Colibactin (pks) carriage in Escherichia coli is associated with lineage restriction, reduced plasmid burden, and lower antimicrobial resistance

The colibactin pks genomic island of Escherichia coli is a chromosomally integrated secondary metabolite locus implicated in host–microbe interactions and colorectal carcinogenesis. Although pks distribution has been linked to specific E. coli lineages, its relationship with plasmid burden, antimicrobial resistance (AMR), and genome-wide accessory gene structure remains incompletely resolved at population scale. Here, we analyzed 9,700 curated E. coli genomes from BV-BRC and identified 498 genomes carrying complete or near-complete canonical pks loci. pks -positive genomes were strongly enriched in phylogroup B2 and concentrated within a limited number of sequence types, including ST73, ST95, ST127, and ST12. Compared with pks- negative genomes, pks -positive genomes carried fewer AMR genes and fewer plasmid replicons. This pattern persisted in phylogroup B2-controlled comparisons, although sequence-type structure remained an important potential contributor. Synteny and flanking-region analyses showed strong conservation of the internal clb gene cluster together with recurrent conservation of the surrounding chromosomal neighborhood, consistent with positional stability of canonical pks loci. Pangenome reconstruction of B2-matched genomes revealed that pks -positive genomes had a smaller total pangenome and accessory gene compartment, but a larger core genome, than pks- negative genomes. Together, these findings indicate that canonical pks carriage marks a lineage-restricted and genomically conserved E. coli subpopulation associated with reduced plasmid and AMR burden. These associations support a model in which colibactin-positive lineages differ from multidrug-resistant plasmid-rich lineages in their accessory genome architecture, although experimental studies remain required to define the underlying mechanisms.