Food animals are known reservoirs of multidrug-resistant (MDR) Escherichia coli, but information regarding the factors influencing colonization by these organisms is lacking. Here we report the genomic analysis of 66 MDR E. coli isolates from non-redundant veal calf fecal samples. Genes conferring resistance to
aminoglycosides, β-
lactams,
sulfonamides, and
tetracyclines were the most frequent antimicrobial resistance genes (ARGs) detected and included those that confer resistance to clinically significant
antibiotics (blaCMY-2, blaCTX-M, mph(A), erm(B), aac(6')Ib-cr, and qnrS1). Co-occurrence analyses indicated that multiple ARGs significantly co-occurred with each other, and with
metal and
biocide resistance genes (MRGs and BRGs). Genomic analysis also indicated that the MDR E. coli isolated from veal calves were highly diverse. The most frequently detected genotype was phylogroup A-ST
Cplx 10. A high percentage of isolates (50%) were identified as sequence types that are the causative agents of extra-intestinal
infections (ExPECs), such as ST69, ST410, ST117, ST88, ST617, ST648, ST10, ST58, and ST167, and an appreciable number of these isolates encoded
virulence factors involved in the colonization and
infection of the human urinary tract. There was a significant difference in the presence of multiple accessory
virulence factors (VFs) between MDR and susceptible strains. VFs associated with enterohemorrhagic
infections, such as stx, tir, and eae, were more likely to be harbored by antimicrobial-susceptible strains, while factors associated with extraintestinal
infections such as the sit system,
aerobactin, and pap fimbriae genes were more likely to be encoded in resistant strains. A comparative analysis of SNPs between strains indicated that several closely related strains were recovered from animals on different farms indicating the potential for resistant strains to circulate among farms. These results indicate that veal calves are a reservoir for a diverse group of MDR E. coli that harbor various resistance genes and
virulence factors associated with human
infections. Evidence of co-occurrence of ARGs with MRGs, BRGs, and
iron-scavenging genes (sit and
aerobactin) may lead to management strategies for reducing colonization of resistant bacteria in the calf gut.