title: Pan-genomic perspective on the evolution of theStaphylococcus aureusUSA300 epidemic.
abstract: Staphylococcus aureusUSA300 represents the dominant community-associated methicillin-resistantS. aureuslineage in the USA, where it is a major cause of skin and soft tissue infections. Previous comparative genomic studies have described the population structure and evolution of USA300 based on geographically restricted isolate collections. Here, we investigated the USA300 population by sequencing genomes of a geographically distributed panel of 191 clinicalS. aureusisolates belonging to clonal complex 8 (CC8), derived from the Tigecycline Evaluation and Surveillance Trial program. Isolates were collected at 12 healthcare centres across nine USA states in 2004, 2009 or 2010. Reconstruction of evolutionary relationships revealed that CC8 was dominated by USA300 isolates (154/191, 81 %), which were heterogeneous and demonstrated limited phylogeographic clustering. Analysis of the USA300 core genomes revealed an increase in median pairwise SNP distance from 62 to 98 between 2004 and 2010, with a stable pattern of above average dN/dSratios. The phylogeny of the USA300 population indicated that early diversification events led to the formation of nested clades, which arose through cumulative acquisition of predominantly non-synonymous SNPs in various coding sequences. The accessory genome of USA300 was largely homogenous and consisted of elements previously associated with this lineage. We observed an emergence of SCCmecnegative and ACME negative USA300 isolates amongst more recent samples, and an increase in the prevalence of ϕSa5 prophage. Together, the analysedS. aureusUSA300 collection revealed an evolving pan-genome through increased core genome heterogeneity and temporal variation in the frequency of certain accessory elements.
authors.affiliation: 1​The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Jamrozy
authors.affiliation: 1​The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: 2​Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors.forename: Naglaa
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: 1​The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.|3​London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: 2​Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Tan
authors.affiliation: 1​The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: 2​Pfizer Vaccine Research and Development, Pearl River, New York, USA.
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.affiliation: 4​School of Medicine, University of St Andrews, St Andrews, Fife KY16 9TF, UK.
authors.forename: Matthew T G
authors.initials: MTG
authors.lastname: Holden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000453:epidemiology* / Q000382:microbiology*; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D007223:Infant; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D010802:Phylogeny; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D014481:United States / Q000453:epidemiology; D000073336:Whole Genome Sequencing; D055815:Young Adult
keywords: Evolution; MRSA; USA300