Wave succession in the pandemic clone of Vibrio parahaemolyticus driven by gene loss

While spontaneous mutation and gene acquisition are well-established drivers of pathogen adaptation, the role of gene loss remains underexplored. Here we investigated the emergence and diversification of the pandemic clone of Vibrio parahaemolyticus through large-scale phylogenomic analysis of 8,684 global isolates. The pandemic clone rapidly acquired multiple marker genes and genomic islands, subsequently diverging into successive sublineages mediating independent waves of cross-country transmission, as also observed in Vibrio cholerae. Wave succession in the last two decades was driven by loss of putrescine utilization (Puu) genes, conferring phenotypic advantages for environmental adaptation (enhanced biofilm formation) and human transmission (increased cell adhesion and intestinal colonization and reduced virulence), consistent with the virulence trade-off hypothesis. We identified Puu-gene loss in several bacterial genera, with effects on biofilm and adhesion replicated in V. cholerae and Escherichia coli, suggesting convergent evolution and universal phenotypic effects. Our results highlight the indispensable role of gene loss in bacterial pathogen adaptation. A combination of large-scale phylogenomic analysis, mouse lethality experiments and bacterial growth assays shows that gene loss in the putrescine utilization pathway has enhanced biofilm formation and transmission-related characteristics in the pandemic clone of a bacterial pathogen, Vibrio parahaemolyticus, promoting successive waves of global transmission events.