Genetic exchange networks bridge mobile DNA vehicles in the bacterial pathogen Listeria monocytogenes.

Listeria monocytogenes (Lm) is an opportunistic foodborne pathogen responsible for gastrointestinal illnesses and life-threatening invasive infections. Antimicrobial resistance, virulence, and rapid adaptation to stressful environments in Lm lie in part on its mobile genetic elements (MGE). Here, we aim to characterize the MGE pool of a clinical Lm population using 936 genomes sampled across New York State (USA) from 2000 - 2021. We built a network based on sequence homology among putative MGEs. Within the network are communities of densely interconnected MGEs indicating high genetic similarity in their DNA regions. Although most connections involve the same MGE type, subsets within the network link different MGE types (plasmid-transposon, phage-plasmid). Phages and transposons did not share any genetic connections, suggesting impermeable barriers of exchange between them. Genes involved in stress tolerance are overrepresented in plasmids and transposons, and are mobile between vehicles. Analysis of long-read sequences of a subset of our dataset (n = 37) and publicly available, globally distributed complete genomes (n = 425) recapitulated the MGE connections we observed. Our findings reveal a structured but interconnected network of genetic exchanges between different mobile DNA vehicles. Genetic exchanges between MGEs shape Lm intra-species variation, adaptive potential, and rapid dissemination of clinically relevant traits at short timescales.