Evolution and Diversity of the Antimicrobial Resistance Associated Mobilome in : A Probable Mobile Genetic Elements Reservoir for Other Streptococci.

is a previously neglected, newly emerging multidrug-resistant zoonotic pathogen. Mobile genetic elements (MGEs) play a key role in intra- and interspecies horizontal transfer of antimicrobial resistance (AMR) determinants. Although, previous studies showed the presence of several MGEs, a comprehensive analysis of AMR-associated mobilome as well as their interaction and evolution has not been performed. In this study, we presented the AMR-associated mobilome and their insertion hotspots in . Integrative conjugative elements (ICEs), prophages and tandem MGEs were located at different insertion sites, while 86% of the AMR-associated MGEs were inserted at and loci. Comprehensive analysis of insertions at and loci among four pathogenic species (, and ) revealed the existence of different groups of MGEs, including Tn5252, ICE1108, and TnGBS2 groups ICEs, Φm46.1 group prophage, ICE_ICE and ICE_prophage tandem MGEs. Comparative ICE genomics of ICE2603 family revealed that module exchange and acquisition/deletion were the main mechanisms in MGEs' expansion and evolution. Furthermore, the observation of tandem MGEs reflected a novel mechanism for MGE diversity. Moreover, an competition assay showed no visible fitness cost was observed between different MGE-carrying isolates and a conjugation assay revealed the transferability of ICE2603 family of ICEs. Our statistics further indicated that the prevalence and diversity of MGEs in is much greater than in other three species which prompted our hypothesis that is probably a MGEs reservoir for other streptococci. In conclusion, our results showed that acquisition of MGEs confers not only its capability as a multidrug resistance pathogen, but also represents a paradigm to study the modular evolution and matryoshkas of MGEs.