Research Projects

Plasmids often carry antimicrobial resistance (AMR) genes, which are non-essential for the host but can provide a fitness advantage to the hosts harbouring them when antibiotics are present. Since the plasmids utilize host metabolic machinery, harbouring them can incur a significant metabolic burden on the host. However, plasmids are still maintained within microbial populations and are frequently found in clinical isolates of different pathogens. This can be due to compensatory mutations in host genomes that can decrease the metabolic burden of the plasmids. However, in the presence of antibiotics, pathogens harbouring such plasmids carrying AMR genes can enrich in frequency resulting in a chronic sustained infection that could sometimes result in death. In nature, pathogens are a part of polymicrobial communities, where biotic interactions can significantly influence their evolutionary trajectories. Hence, a comprehensive understanding of plasmid-borne AMR in a polymicrobial community, where the host experiences multiple biotic interactions, is essential to achieve a holistic perspective of AMR spread and maintenance. Here, we propose an evolution experiment to study the influence bacterial predation on the evolutionary dynamics of conjugative plasmid, carrying AMR genes when coevolving with the host. Laboratory evolution experiments provide insights into novel pathways that can be explored by the plasmid and the host when the host is under the combined threat of predator and antibiotics. To do so, we plan to coevolve a broad host-ranged, conjugative plasmid, RP4, inside its host, E. coli in the presence of a soil-dwelling bacterial predator, M. xanthus. The three partners will coevolve in an environment containing subinhibitory concentrations of antibiotics for several generations. Such three-partner laboratory evolution experiments will allow us to track the evolutionary trajectory of each partners using genomics and genetics as tools to get a deeper understanding of the molecular basis of their adaptations in terms of 1) the influence of predation on the transmissibility of AMR carrying plasmids 2) compensations for fitness cost in the host to allow maintenance of conjugative plasmids, and 3) trade-off between AMR and predation resistance in the host bacterium. This study will not only provide a deeper insight into the novel mechanisms of plasmid mediated spread of AMR but will also highlight the influence of biotic interactions on the spread of AMR in polymicrobial communities. Previous studies from the group have shown that the presence of M. xanthus, which is ubiquitously found in soil communities can also significantly influence the local antibiotic resistome of complex soil communities. Thus, together, this study will provide a broader understanding of both the maintenance and spread of plasmid-borne AMR in polymicrobial communities, where biotic interactions engaging the host also influence the evolutionary trajectory of plasmids.