characteristics and mutations in conserved regions that improve catalytic performance against newer cephalosporins and carbapenems. The review covers the interaction between penicillin-binding proteins (PBPs) and AmpC β-lactamases, highlighting how PBP alteration affects enzyme production and resistance patterns. To combat resistant P. aeruginosa, we evaluate alternative therapeutic approaches, including collateral sensitivity strategies and phytochemicals as novel antimicrobials or antibiotic adjuvants. This review elucidates the complicated mechanisms that drive AmpC-mediated resistance, providing critical information that is directly applicable to healthcare practice. The findings help to develop personalized therapeutic methods, improve antimicrobial stewardship protocols, and design diagnostic tools for rapid resistance detection. By bridging molecular research to clinical practice, this study explains therapy failures and proposes new intervention techniques, such as phytochemical-enhanced combination therapies and collateral sensitivity methods. This comprehensive understanding promotes the development of precision treatment strategies, ultimately improving patient outcomes and preventing the spread of multidrug-resistant P. aeruginosa in healthcare facilities and communities.