Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes

The global spread of antibiotic resistance has posed a serious threat to public healthcare and undermined decades of progress made in the fight against bacterial infections. It has been demonstrated that the lack of novel effective antibiotics and rapid spread of antibiotic resistance genes via horizontal transfer in the ecosystem are mainly responsible for this crisis. Notably, plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) is recognized as the most dominant dissemination pathway of ARGs in humans, animals and environmental settings. Antibiotic selective pressure has always been regarded as one of the crucial contributors to promoting the dissemination of antibiotic resistance through horizontal gene transfer (HGT). However, the roles of exogenous compounds and particularly non-antibiotic drugs in the spread of ARGs are still underappreciated. In this review, we first summarize the major pathways of HGT in bacteria, including conjugation, transformation, transduction and vesiduction. Subsequently, an overview of these compounds capable of promoting the HGT is presented, which guides to the formulation of more reasonable dosing regimens and drug residue standards in clinical practice. By contrast, these compounds that display an inhibition effect on HGT are also highlighted, which provides a unique strategy to minimize the spread of ARGs. Lastly, we discuss the implementations and challenges in bringing these HGT inhibitors into clinical trials.