Large-scale whole-genome sequencing of animal clinical Salmonella enterica demonstrates relatedness to human cases.

Since 2017, the Veterinary Laboratory Investigation and Response Network (Vet-LIRN) has conducted monitoring of antibiotic-resistant bacteria from sick animals, collecting a diverse set of bacterial pathogens from various animal species. Isolates undergo antimicrobial susceptibility testing, with a subset undergoing whole-genome sequencing (WGS). For this work, we sequenced and analyzed 3443 Salmonella enterica genomes collected by thirty veterinary diagnostic laboratories from 2017 to 2025 as part of Vet-LIRN's antimicrobial resistance (AMR) monitoring. While the majority of these clinical isolates were from cattle (28.6%), horses (23.1%), pigs (21.6%), chickens (9.5%), and dogs (4.5%), they originated from over one hundred distinct animal species. Most isolates (67.0%), were within twenty single nucleotide polymorphisms of at least one human clinical isolate, indicating a high degree of relatedness to bacteria causing human illness. Furthermore, over one hundred different resistance mechanisms were identified, conferring resistance to twelve different drug classes, including those critically important to human treatment such as cephalosporins and fluoroquinolones. Together, these data demonstrate that drug-resistant Salmonella from sick animals are often closely related to strains found in humans, underscoring the need for a One Health surveillance approach to safeguard animal and public health.