Genome Analysis of Japanese Yersinia pseudotuberculosis Strains Isolated From Kawasaki Disease Patients and Other Sources and Their Phylogenetic Positions in the Global Y. pseudotuberculosis Population

Yersinia pseudotuberculosis (Ypt) is a gram-negative bacterium that infects both humans and animals primarily through fecal‒oral transmission. While Ypt causes acute gastroenteritis in humans, an association with Kawasaki disease (KD), a disease that primarily affects infants and young children and causes multisystemic vasculitis, has also been suspected. Although KD represents a significant health concern worldwide, the highest annual incidence rate is reported in Japan. Previously, a geographical origin-dependent population structure of Ypt comprising the Asian, transitional, and European clades was proposed. However, genomic data on KD-associated Ypt strains is currently unavailable. In this study, to analyze the phylogenetic and genomic features of KD-associated strains, we determined the whole-genome sequences of 35 Japanese Ypt strains, including 11 KD-associated strains, and constructed a genome set (n = 204) representing the global population of Ypt by adding publicly available Ypt genomes. In a phylogenetic analysis, all sequenced Japanese strains, including the KD-associated strains, belonged to the Asian clade, which appeared to be the ancestral clade of Ypt, and the KD-associated strains belonged to multiple lineages in this clade. Strains from patients with Far East scarlet-like fever (FESLF), a KD-related disease, also belonged to the Asian clade. Moreover, no KD strain-specific genes were identified in pan-genome-wide association study analyses. Notably, however, the gene encoding a superantigen called Yersinia pseudotuberculosis-derived mitogen (YPM) showed a distribution pattern highly biased to the Asian clade. Although further studies are needed, our results suggest that Asian clade strains may have a greater potential to trigger KD.