AUTHOR=Coates-Brown Rosanna , Moran Josephine C. , Pongchaikul Pisut , Darby Alistair C. , Horsburgh Malcolm J. 

TITLE=Comparative Genomics of Staphylococcus Reveals Determinants of Speciation and Diversification of Antimicrobial Defense

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02753

DOI=10.3389/fmicb.2018.02753

ISSN=1664-302X

ABSTRACT=<p>The bacterial genus <italic>Staphylococcus</italic> comprises diverse species with most being described as colonizers of human and animal skin. A relational analysis of features that discriminate its species and contribute to niche adaptation and survival remains to be fully described. In this study, an interspecies, whole-genome comparative analysis of 21 <italic>Staphylococcus</italic> species was performed based on their orthologues. Three well-defined multi-species groups were identified: group A (including <italic>aureus</italic>/<italic>epidermidis</italic>); group B (including <italic>saprophyticus</italic>/<italic>xylosus</italic>) and group C (including <italic>pseudintermedius</italic>/<italic>delphini</italic>). The machine learning algorithm Random Forest was applied to prioritize orthologs that drive formation of the <italic>Staphylococcus</italic> species groups A-C. Orthologues driving staphylococcal intrageneric diversity comprised regulatory, metabolic and antimicrobial resistance proteins. Notably, the BraSR (NsaRS) two-component system (TCS) and its associated BraDE transporters that regulate antimicrobial resistance showed limited distribution in the genus and their presence was most closely associated with a subset of <italic>Staphylococcus</italic> species dominated by those that colonize human skin. Divergence of BraSR and GraSR antimicrobial peptide survival TCS and their associated transporters was observed across the staphylococci, likely reflecting niche specific evolution of these TCS/transporters and their specificities for AMPs. Experimental evolution, with selection for resistance to the lantibiotic nisin, revealed multiple routes to resistance and differences in the selection outcomes of the BraSR-positive species <italic>S. hominis</italic> and <italic>S. aureus</italic>. Selection supported a role for GraSR in nisin survival responses of the BraSR-negative species <italic>S. saprophyticus</italic>. Our study reveals diversification of antimicrobial-sensing TCS across the staphylococci and hints at differential relationships between GraSR and BraSR in those species positive for both TCS.</p>