Long-Term Genomic Surveillance Unveils Key Drivers of Salmonella Contamination and Antimicrobial Resistance Dynamics in Surface Waters from Central Mexico

We analyzed the prevalence dynamics, genetic diversity, and AMR dynamics of Salmonella spp. (SAL) across surface waters (SuWa) in Central Mexico. On-site, 953 samples (10 L each) from 49 watersheds were collected in 24 sampling rounds (2019–2024) using the modified Moore swab technique. SAL was isolated and identified using conventional microbiological procedures and sequenced on Illumina platforms. Overall, the prevalence of SAL was 54%. The top 10 serovars (e.g., Agona, Newport, Infantis, Typhimurium) accounted for over 50% of the population and exhibited robust longitudinal persistence and clonal expansion across distant effluents. Resistance to older antibiotics was frequently observed (e.g., tetracycline, streptomycin, and chloramphenicol: 36%, 33%, and 24%, respectively), exhibiting stationary dynamics over the surveillance timeframe. Remarkably, 12% of the isolates showed resistance to azithromycin, displaying a transient pandemic-associated retention in 2021 that matched intense community-level clinical antibiotic pressures. One-third of the isolates exhibited multidrug-resistant (MDR) phenotypes, matching the observed genotypes (Cohen’s κ = 0.8085, P < 0.0001) and showing that the acquired resistome is highly functional. Generalized linear mixed models showed that climatic cycles and water pH are major drivers of SAL contamination, whereas persistent anthropogenic pressures reintroduce the pathogen and select for MDR traits, contributing to the MDR burden stability. Multivariate analyses further confirmed this resilience of the SAL resistome, although local hydrological and environmental heterogeneities introduce a diverse array of genetic determinants into SuWa, fueling the broad multivariate dispersion observed across regions. These findings present critical One Health concerns, underscoring the need to implement risk-directed genomic environmental surveillance.