title: 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 entericaserovar 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 315S 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 Salmonellafrom 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.
authors.affiliation: Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark Center for Biological Sequence Analysis, Department of System Biology, Technical University of Denmark, Kgs. Lyngby, Denmark pile@food.dtu.dk.
authors.forename: Pimlapas
authors.initials: P
authors.lastname: Leekitcharoenphon
authors.affiliation: Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Rene S
authors.initials: RS
authors.lastname: Hendriksen
authors.affiliation: Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Centre National de Référence des Salmonella, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Le Hello
authors.affiliation: Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Centre National de Référence des Salmonella, Paris, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.affiliation: Technical University of Denmark, National Food Institute, Søborg, Denmark.
authors.forename: Dorte Lau
authors.initials: DL
authors.lastname: Baggesen
authors.affiliation: Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Jun
authors.affiliation: Center for Biological Sequence Analysis, Department of System Biology, Technical University of Denmark, Kgs. Lyngby, Denmark Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
authors.forename: David W
authors.identifier: http://orcid.org/0000-0003-3632-5512
authors.initials: DW
authors.lastname: Ussery
authors.affiliation: Center for Biological Sequence Analysis, Department of System Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Lund
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Aarestrup
mesh_terms: D000818:Animals; D024901:Drug Resistance, Multiple, Bacterial; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D005838:Genotype; D014943:Global Health; D006801:Humans; D017720:Molecular Epidemiology; D058889:Molecular Typing; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D012480:Salmonella Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D012481:Salmonella Infections, Animal / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D012486:Salmonella typhimurium / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D062211:Spatio-Temporal Analysis; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission