Genomic characterization of Enterotoxigenic Escherichia coli lineage 2 (CS2 + CS3) by long-read sequencing reveals distinct lineage-specific genome organization
摘要
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in children, adults and travellers in endemic regions. ETEC pathogenesis is mediated by heat-labile (LT) and heat-stable (ST) enterotoxins together with colonization factors. In this study, we characterized the chromosomal and plasmid features of twelve ETEC lineage 2 (L2) isolates, including five isolates sequenced by long-read PacBio technology and reported for the first time in this study, and seven publicly available complete genomes. Comparative genomic analysis revealed a highly conserved chromosomal backbone and two core plasmids, with the CS2 operon uniquely integrated into the chromosome, while other virulence determinants, including LT, ST, CS3, EatA, CS21, and EtpBAC remained plasmid-encoded. Fusion and consolidation of lineage 1-like plasmids produced a streamlined plasmidome in L2, preserving essential virulence genes while occasionally incorporating antibiotic resistance determinants. Phage-like plasmids were identified sporadically, highlighting ongoing horizontal gene acquisition. These findings demonstrate that ETEC L2 employs a hybrid virulence architecture combining chromosomal fixation of a key colonization factor with plasmid-mediated accessory traits, potentially enhancing stability and transmissibility. The study provides new insights into the genomic organization, evolutionary dynamics, and pathogenic potential of this emerging ETEC lineage.