Genomic diversity of diarrheagenic multidrug-resistant Escherichia coli across asymptomatic children and livestock in Nairobi, Kenya

Diarrheagenic <i>Escherichia coli</i> represents a critical public health threat, yet their genomic characteristics in community settings remain poorly described. We sequenced 77 multidrug-resistant isolates from children (n = 59), livestock (n = 17), and food (n = 1) in peri-urban Nairobi, Kenya. Phylogenetic analysis revealed polyphyletic diversity across phylogroups and sequence types without host-specific clustering. We detected high-risk lineages ST69 (n = 5) and ST131 (n = 2) among children. Nearly all isolates carried extended-spectrum β-lactamase genes, including <i>bla</i>_CTX-M-15 and <i>bla</i>_OXA-1, with resistance spanning nine antibiotic classes. Network analysis revealed a stable multidrug-resistance cluster (<i>bla</i>_TEM-1B, <i>aph(3)-Ib</i>, <i>aph(6)-Id</i>, <i>sul2</i>, <i>tetA</i>) shared across hosts. Virulence-associated gene profiling showed 34 enteric-associated determinants, with children’s isolates carrying significantly more genes than livestock (mean 6.4 vs. 4.2, p = 0.001). The presence of virulent, multidrug-resistant lineages in apparently healthy community carriers highlights a potential reservoir of multidrug-resistant diarrheagenic-associated pathogenic potential outside hospitals. These findings underscore urgent need for genomic surveillance, stewardship and WASH to interrupt transmission of high-risk <i>E. coli</i> clones.