title: Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance.
abstract: Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Mark C
authors.initials: MC
authors.lastname: Enright
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Foster
authors.forename: Catrin E
authors.initials: CE
authors.lastname: Moore
authors.forename: Laurence
authors.initials: L
authors.lastname: Hurst
authors.forename: Rebecca
authors.initials: R
authors.lastname: Atkin
authors.forename: Andrew
authors.initials: A
authors.lastname: Barron
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bason
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Carol
authors.initials: C
authors.lastname: Chillingworth
authors.forename: Tracey
authors.initials: T
authors.lastname: Chillingworth
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Louise
authors.initials: L
authors.lastname: Clark
authors.forename: Craig
authors.initials: C
authors.lastname: Corton
authors.forename: Ann
authors.initials: A
authors.lastname: Cronin
authors.forename: Jon
authors.initials: J
authors.lastname: Doggett
authors.forename: Linda
authors.initials: L
authors.lastname: Dowd
authors.forename: Theresa
authors.initials: T
authors.lastname: Feltwell
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hance
authors.forename: Barbara
authors.initials: B
authors.lastname: Harris
authors.forename: Heidi
authors.initials: H
authors.lastname: Hauser
authors.forename: Simon
authors.initials: S
authors.lastname: Holroyd
authors.forename: Kay
authors.initials: K
authors.lastname: Jagels
authors.forename: Keith D
authors.initials: KD
authors.lastname: James
authors.forename: Nicola
authors.initials: N
authors.lastname: Lennard
authors.forename: Alexandra
authors.initials: A
authors.lastname: Line
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mayes
authors.forename: Sharon
authors.initials: S
authors.lastname: Moule
authors.forename: Karen
authors.initials: K
authors.lastname: Mungall
authors.forename: Douglas
authors.initials: D
authors.lastname: Ormond
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Ester
authors.initials: E
authors.lastname: Rabbinowitsch
authors.forename: Kim
authors.initials: K
authors.lastname: Rutherford
authors.forename: Mandy
authors.initials: M
authors.lastname: Sanders
authors.forename: Sarah
authors.initials: S
authors.lastname: Sharp
authors.forename: Mark
authors.initials: M
authors.lastname: Simmonds
authors.forename: Kim
authors.initials: K
authors.lastname: Stevens
authors.forename: Sally
authors.initials: S
authors.lastname: Whitehead
authors.forename: Bart G
authors.initials: BG
authors.lastname: Barrell
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
mesh_terms: D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics