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Antimicrobial resistance (AMR) has important implications for the continued use of antibiotics to control infectious diseases in both beef cattle and humans. AMR along the One Health continuum of the beef production system is largely unknown. Here, whole genomes of presumptive extended-spectrum β-lactamase  E. coli  (ESBL-EC) from cattle feces ( n  = 40), feedlot catch basins ( n  = 42), surrounding streams ( n  = 21), a beef processing plant ( n  = 4), municipal sewage ( n  = 30), and clinical patients ( n  = 25) are described. ESBL-EC were isolated from ceftriaxone selective plates and subcultured on ampicillin selective plates. Agreement of genotype-phenotype prediction of AMR ranged from 93.2% for ampicillin to 100% for neomycin, trimethoprim/sulfamethoxazole, and enrofloxacin resistance. Overall, β-lactam (100%;  bla EC , bla TEM-1 , bla SHV , bla OXA , bla CTX-M-  ), tetracycline (90.1%;  tet(A), tet(B) ) and folate synthesis ( sul2 ) antimicrobial resistance genes (ARGs) were most prevalent. The ARGs  tet(C), tet(M), tet(32),   bla CTX-M-1 , bla CTX-M-14  ,  bla OXA-1 , dfrA18, dfrA19, catB3 , and  catB4  were exclusive to human sources, while  bla TEM-150  ,  bla SHV-11–12   ,   dfrA12, cmlA1 , and  cmlA5  were exclusive to beef cattle sources. Frequently encountered virulence factors across all sources included adhesion and type II and III secretion systems, while IncFIB(AP001918) and IncFII plasmids were also common. Specificity and prevalence of ARGs between cattle-sourced and human-sourced presumptive ESBL-EC likely reflect differences in antimicrobial use in cattle and humans. Comparative genomics revealed phylogenetically distinct clusters for isolates from human vs. cattle sources, implying that human infections caused by ESBL-EC in this region might not originate from beef production sources.

microorganisms

Whole Genome Sequencing Differentiates Presumptive Extended Spectrum Beta-Lactamase Producing Escherichia coli along Segments of the One Health Continuum