A multidrug-resistant Salmonella enterica serotype Typhimurium DT104 lineage circulating among humans and cattle in the United States lost the ability to produce pertussis-like toxin ArtAB in close temporal proximity to the global DT104 epidemic

Salmonella enterica subspecies enterica serotype Typhimurium phage type DT104 (DT104) can infect both humans and animals and is often multidrug-resistant (MDR). Previous studies have indicated that, unlike most S. Typhimurium, the overwhelming majority of DT104 strains produce a pertussis-like toxin, ArtAB, via prophage-encoded artAB ; however, DT104 that lack artAB have been described on occasion. Here, we identify a MDR DT104 lineage circulating among humans and cattle in the United States, which lacks artAB (i.e., the "U.S. artAB -negative major clade"; n = 41 genomes). Unlike most other bovine- and human-associated DT104 strains from the U.S. ( n = 219 total genomes), which harbor artAB on prophage Gifsy-1 ( n = 167), members of the U.S. artAB -negative major clade lack Gifsy-1, as well as anti-inflammatory effector gogB . The U.S. artAB -negative major clade was predicted to have lost artAB , Gifsy-1, and gogB circa 1993-1995 (95% highest posterior density interval 1989.5-1997.7), in close temporal proximity to a predicted rapid increase in the U.S. DT104 effective population size (circa 1996). When compared to DT104 genomes from other world regions ( n = 752 total genomes), several additional, sporadic artAB , Gifsy-1, and/or gogB loss events among clades encompassing ≤5 genomes were observed. In phenotypic assays that simulate conditions encountered during human and/or bovine digestion, members of the U.S. artAB -negative major clade did not differ from closely related Gifsy-1/ artAB / gogB -harboring U.S. DT104 strains (ANOVA raw P > 0.05); thus, future research is needed to elucidate the roles that artAB , gogB , and Gifsy-1 play in DT104 virulence in humans and animals. ### Competing Interest Statement The authors have declared no competing interest.