Transmission of Multidrug-Resistant Salmonella enterica Subspecies enterica 4,[5],12:i:- Sequence Type 34 between Europe and the United States

ince the late 1990s, reports of an emerging mul- tidrug-resistant Salmonella enterica subspecies enterica serotype 4, [5],12:i:-strain have been published in Europe (1).This strain is a monophasic variant of Salmonella Typhimurium, predominantly resistant to ampicillin, streptomycin, sulfonamides, and tetracycline (ASSuT).Its rapid increase in North America after 1998 has also been described (2).However, precise knowledge of the time of introduction and the initial influx of clinical cases caused by this serotype in the United States is not available because of inconsistent reporting before 2004 (3).Previously, on the basis of high genetic similarity between Salmonella 4,[5],12:i:-sequence type (ST) 34 isolates from the United States and Europe and Salmonella Typhimurium strains from Europe, we suggested a European origin for the Salmonella 4,[5],12:i:-ST34 clade (4).With this study, we aimed to reconstruct a time-scaled phylogeny of the emerging ST34 clade by using a Bayesian modeling approach to determine its origin in United States. The StudyWe used publicly available whole-genome sequences of 1,431 Salmonella 4,[5],12:i:-ST34 isolates from the United States and Europe from 2008-2017, including sequences from 690 isolates from Europe (mainly from the United Kingdom and Denmark) and 741 isolates from multiple US states (Appendix 1, https://wwwnc.cdc.gov/EID/article/26/12/20-0336-App1.xlsx).We used BEAST version 1.8.4 (5) to estimate divergence times, mutation rates, and location trait transitions.We applied the modeling approach to 10 subsets of 112 sequences selected from the study population.These sequences represented 33% (474/1,431) of the study population and included 242 sequences from Europe (76% from humans, 8% from food products, 8% from livestock, and 8% from other sources) and 232 from the United States (62% from humans, 13% from food products, 21% from livestock, and 3% from other sources).Time-scaled phylogenies of each subset were reconstructed by using a general time-reversible nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock, and an exponential growth coalescent model with asymmetric trait transitions (Figure 1; Appendix 2 Figures 1-10, https://wwwnc.cdc.gov/EID/article/26/12/20-0336-App2.pdf).All time-scaled phylogenies presented similar topology to a maximum-likelihood phylogeny constructed by using all 1,431 study isolates (based on visual inspection; Appendix 2 Figure 11).Overall, averaged estimates from all subsets were in agreement as follows (Figure 2): the evolutionary rate was 3.64 × 10 -7 substitutions/site/year (95% highest posterior density [HPD] 2.65-4.64× 10 -7 ), which corresponds to an accumulation of ≈1-2 single-nucleotide Transmission of Multidrug-Resistant Salmonella enterica Subspecies enterica 4,[5],12:i:-Sequence Type 34 between Europe and the United States