Inhibiting horizontal gene transfer to contain antimicrobial resistance: conjugation and plasmid maintenance as druggable targets

INTRODUCTION: Antimicrobial resistance (AMR) is propelled by horizontal gene transfer (HGT), with conjugative plasmids enabling rapid, cross-species spread and stable carriage of resistance. Interventions that reduce plasmid transmission or persistence can complement bactericidal therapies and infection-control programs. AREAS COVERED: literature. We cover biological antagonists (exclusion, fertility inhibition, and host defenses), chemical and metabolic inhibitors, and genetic strategies that repress transfer functions or selectively eliminate resistance elements. EXPERT OPINION: HGT inhibition is moving from proof-of-concept to actionable containment, but progress depends on mechanism-confirmed leads, standardized transfer metrics, plasmid confirmation, and safety evaluation in complex microbiomes and environments. Near-term impact is most likely as an adjunct to stewardship and infection prevention, aiming to reduce new acquisition and shorten carriage of high-risk resistance plasmids.