Reclaiming the Microbial Battlefield: Adjuvant Strategies to Overcome Antibiotic Resistance

The escalation of antibiotic resistance constitutes a significant global health crisis, urgently demanding innovative strategies to restore and amplify the effectiveness of our existing antimicrobial arsenal. This review systematically explores the diverse landscape of antibiotic adjuvants, beginning with an elucidation of their classifications and profound mechanisms of action. We meticulously detail various categories of these agents, encompassing both synthetic compounds and naturally derived molecules, highlighting their crucial functions in potentiating antibiotic activity through mechanisms such as enhancing bacterial cell permeability, modulating the expression of resistance-conferring genes and optimizing drug–target interactions. Furthermore, we critically assess current screening methodologies, particularly the advancements in high-throughput approaches, and their implications for the identification and validation of novel adjuvant candidates. The review underscores the potential of antibiotic adjuvants as a promising frontier in our global endeavor to overcome bacterial resistance and ensure the sustained utility of antimicrobial medicine.