Horizontal Gene Transfer as a Direct Cause of Antibiotic Resistance in Bacterial Pathogens

Abstract

Horizontal Gene Transfer (HGT) is an important mechanism for the rapid spread of antibiotic resistance determinants among bacterial pathogens. Resulting MDR strains have evolved, causing a severe threat to human health. In this review, a comprehensive compilation and discussion on the documented mechanisms underpinning HGT-transformation, transduction, and conjugation processes, play crucial roles in the transfer of antibiotic-resistance genes is presented. Key examples of resistant pathogens, such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, are drawn upon to illustrate how HGT has contributed to resistance against critical antibiotics, including beta-lactams and fluoroquinolones. I examine the HGT 'hotspots' that include the human gut microbiome, clinical environments, and external reservoirs, like wastewater plants and agricultural sites, where the exchange of ARGs prevails. It also denotes some resistance genes including BLA (beta-lactam resistance), mecA (MRSA), and NDM-1 (Enterobacteriaceae), which have broad-spectrum beta-lactam resistance. These genes carry mobile genetic elements that quicken the pace of their spread.

This review points to the very pressing need for the development of effective intervention strategies as antibiotic-resistant infections continue to rise. Some of the novel strategies that may be considered for ARG transfer disruption, including emerging approaches such as phage therapy, CRISPR-Cas systems, and anti-plasmid compounds, appear promising. This review, however, will attempt to raise awareness about the current understanding of the mechanisms of HGT, hotspots, and strategies of intervention to present a clearer picture of the problem faced in combating antibiotic resistance and signal the urgent need for globally coordinated efforts and innovative solutions.