title: Subpopulations of Staphylococcus aureus clonal complex 121 are associated with distinct clinical entities.
abstract: We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F) within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis) clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC). In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia) were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region.
authors.affiliation: Robert Koch Institute, Wernigerode, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kurt
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.forename: Frederic
authors.initials: F
authors.lastname: Laurent
authors.forename: Richard V
authors.initials: RV
authors.lastname: Goering
authors.forename: Helena
authors.initials: H
authors.lastname: Žemličková
authors.forename: Ivana
authors.initials: I
authors.lastname: Machova
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Struelens
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Zautner
authors.forename: Silva
authors.initials: S
authors.lastname: Holtfreter
authors.forename: Barbara
authors.initials: B
authors.lastname: Bröker
authors.forename: Stephen
authors.initials: S
authors.lastname: Ritchie
authors.forename: Sin
authors.initials: S
authors.lastname: Reaksmey
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Christiane
authors.initials: C
authors.lastname: Cuny
authors.forename: Franziska
authors.initials: F
authors.lastname: Layer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witte
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nübel
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics; D020043:Genes, Essential; D016680:Genome, Bacterial; D006801:Humans; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification* / Q000235:genetics*
chemical_list: D001427:Bacterial Toxins