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

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Antimicrobial resistance (AMR) is a growing threat, significantly driven by horizontal gene transfer (HGT).
• Conjugative plasmids are key vectors for the rapid, cross-species dissemination and stable inheritance of AMR genes.
• Interventions targeting plasmid transmission or persistence offer a complementary approach to traditional antimicrobial therapies and infection control.

Purpose of the Study:

• To review druggable vulnerabilities in plasmid conjugation and maintenance mechanisms.
• To explore various strategies for inhibiting HGT and plasmid persistence.
• To assess the potential of HGT inhibition as a tool for combating AMR.

Main Methods:

• A narrative literature search focusing on recent mechanistic, ecological, and in vivo studies.
• Identification of vulnerabilities in conjugation processes (e.g., mating-pair formation, type IV secretion) and plasmid maintenance (e.g., replication, partitioning).
• Review of biological, chemical, metabolic, and genetic strategies aimed at inhibiting plasmid transfer or eliminating resistance elements.

Main Results:

• Identified druggable targets within conjugation machinery and plasmid maintenance systems.
• Cataloged diverse inhibitory strategies including biological antagonists, chemical inhibitors, and genetic approaches.
• Highlighted the progression of HGT inhibition from conceptualization to practical application.

Conclusions:

• Horizontal gene transfer inhibition is advancing towards actionable containment of antimicrobial resistance.
• Further progress requires mechanism-confirmed leads, standardized metrics, and rigorous safety evaluations.
• Near-term applications are anticipated as adjuncts to antimicrobial stewardship and infection prevention, reducing acquisition and carriage of resistance plasmids.