Bacteriophage–plasmid interactions to limit antimicrobial resistance spread

Abstract

Antimicrobial resistance (AMR) is driven not only by antimicrobial use but also by the horizontal transfer of resistance genes between bacteria. Conjugative plasmids are key drivers of this process, facilitating the dissemination of antibiotic resistance genes across diverse bacterial populations. While efforts to address AMR have largely focused on developing new antimicrobials, strategies to restrict gene flow remain comparatively underexplored. Mobile genetic elements frequently compete for host occupancy, and exclusion mechanisms that limit their coexistence are widespread. These interactions suggest an opportunity to exploit natural competition between elements as a means to restrict horizontal gene transfer. In particular, bacteriophage–plasmid interactions provide a compelling model. For example, the bacteriophage B3 exclusion system strongly inhibits IncP plasmid transfer in Pseudomonas aeruginosa, demonstrating how phage mediated interference can act as a barrier to gene exchange. Harnessing such interactions may provide a complementary approach to limiting the spread of antimicrobial resistance. More broadly, understanding and leveraging natural barriers on gene flow could open new avenues for AMR control beyond conventional therapeutics.