Mechanisms of antimicrobial drug resistance

Abstract

Antimicrobial resistance occurs through enzyme-driven drug breakdown, bacterial protein modifications, and alterations in antibiotic permeability, and can be transmitted through plasmids or ingrained within the bacterial chromosome. The primary mechanism responsible for resistance to cephalosporins and penicillin is the enzymatic hydrolysis of these antibiotics by the bacterial enzyme β-lactamase. The presence of chromosomal β- lactamase can be influenced by exposure to β-lactam drugs, leading to either induced expression or sustained inhibition. Strategies to counteract resistance to β-lactam antibiotics involve two main approaches: first, the development of novel antibiotics that are resistant to β-lactamase degradation; and second, the concurrent use of β-lactamase inhibitors alongside β-lactam drugs. Methicillin resistance, which remains unaffected by gram-positive β-lactamase, arises due to modifications in penicillin-binding protein. The main mechanisms of resistance for other classes of antibiotics, encompassing trimethoprim, sulphonamides, aminoglycosides, chloramphenicol and quinolones, involve two key processes: the creation of enzymes that modify the antibiotics, and the development of bacterial targets that are resistant to the effects of these antibiotics. For several antibiotic families, including quinolones, aminoglycosides, β-lactams and chloramphenicol, decreased antibiotic penetration acts as an additional resistance mechanism.