| Summary: | Commensal <i>Escherichia coli</i> with broad repertoire of virulence and antimicrobial resistance (AMR) genes pose serious public health risks as reservoirs of AMR and virulence. This study undertook whole genome characterization of commensal <i>E. coli</i> from food-producing animals in Uganda to investigate their genome variability (resistome and virulome). We established that the <i>E. coli</i> had high genomic diversity with 38 sequence types, 24 FimH types, and 33 O-antigen serotypes randomly distributed within three phylogroups (A, B1, and E). A greater proportion (≥93.65%) of the <i>E. coli</i> were resistant to amoxicillin/clavulanate and ampicillin antibiotics. The isolates were AmpC beta-lactamase producers dominated by <i>bla</i><sub>EC-15</sub> (71.88%) and <i>tet(A)</i> (20.31%) antimicrobial resistant genes besides a diverse armory of virulence-associated genes in the class of exotoxin, adhesins, iron uptake, and serine protease autotransporters which varied by host species. Cattle were found to be the major source of <i>E. coli</i> carrying Shiga toxin genes, whereas swine was the main source of <i>E. coli</i> carrying colicin-like <i>Usp</i> toxin gene. The study underscores the importance of livestock as the carrier of <i>E. coli</i> with antimicrobial resistance and a large repertoire of virulence traits with a potential of causing disease in animals and humans by acquiring more genetic traits.
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