AUTHOR=Mcgavin Martin J., Arsic Benjamin , Nickerson Nicholas N.

TITLE=Evolutionary blueprint for host- and niche-adaptation in Staphylococcus aureus clonal complex CC30

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=2

YEAR=2012

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2012.00048

DOI=10.3389/fcimb.2012.00048

ISSN=2235-2988

ABSTRACT=<p><italic>Staphylococcus aureus</italic> clonal complex CC30 has caused infectious epidemics for more than 60 years, and, therefore, provides a model system to evaluate how evolution has influenced the disease potential of closely related strains. In previous multiple genome comparisons, phylogenetic analyses established three major branches that evolved from a common ancestor. Clade 1, comprised of historic pandemic phage type 80/81 methicillin susceptible <italic>S. aureus</italic> (MSSA), and Clade 2 comprised of contemporary community acquired methicillin resistant <italic>S. aureus</italic> (CA-MRSA) were hyper-virulent in murine infection models. Conversely, Clade 3 strains comprised of contemporary hospital associated MRSA (HA-MRSA) and clinical MSSA exhibited attenuated virulence, due to common single nucleotide polymorphisms (SNP's) that abrogate production of α-hemolysin Hla, and interfere with signaling of the accessory gene regulator <italic>agr</italic>. We have now completed additional <italic>in silico</italic> genome comparisons of 15 additional CC30 genomes in the public domain, to assess the hypothesis that Clade 3 has evolved to favor niche adaptation. In addition to SNP's that influence <italic>agr</italic> and <italic>hla</italic>, other common traits of Clade 3 include tryptophan auxotrophy due to a di-nucleotide deletion within <italic>trpD</italic>, a premature stop codon within <italic>isdH</italic> encoding an immunogenic cell surface protein involved in iron acquisition, loss of a genomic toxin–antitoxin (TA) addiction module, acquisition of <italic>S. aureus</italic> pathogenicity islands SaPI4, and SaPI2 encoding toxic shock syndrome toxin <italic>tst</italic>, and increased copy number of insertion sequence ISSau2, which appears to target transcription terminators. Compared to other Clade 3 MSSA, <italic>S. aureus</italic> MN8, which is associated with Staphylococcal toxic shock syndrome, exhibited a unique ISSau2 insertion, and enhanced production of toxic shock syndrome toxin encoded by SaPI2. Cumulatively, our data support the notion that Clade 3 strains are following an evolutionary blueprint toward niche-adaptation.</p>