Genomic Dissection Reveals Polyphyletic Origins and Recombination-Driven Diversification of O/K Antigen Loci in Foodborne Vibrio parahaemolyticus O4:KUT Strains

Vibrio parahaemolyticus is a leading cause of seafood-associated gastroenteritis worldwide. Traditional serotyping based on 13 O and 71 K antigens fails to classify many isolates, designated as K-untypable (KUT), whose genetic basis and evolutionary dynamics remain unclear. In this study, we conducted whole-genome sequencing of 47 O4:KUT strains from 40 clinical and 7 retail aquatic products (snail, river shrimp, Macrobrachium rosenbergii, etc.) to decipher the genomic diversity and structural variation in their O/K antigen loci. Phylogenomic analysis revealed a polyphyletic population structure spanning multiple sequence types, with O/K antigen loci classified into 13 distinct structural types comprising 149 biosynthetic genes. These clusters exhibited mosaic architectures and varied functional profiles. Notably, pervasive phylogenetic incongruence and robust recombination signals identified horizontal gene transfer as the primary mechanism driving O/K antigen loci diversification. Our findings reveal the evolutionary mechanisms of the foodborne O4:KUT serotype prevalent in local seafood and clinical samples from Huzhou, China, and provide a preliminary gene-signature framework that may inform the future development of molecular serotyping assays.