COMBATTING ANTIMICROBIAL RESISTANCE: ADVANCES IN DRUG DESIGN AND NOVEL TREATMENT STRATEGIES

Uppu Manasa*, P. Sailaja and Y. Prapurnachandra

ABSTRACT

Antimicrobial resistance (AMR) has emerged as a critical global health challenge, significantly contributing to increased morbidity and mortality. The primary mechanisms of resistance include restricted drug uptake, modification of drug targets, enzymatic inactivation, and active efflux of antimicrobial agents. These resistance strategies can be either intrinsic to microorganisms or acquired through horizontal gene transfer. Among these, efflux transporters play a vital role in bacterial defense, actively expelling antibiotics and other toxic compounds from the cytoplasm or surrounding membranes into the external environment. Based on their sequence similarities, substrate specificity, and energy sources, bacterial multidrug efflux pumps are classified into seven major families: ATP-binding cassette (ABC), resistance-nodulation-division (RND), major facilitator superfamily (MFS), small multidrug resistance (SMR), multidrug and toxic compound extrusion (MATE), proteobacterial antimicrobial compound efflux (PACE), and AbgT transporters. These transporters vary in function, with some exhibiting specificity for a single compound while others accommodate a wide range of structurally diverse molecules. Gram-negative bacteria, which comprise the majority of pathogens on the World Health Organization (WHO) priority list, exhibit higher resistance levels than Gram-positive bacteria due to their unique cell wall structure. This makes infections caused by Gram-negative bacteria more difficult to treat, leading to severe health consequences. The continuous evolution and spread of AMR pose a serious threat, rendering several infectious diseases increasingly difficult or even impossible to treat. Therefore, understanding the molecular mechanisms underlying resistance and developing innovative therapeutic approaches are crucial to combating AMR and reducing its global impact.

Keywords: Antimicrobial resistance (AMR), Multidrug efflux pumps, Gram-negative bacteria, Drug resistance mechanisms, Novel antimicrobial strategies.