Virulence and antimicrobial resistance in Salmonella enterica serovar Typhimurium: a One Health perspective on therapeutic and vaccine targets.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major non-typhoidal Salmonella serovar associated with a substantial global burden of foodborne and invasive infections. Its transmission across human, animal, food, and environmental interfaces highlights its significance its relevance within a One Health framework. The pathogenicity of S. Typhimurium is mediated by multiple virulence determinants, including Salmonella pathogenicity islands (SPI-1 and SPI-2), type III secretion systems (T3SS), fimbrial adhesins, and biofilm formation, which contribute to host cell invasion, intracellular survival, and persistence. The increasing prevalence of antimicrobial resistance (AMR) in S. Typhimurium is driven by horizontal gene transfer and chromosomal mutations, involving resistance determinants such as β-lactamase genes (blaCTX-M, blaVIM), plasmid-mediated quinolone resistance genes (qnr), colistin resistance genes (mcr), and mutations in target genes (e.g., gyrA, gyrB). These mechanisms have reduced the effectiveness of commonly used antibiotics and contributed to the emergence of multidrug-resistant strains. This review synthesizes current knowledge on the epidemiology, transmission dynamics, virulence mechanisms, and AMR profiles of S. Typhimurium, including global burden indicators such as Disability-Adjusted Life Years (DALYs) and region-specific trends in India. Current therapeutic approaches and vaccine candidates are also evaluated, highlighting existing limitations and research gaps. Emphasis is placed on the interaction between virulence and AMR and the identification of conserved molecular targets to support the development of effective interventions within a One Health framework.