Antibiotic resistance mediated by bacterial enzymes constitutes an unmet clinical challenge for public health, particularly for those currently used antibiotics that are recognized as "last-resort" defense against multidrug-resistant (MDR) bacteria. Inhibitors of resistance enzymes offer an alternative strategy to counter this threat. The combination of inhibitors and antibiotics could effectively prolong the lifespan of clinically relevant antibiotics and minimize the impact and emergence of resistance. In this review, we first provide a brief overview of antibiotic resistance mechanism by bacterial secreted enzymes. Furthermore, we summarize the potential inhibitors that sabotage these resistance pathways and restore the bactericidal activity of inactive antibiotics. Finally, the faced challenges and an outlook for the development of more effective and safer resistance enzyme inhibitors are discussed.
Keywords: antibiotic resistance; bacterial enzymes; molecules; therapeutic potential.