HI1 and I1 Resistance Plasmids from Salmonella enterica Serovar Typhimurium Strain SRC27 Are Epidemic

Conjugative plasmids are a major contributor to the global spread of antibiotic resistance determinants, but the tracking of their evolutionary history is often neglected. Salmonella enterica serovar Typhimurium (S. Typhimurium) strain SRC27 was isolated from an equine infection in Australia in 1999. SRC27 was known to carry conjugative HI1 and I1 resistance plasmids. In this study, SRC27 was sequenced to determine the relationship between these HI1 and I1 resistance plasmids it was known to carry and HI1 and I1 resistance plasmids circulating worldwide. The resistance genes in the HI1 plasmid, pSRC27-H, are all located in a single complex 34.7 kb resistance region. The backbone sequence and location of the pSRC27-H resistance island were used to identify the most closely related HI1 plasmids among the >90 that have been sequenced since 2011. This defined a sublineage of 20 type 2 HI1 plasmids that have been circulating in Europe, Asia, North America, and Australia since at least 1993. The overall resistance gene content of these HI1 plasmids differs, indicating extensive evolution in situ through the acquisition of additional transposons and deletion or replacement of ancestral regions. The I1 plasmid contains a complete copy of Tn5393a, containing the strAB genes that confer resistance to streptomycin. The precise location of Tn5393a in the backbone also defined a globally disseminated sublineage of I1 plasmids, many of which have also acquired additional resistance determinants. The sequence revealed that SRC27 also carried two additional plasmids, the pSLT-type FIB(S):FII(S) virulence plasmid and a small cryptic theta-replicating Col156 plasmid.