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.
Highlights
Staphylococcus aureus is one of the most common human pathogens and causes a wide range of infections, from skin and soft tissue infections (SSTIs) to life threatening diseases such as pneumonia, endocarditis, bacteremia and toxic-shock syndrome [1,2]
Global Population Structure We tested for sequence polymorphisms at 115 housekeeping loci of about 400 basepairs each (Table S1), in total covering about 1.7% (46,811 basepairs) of the genome from each of 154 S. aureus CC121 isolates
We identified 304 singlenucleotide polymorphisms, 5 insertions and 7 deletions ranging in size from 1 to 12 basepairs (Table S3)
Summary
Staphylococcus aureus is one of the most common human pathogens and causes a wide range of infections, from skin and soft tissue infections (SSTIs) to life threatening diseases such as pneumonia, endocarditis, bacteremia and toxic-shock syndrome [1,2]. A SNP-based, maximum-likelihood phylogenetic analysis revealed at least six major clades, A to F, within S. aureus CC121 (Figure 1).
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