Host adaptation in Salmonella enterica serovar Typhimurium: population structure, pathovariants, and genomic mechanisms.

Salmonella enterica serovar Typhimurium is a major zoonotic pathogen of global concern to human and animal health. With its broad host range, this serovar can colonize humans as well as domesticated and wild animals. Although historically considered a model host-generalist pathogen, whole-genome sequencing (WGS) has uncovered substantial genetic diversity and the emergence of multiple host-adapted pathovariants within this serovar. In this minireview, we delineate the population structure of S. Typhimurium across diverse host species and identify the lineages/pathovariants specifically adapted to avian hosts (e.g., passerines, pigeons, ducks, geese, larids, and water birds) and those adapted to non-avian hosts (e.g., humans). We further discuss the genetic mechanisms underlying host adaptation of S. Typhimurium pathovariants, including genome degradation through point mutations and insertions/deletions, as well as the acquisition of prophages or antimicrobial resistance genes via horizontal gene transfer. The ongoing emergence of host-adapted pathovariants in zoonotic pathogens such as S. Typhimurium underscores the importance of high-resolution, WGS-based subtyping approaches for precise pathogen identification and source attribution. Moreover, elucidating the genetic mechanisms driving host adaptation of zoonotic pathogens at the strain level is essential for informing targeted strategies for surveillance, prevention, and control.