title: Genetic structure of community acquired methicillin-resistant Staphylococcus aureus USA300.
abstract: BACKGROUND
  Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant bacterial pathogen that poses considerable clinical and public health challenges. The majority of the CA-MRSA disease burden consists of skin and soft tissue infections (SSTI) not associated with significant morbidity; however, CA-MRSA also causes severe, invasive infections resulting in significant morbidity and mortality. The broad range of disease severity may be influenced by bacterial genetic variation.
  
  
  RESULTS
  We sequenced the complete genomes of 36 CA-MRSA clinical isolates from the predominant North American community acquired clonal type USA300 (18 SSTI and 18 severe infection-associated isolates). While all 36 isolates shared remarkable genetic similarity, we found greater overall time-dependent sequence diversity among SSTI isolates. In addition, pathway analysis of non-synonymous variations revealed increased sequence diversity in the putative virulence genes of SSTI isolates.
  
  
  CONCLUSIONS
  Here we report the first whole genome survey of diverse clinical isolates of the USA300 lineage and describe the evolution of the pathogen over time within a defined geographic area. The results demonstrate the close relatedness of clinically independent CA-MRSA isolates, which carry implications for understanding CA-MRSA epidemiology and combating its spread.
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute, La Jolla, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Tewhey
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cannavino
authors.forename: John A D
authors.initials: JA
authors.lastname: Leake
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Ali
authors.initials: A
authors.lastname: Torkamani
authors.forename: John S
authors.initials: JS
authors.lastname: Bradley
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
mesh_terms: D001483:Base Sequence; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology*; D014644:Genetic Variation; D016680:Genome, Bacterial; D005838:Genotype; D060005:Genotyping Techniques; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D017720:Molecular Epidemiology; D009154:Mutation; D017422:Sequence Analysis, DNA; D018461:Soft Tissue Infections / Q000453:epidemiology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000453:epidemiology / Q000382:microbiology