Evidence of diversification and geographic separation in a lineage of Campylobacter jejuni co-circulating in cattle and humans

<i>Campylobacter jejuni</i>, a leading cause of gastroenteritis, is acquired by consuming contaminated food products or via direct contact with animal reservoirs like cattle and poultry. Prior studies have identified specific <i>C. jejuni</i> lineages such as sequence type (ST)-982 and ST-61, to be associated with cattle, while others are linked to chickens and other animal sources. Since cattle-associated lineages were more commonly resistant to tetracycline and detected in patients with a history of cattle contact, we performed comparative genomics on 61 cattle- and 175 human-derived strains collected during an overlapping time period in Michigan. Pangenome analyses and a core-gene phylogeny revealed a high degree of genomic similarity among cattle-associated lineages regardless of strain source, while a machine learning approach predicted that the ST-982 human strains originated from cattle. Further characterization of these closely related strains using high-quality SNP clustering demonstrated that the human and cattle strains differed by >260 SNPs. The cattle genomes also have less unique genes with fewer accessory and virulence genes than the human genomes, providing evidence for diversification within and adaptation to the cattle host. Comparing the core-gene MLST (cgMLST) profiles to those from 723 published ST-982 genomes identified multiple sequence clusters that varied in frequency by US region. Together, these data illustrate that genetically similar ST-982 strains are co-circulating in cattle and humans. They also suggest that clonal expansion of cattle-associated lineages may contribute to regional differences in genotype distributions and antibiotic resistance frequencies, which likely occur due to varying selective pressures present in each region.