Mechanisms of Antimicrobial Resistance in Gram-Negative Bacteria: A Review of β-Lactamases, Efflux Pumps, and Horizontal Gene Transfer

Abstract

Antimicrobial resistance (AMR) is a major global health problem that makes many common bacterial infections harder to treat. This global problem causes longer hospital stays, higher treatment costs, and increased deaths worldwide. Gram-negative bacteria are especially important in this crisis because they can resist many antibiotics and spread easily in hospitals and communities. Although individual antimicrobial resistance mechanisms in Gram-negative bacteria are well characterized, the interactions and combined effects of multiple mechanisms, particularly their synergistic contributions to high-level resistance, remain incompletely understood. This mini narrative review examines three main resistance mechanisms in Gram-negative bacteria, namely β-lactamase enzymes, efflux pump systems, and horizontal gene transfer. A literature search was conducted in PubMed, Web of Science, Google Scholar and Scopus using the keywords “horizontal gene transfer”, “Gram-negative bacteria”, “β-lactamase,” and “efflux pump” and boolen operators “AND, OR”. Articles used were mostly publications between 2015 and 2025. The findings show that β-lactamases break down antibiotics such as penicillin and carbapenems, Efflux pumps reduce antibiotic concentration inside bacterial cells by actively pumping drugs out, and horizontal gene transfer spreads resistance genes quickly through plasmids, transposons, and integrons. These mechanisms most of the time work in synchronization in the cell, creating a stronger and more complex multilayered resistance pattern, as explained in detail in the full review article below. Overall, antimicrobial resistance in Gram-negative bacteria is driven by multiple interacting systems rather than a single mechanism, highlighting the need for integrated diagnostic, treatment, and surveillance strategies to effectively control its global impact.