Emergence of multidrug-resistant blaCTX-M-65/gyrA_D87Y clones among the circulating Salmonella Infantis population in Mexico

Global dissemination of emergent multidrug-resistant (MDR) Salmonella Infantis (ESI) is of great public health concern. ESI exhibits increased virulence and MDR phenotypes, features conferred by a conjugative megaplasmid (pESI-like). In Mexico, the potential circulation of ESI clones has been overlooked. This study assessed the structure, diversity, genomic features and transmission dynamics of Salmonella Infantis isolates ( n =191) from cattle, pigs, chickens, humans, surface waters and the environment from surveys conducted by research laboratories and government agencies in the 2008–2024 timeframe. Three genomic approaches were implemented: blast analysis, SNP-based phylogenetic analysis and ancestral state reconstruction analysis. The phylogeny divided the population into two divergent sublineages, based on the presence/absence of pESI-like plasmids. The apparently recent and massive acquisition of these plasmids had a profound impact at the population level, changing the proportion of isolates with MDR genotypes from 0 to 68%. Although ESI was mostly associated with chickens, it was also present in surface waters. In fact, our ancestral state reconstruction analysis showed that ESI likely evolved from surface water ancestors within poultry production environments. Most locally circulating ESI clones (73%) harbour resistance factors to 6–8 antibiotic classes, including extended-spectrum cephalosporins ( bla CTX-M-65 ) and fluoroquinolones ( gyrA D87Y mutation), a feature shared with global ESI variants that we coined as CTX-M-gyrA 6-8. Control measures are urgently needed to prevent further dissemination of ESI, as well as the systematic surveillance of CTX-M-gyrA 6-8 clones, particularly in poultry, to reduce the risk of human exposure to this potentially deadly pathogen.