Global Genomic Epidemiology of Salmonella enterica Serovar Typhimurium DT104

Abstract

It has been 30 years since the initial emergence and subsequent rapid global spread of multidrug-resistant Salmonella enterica serovar Typhimurium DT104 (MDR DT104). Nonetheless, its origin and transmission route have never been revealed. We used whole-genome sequencing (WGS) and temporally structured sequence analysis within a Bayesian framework to reconstruct temporal and spatial phylogenetic trees and estimate the rates of mutation and divergence times of 315 S. Typhimurium DT104 isolates sampled from 1969 to 2012 from 21 countries on six continents. DT104 was estimated to have emerged initially as antimicrobial susceptible in ∼1948 (95% credible interval [CI], 1934 to 1962) and later became MDR DT104 in ∼1972 (95% CI, 1972 to 1988) through horizontal transfer of the 13-kb Salmonella genomic island 1 (SGI1) MDR region into susceptible strains already containing SGI1. This was followed by multiple transmission events, initially from central Europe and later between several European countries. An independent transmission to the United States and another to Japan occurred, and from there MDR DT104 was probably transmitted to Taiwan and Canada. An independent acquisition of resistance genes took place in Thailand in ∼1975 (95% CI, 1975 to 1990). In Denmark, WGS analysis provided evidence for transmission of the organism between herds of animals. Interestingly, the demographic history of Danish MDR DT104 provided evidence for the success of the program to eradicate Salmonella from pig herds in Denmark from 1996 to 2000. The results from this study refute several hypotheses on the evolution of DT104 and suggest that WGS may be useful in monitoring emerging clones and devising strategies for prevention of Salmonella infections.

Genomic and phylogenetic analysis ofSalmonellaTyphimurium and its monophasic variants responsible for invasive endemic infections in Colombia

“…The clade shared high core genome similarity with a contextual DT104 genome from Scotland. From the identity of AMR genotype and phenotype and the estimated year of MRCA, we infer that the cluster 7 clade belonged to the global pandemic of MDR DT104, which spread across Europe, Asia and America from the 1970s [59].…”

“…The MDR phenotype of cluster 7 was associated with two AMR gene patterns: A clade resistance to ampicillin, chloramphenicol, streptomycin, and tetracycline was related to the presence of aadA2, blaCARB-2, floR, tet(A) and tet(G); and the other clade was resistant to ampicillin, tetracycline and trimethoprim carried aph(3')-Ia, blaOXA-2, dfrA29, mphB, sul1, and tet(A). The former clade shared the similar AMR phenotype and genotype as the MDR DT104 that emerged globally in the 1990s, which also carried the aadA, floR, sul1 and tet(G) genes [59].…”

Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation

“…Cattle isolates were in both first order clades (11 in clade α 7 in clade β ), but in clade β they had a relatively limited distribution with five of the isolates from a subclade containing the DT204/49 complex of strains associated with a cattle associated epidemic in the 1970's 8 . Clade α contained strains from several previously described epidemics in livestock animal species, including in pigs (α12, U288) 17 , two clades associated with recent pandemic clonal groups associated with pigs, cattle and poultry (α17, monophasic Typhimurium ST34 and α15, DT104) [18][19][20] , and potentially epidemic clades not previously described in the literature, consisting of isolates from pigs, cattle and poultry (α8 6 and α11). Clade-β was characterised by many long internal branches, indicative of a relatively high level of sequence divergence, relative to those in Clade-α.…”

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations

“…The emergence and dispersal of AMR Salmonella are particularly problematic, due to (i) the fact that nontyphoidal Salmonella represents one of the most common causes of foodborne disease cases and associated deaths worldwide (23) and (ii) reports on the emergence and dispersal of different multidrug-resistant Salmonella strains (e.g., Salmonella Typhimurium DT104) (24)(25)(26). Studies of the relationships between AMR determinants and MDR strains found in humans and animals are often confounded by the selection of the isolates included in a given study, in which human and animal isolates may be of different serotypes, geographical locations, or temporal intervals.…”