Characterization of a Listeria monocytogenes plasmid with antibiotic and stress resistance genes

Listeriosis is a predominantly foodborne infection causing severe, invasive disease in the immunocompromised, with the causative agent being Listeria monocytogenes. While L. monocytogenes possesses innate resistance to several classes of antibiotics, acquired antibiotic resistance is low compared with other foodborne pathogens. Conversely, plasmids possessing stress tolerance mechanisms are common and contribute to their ability to persist in food production environments. However, very few have been identified, which also carry antibiotic resistance genes, particularly multidrug resistance regions. We scanned a UK collection of L. monocytogenes genomes and detected an isolate with the dfrD, lnuG and mphB genes, encoding predicted resistance to trimethoprim, lincosamides and macrolides, respectively. This isolate also possessed a Listeria repA family plasmid replication gene, as well as multiple chromosomal and plasmid-associated stress tolerance factors. Long-read sequencing confirmed the presence of a single 120,420 bp plasmid, which notably is a composite of a highly conserved Listeria plasmid backbone with a novel 35 kb resistance region. Comparative genomic analyses revealed that the plasmid-borne resistance region was likely acquired from other Gram-positive species over several events. The island containing the lnuG and mphB genes has links to porcine and bovine origins, while the dfrD gene is located on a Tn3-like transposon associated with multiple resistance genes, and both elements can move to the chromosome of L. monocytogenes strains from food and human disease. This work furthers the understanding of plasmid-mediated antibiotic resistance as well as the wider circulation of mobile genetic elements among L. monocytogenes and other bacterial species within the food chain.