Salmonella enterica serovar Typhimurium strains from passerines have caused wild bird deaths and human salmonellosis outbreaks in Europe, Oceania, and North America. Here, we performed comparative genomic analysis to explore the emergence, genetic relationship, and evolution of geographically dispersed passerine isolates. We found that passerine isolates from Europe and the United States clustered to form two lineages (EU and US passerine lineages), which were distinct from major S. Typhimurium lineages circulating in other diverse hosts (e.g., humans, cattle, pigs, chickens, and other avian hosts, such as pigeons and ducks). Further, passerine isolates from New Zealand clustered to form a sublineage (NZ passerine lineage) of the US passerine lineage. We inferred that the passerine isolates mutated at a rate of 3.2 × 10-7 substitutions/site/year, and the US, EU, and NZ passerine lineages emerged in approximately 1952, 1970, and 1996, respectively. Isolates from the three lineages presented genetic similarity, such as lack of antimicrobial resistance genes and accumulation of the same virulence pseudogenes. In addition, genetic diversity due to microevolution existed in the three passerine lineages. Specifically, pseudogenization in the type 1 fimbrial gene fimC (deletion of G at position 87) was detected only in the US and NZ passerine isolates, while single-base deletions in type 3 secretion system effector genes (i.e., gogB, sseJ, and sseK2) cooccurred solely in the EU passerine isolates. These findings provide insights into the evolution, host adaptation, and epidemiology of S. Typhimurium in passerines. IMPORTANCE Passerine-associated S. Typhimurium strains have been linked to human salmonellosis outbreaks in recent years. Here, we investigated the phylogenetic relationship of globally distributed passerine isolates and profiled their genomic similarity and diversity. Our study reveals two passerine-associated S. Typhimurium lineages circulating in Europe, Oceania, and North America. Isolates from the two lineages presented phylogenetic and genetic signatures that were distinct from those of isolates from other hosts. The findings shed light on the host adaptation of S. Typhimurium in passerines and are important for source attribution of S. Typhimurium strains to avian hosts. Further, we found that S. Typhimurium definitive phage type 160 (DT160) from passerines, which caused decades-long human salmonellosis outbreaks in New Zealand and Australia, formed a sublineage of the US passerine lineage, suggesting that DT160 might have originated from passerines outside Oceania. Our study demonstrates the importance of whole-genome sequencing and genomic analysis of historical microbial collections to modern epidemiologic surveillance.
Keywords: Salmonella enterica serovar Typhimurium; comparative genomic analysis; host adaptation; outbreak; passerine.