Evolution of the <i>Staphylococcus argenteus</i> ST2250 Clone in Northeastern Thailand Is Linked with the Acquisition of Livestock-Associated Staphylococcal Genes

Abstract

<i>Staphylococcus argenteus</i> is a newly named species previously described as a divergent lineage of <i>Staphylococcus aureus</i> 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 <i>S. aureus</i> (<i>n</i> = 251) and <i>S. argenteus</i> (<i>n</i> = 68) isolates from adults with staphylococcal sepsis at several hospitals in northeastern Thailand between 2006 and 2013. The majority (82%) of the <i>S. argenteus</i> isolates were of multilocus sequence type 2250 (ST2250). <i>S. aureus</i> was more diverse, although 43% of the isolates belonged to ST121. Bayesian analysis suggested an <i>S. argenteus</i> 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 <i>S. aureus</i> ST121 substitution rate of 4.07 (95% CI, 2.61 to 5.55). <i>S. argenteus</i> ST2250 emerged in Thailand an estimated 15 years ago, which contrasts with the <i>S. aureus</i> ST1, ST88, and ST121 clades that emerged around 100 to 150 years ago. Comparison of <i>S. argenteus</i> 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. <i>S. argenteus</i> and <i>S. aureus</i> 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 <i>S. argenteus</i> and <i>S. aureus</i> study isolates. These included multiple exotoxins and antibiotic resistance genes that have been linked previously with livestock-associated <i>S. aureus</i>, consistent with a livestock reservoir for <i>S. argenteus</i> These genes appeared to be associated with plasmids and mobile genetic elements and may have contributed to the biological success of ST2250.<b>IMPORTANCE</b> In this study, we used whole-genome sequencing to understand the genome evolution and population structure of a systematic collection of ST2250 <i>S. argenteus</i> isolates. A newly identified ancestral species of <i>S. aureus</i>, <i>S. argenteus</i> has become increasingly known as a clinically important species that has been reported recently across various countries. Our results indicate that <i>S. argenteus</i> has spread at a relatively rapid pace over the past 2 decades across northeastern Thailand and acquired multiple exotoxin and antibiotic resistance genes that have been linked previously with livestock-associated <i>S. aureus</i> Our findings highlight the clinical importance and potential pathogenicity of <i>S. argenteus</i> as a recently emerging pathogen.