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Title: Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance
Authors: Matthew T.G. Holden
Edward J. Feil
Jodi A. Lindsay
Sharon J. Peacock
Nicholas P.J. Day
Mark C. Enright
Tim J. Foster
Catrin E. Moore
Laurence Hurst
Rebecca Atkin
Andrew Barron
Nathalie Bason
Stephen D. Bentley
Carol Chillingworth
Tracey Chillingworth
Carol Churcher
Louise Clark
Craig Corton
Ann Cronin
Jon Doggett
Linda Dowd
Theresa Feltwell
Zahra Hance
Barbara Harris
Heidi Hauser
Simon Holroyd
Kay Jagels
Keith D. James
Nicola Lennard
Alexandra Line
Rebecca Mayes
Sharon Moule
Karen Mungall
Douglas Ormond
Michael A. Quail
Ester Rabbinowitsch
Kim Rutherford
Mandy Sanders
Sarah Sharp
Mark Simmonds
Kim Stevens
Sally Whitehead
Bart G. Barrell
Brian G. Spratt
Julian Parkhill
Wellcome Trust Sanger Institute
University of Bath
St George's University of London
Nuffield Department of Clinical Medicine
Trinity College Dublin
St Mary's Hospital London
Mahidol University
Keywords: Multidisciplinary
Issue Date: 29-Jun-2004
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.101, No.26 (2004), 9786-9791
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 ≈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: ≈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 SCC476), 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.
ISSN: 00278424
Appears in Collections:Scopus 2001-2005

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