Global survey of extraintestinal pathogenic Escherichia coli identifies stable serogroup-virulence-resistance linkages

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of urinary tract infections, sepsis, and neonatal meningitis globally. However, global patterns linking O-serogroups, sequence types (STs), virulence, and antimicrobial resistance (AMR) remain poorly resolved. We analyzed 12,220 ExPEC genomes, including 12,160 publicly available genomes retrieved from the NCBI database and 60 representative isolates collected and sequenced in this study. Serogroups were assigned by in silico wzm/wzt/wzx/wzy and fliC gene analysis, and phylogenies constructed using maximum likelihood methods. Virulence and antibiotic resistance genes were annotated with the Virulence Factor Database and the Comprehensive Antibiotic Resistance Database. A set of ExPEC isolates collected from China was tested phenotypically for motility, iron acquisition and growth assays under standardized conditions. We identified 199 O-serogroups from the 12,220 genomes, with 17 dominant types accounting for 83% of isolates. O25 (30.75%) was globally prevalent, while O101 was more prevalent than O25 in China and India. Most of the isolates were from urine (44.49%) and blood (26.80%) as primary sources. Phylogenetic analysis revealed 52 clusters with stable serogroup-ST associations (e.g., O25-ST131, O2/O6-ST73). Virulence analysis uncovered 383 genes, with a conserved 24-gene core encoding adhesion and iron uptake genes. Resistance profiling revealed 308 genes, dominated by β-lactamases and efflux regulators. Integrated analysis identified iron acquisition (Vir_2) and efflux-mediated resistance (Res_5) as key genomic traits of high-risk serogroups, supported by phenotypic assays showing correlated motility and iron uptake patterns. We propose a genomic survey that integrates serogroup profiling with virulence-resistance gene-content clusters to resolve ExPEC population structure and functional convergence. These insights may guide the rational development of next-generation ExPEC vaccines and precision surveillance strategies.