A pan-genome perspective on the evolutionary dynamics of polyphyly, virulence, and antibiotic resistance in serovar Mbandaka highlights emerging threats to public health and food safety posed by cloud gene families.

serovar Mbandaka, a prevalent foodborne pathogen, poses a threat to public health but remains poorly understood. We have determined the phylogenomic tree, genetic diversity, virulence, and antimicrobial resistance (AMR) profiles on a large genomic scale to elucidate the evolutionary dynamics within the Mbandaka pan-genome. The polyphyletic nature of this serovar is characterized by two distinct phylogenetic groups and inter-serovar recombination boundaries, that potentially arising from recombination events at the H2-antigen loci. The open pan-genome exhibited a flexible gene repertoire, with numerous cloud gene families involved in virulence and AMR. Extensive gene gain and loss observed at the terminal nodes of the phylogenetic tree indicate that Mbandaka individuals have undergone frequent gene turnover. The resulting changes in virulence and AMR genes potentially pose emerging threats to public health. We explored serovar conversion due to recombination of H-antigen loci, inter-serovar divergences in gene gain and loss, prophage-mediated acquisition of virulence factors, and the role of incompatibility group plasmids in acquiring resistance determinants as key molecular mechanisms driving the pathogenicity and antibiotic resistance of Mbandaka. Our work contributes to a comprehensive understanding of the complex mechanisms of pathogenesis and the ongoing evolutionary arms race with current therapeutic approaches in serovar Mbandaka.