A one health genomic analysis reveals shared Salmonella Newport lineages across human, animal, and environmental reservoirs

Salmonella enterica serovar Newport ( Salmonella Newport) is an important foodborne pathogen circulating across human, animal, and environmental reservoirs. Despite increasing reports of multidrug resistance, the extent of cross-sector transmission and shared lineages remains poorly understood. Genomic epidemiology offers a powerful approach to elucidate transmission dynamics and track the movement of high-risk clones across the One Health interface. This study investigated antimicrobial resistance, plasmid content, and genetic relatedness of Salmonella Newport genomes from human, animal and environmental sources. We conducted a cross-sectional study among 97 Salmonella Newport genomes from animal, food, clinical, and environmental sources collected across 17 U.S. states in 2023. Genomic data were retrieved from NCBI and analyzed to identify resistance genes and plasmid profiles. Genetic relatedness among isolates was determined using multi-locus sequence typing and single nucleotide polymorphism (SNP). Genotypic resistance was observed to sulfamethoxazole (11.3%; 11/97), tetracycline (8.2%; 8/97), and chloramphenicol (7.2%; 7/97). Various β-lactam resistance genes were detected including bla CARB-2 (n=3), bla CMY (n=3), and bla CTX-M-15 (n=1). The bla CARB-2 and bla CMY genes were carried by animal-derived isolates, whereas bla CTX-M-15 was identified in a human isolate. Twelve isolates were multidrug resistant (MDR); resistant to three or more drug classes, with MDR strongly associated with isolate source (Fisher’s exact test, p=0.000243). Twenty plasmid types were identified, with IncFII(p96A) and IncFII(S) (n = 8 each) present across sources. SNP analysis revealed close genetic relatedness between human and farm soil isolates from Delaware, differing by 11 SNPs, suggesting potential environmental or cross-reservoir transmission. The detection of MDR Salmonella Newport across human, animal, and environmental sources, coupled with strong associations between MDR profiles and isolate origin, highlights the widespread distribution of AMR across diverse ecological settings. The presence of plasmids highlights the potential for horizontal gene transfer to accelerate the spread of resistance across reservoirs. These findings reinforce the importance of a coordinated One Health approach that strengthens surveillance. Continued genomic surveillance integrated with epidemiological and phenotypic data is important for understanding the emergence of MDR lineages and inform public health decision-making.