Evolution of the community-onset invasive Staphylococcus argenteus ST2250 clone in northeast Thailand is linked with the acquisition of livestock-associated staphylococcal genes

14 Jul 2017

$\textit{Staphylococcus argenteus}$ is a newly named species previously described as a divergent lineage of Staphylococcus aureus that has recently been shown to have a global distribution. Despite growing evidence of the clinical importance of this species, knowledge about its population epidemiology and genomic architecture is limited. We used whole-genome sequencing to evaluate and compare $\textit{S. aureus}$ (n 251) and $\textit{S. argenteus}$ (n 68) isolates from adults with staphylococcal sepsis at several hospitals in northeastern Thailand between 2006 and 2013. The majority (82%) of the $\textit{S. argenteus}$ isolates were of multilocus sequence type 2250 (ST2250). $\textit{S. aureus}$ was more diverse, although 43% of the isolates belonged to ST121. Bayesian analysis suggested an $\textit{S. argenteus}$ ST2250 substitution rate of 4.66 (95% confidence interval [CI], 3.12 to 6.38) mutations per genome per year, which was comparable to the $\textit{S. aureus}$ ST121 substitution rate of 4.07 (95% CI, 2.61 to 5.55). $\textit{S. argenteus}$ ST2250 emerged in Thailand an estimated 15 years ago, which contrasts with the $\textit{S. aureus}$ ST1, ST88, and ST121 clades that emerged around 100 to 150 years ago. Comparison of $\textit{S. argenteus}$ ST2250 genomes from Thailand and a global collection indicated a single introduction into Thailand, followed by transmission to local and more distant countries in Southeast Asia and further afield. $\textit{S. argenteus}$ and $\textit{S. aureus}$ shared around half of their core gene repertoire, indicating a high level of divergence and providing strong support for their classification as separate species. Several gene clusters were present in ST2250 isolates but absent from the other $\textit{S. argenteus}$ and $\textit{S. aureus}$ study isolates. These included multiple exotoxins and antibiotic resistance genes that have been linked previously with livestock-associated $\textit{S. aureus}$, consistent with a livestock reservoir for $\textit{S. argenteus}$. These genes appeared to be associated with plasmids and mobile genetic elements and may have contributed to the biological success of ST2250.