Genome Variation and Molecular Epidemiology of Salmonella enterica Serovar Typhimurium Pathovariants

Abstract

Salmonella enterica serovar Typhimurium is one of approximately 2,500 distinct serovars of the genus Salmonella but is exceptional in its wide distribution in the environment, livestock, and wild animals. S Typhimurium causes a large proportion of nontyphoidal Salmonella (NTS) infections, accounting for a quarter of infections, second only to S. enterica serovar Enteritidis in incidence. S Typhimurium was once considered the archetypal broad-host-range Salmonella serovar due to its wide distribution in livestock and wild animals, and much of what we know of the interaction of Salmonella with the host comes from research using a small number of laboratory strains of the serovar (LT2, SL1344, and ATCC 14028). But it has become clear that these strains do not reflect the genotypic or phenotypic diversity of S Typhimurium. Here, we review the epidemiological record of S Typhimurium and studies of the host-pathogen interactions of diverse strains of S Typhimurium. We present the concept of distinct pathovariants of S Typhimurium that exhibit diversity of host range, distribution in the environment, pathogenicity, and risk to food safety. We review recent evidence from whole-genome sequencing that has revealed the extent of genomic diversity of S Typhimurium pathovariants, the genomic basis of differences in the level of risk to human and animal health, and the molecular epidemiology of prominent strains. An improved understanding of the impact of genome variation of bacterial pathogens on pathogen-host and pathogen-environment interactions has the potential to improve quantitative risk assessment and reveal how new pathogens evolve.

Keywords: Salmonella; Typhimurium; epidemiology; genomics; host adaptation; phylogenetics; virulence.

FIG 1

Host range and plausible transmission routes of major S. Typhimurium phage types in humans, pigs, cattle, wild avian species, ducks, and poultry. Dominant phage types are indicated in boldface, and minority phage types in italics. Arrow colors matched to each phage type indicate probable transmission routes based on the epidemiological record but may not include all possible routes. Line thickness indicates relative level of transmission, and the question mark a hypothetical route of transmission of ST313.

FIG 2

Phylogenetic relationships of Salmonella enterica subspecies I serovars and S. Typhimurium strains. Maximum-likelihood trees of 15 S. enterica subspecies I serovars (A) and 194 S. Typhimurium strains (B) based on sequence variation in the core genome. Trees are midpoint rooted (filled black circle). (B) The inner circle indicates the source animal host species for each S. Typhimurium strain, with color code as shown in the key. The outer circle indicates ST19 (black line), other STs (gray box), and strains with an unassigned ST (line break). Strains with a published complete, closed genome sequence are indicated by small black circles at leaf nodes, and the names of key strains are in italics. The locations of key clades are indicated with boldface black font. The positions of two major clades containing strains with distinct epidemiology are indicated near the root (# and *).