Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance

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

doi:10.1073/pnas.0402521101

Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance

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 DoggettLinda 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^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	9786-9791
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	26
DOIs	https://doi.org/10.1073/pnas.0402521101
Publication status	Published - 29 Jun 2004
Externally published	Yes

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10.1073/pnas.0402521101

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Holden, M. T. G., Feil, E. J., Lindsay, J. A., Peacock, S. J., Day, N. P. J., Enright, M. C., Foster, T. J., Moore, C. E., Hurst, L., Atkin, R., Barron, A., Bason, N., Bentley, S. D., Chillingworth, C., Chillingworth, T., Churcher, C., Clark, L., Corton, C., Cronin, A., ... Parkhill, J. (2004). Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance. Proceedings of the National Academy of Sciences of the United States of America, 101(26), 9786-9791. https://doi.org/10.1073/pnas.0402521101

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title = "Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the 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 ≈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.",

author = "Holden, {Matthew T.G.} and Feil, {Edward J.} and Lindsay, {Jodi A.} and Peacock, {Sharon J.} and Day, {Nicholas P.J.} and Enright, {Mark C.} and Foster, {Tim J.} and Moore, {Catrin E.} and Laurence Hurst and Rebecca Atkin and Andrew Barron and Nathalie Bason and Bentley, {Stephen D.} and Carol Chillingworth and Tracey Chillingworth and Carol Churcher and Louise Clark and Craig Corton and Ann Cronin and Jon Doggett and Linda Dowd and Theresa Feltwell and Zahra Hance and Barbara Harris and Heidi Hauser and Simon Holroyd and Kay Jagels and James, {Keith D.} and Nicola Lennard and Alexandra Line and Rebecca Mayes and Sharon Moule and Karen Mungall and Douglas Ormond and Quail, {Michael A.} and Ester Rabbinowitsch and Kim Rutherford and Mandy Sanders and Sarah Sharp and Mark Simmonds and Kim Stevens and Sally Whitehead and Barrell, {Bart G.} and Spratt, {Brian G.} and Julian Parkhill",

year = "2004",

month = jun,

day = "29",

doi = "10.1073/pnas.0402521101",

language = "English",

volume = "101",

pages = "9786--9791",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "26",

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Holden, MTG, Feil, EJ, Lindsay, JA, Peacock, SJ, Day, NPJ, Enright, MC, Foster, TJ, Moore, CE, Hurst, L, Atkin, R, Barron, A, Bason, N, Bentley, SD, Chillingworth, C, Chillingworth, T, Churcher, C, Clark, L, Corton, C, Cronin, A, Doggett, J, Dowd, L, Feltwell, T, Hance, Z, Harris, B, Hauser, H, Holroyd, S, Jagels, K, James, KD, Lennard, N, Line, A, Mayes, R, Moule, S, Mungall, K, Ormond, D, Quail, MA, Rabbinowitsch, E, Rutherford, K, Sanders, M, Sharp, S, Simmonds, M, Stevens, K, Whitehead, S, Barrell, BG, Spratt, BG & Parkhill, J 2004, 'Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 26, pp. 9786-9791. https://doi.org/10.1073/pnas.0402521101

Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance. / Holden, Matthew T.G.; Feil, Edward J.; Lindsay, Jodi A. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 26, 29.06.2004, p. 9786-9791.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Complete genomes of two clinical Staphylococcus aureus strains

T2 - Evidence for the evolution of virulence and drug resistance

AU - Holden, Matthew T.G.

AU - Feil, Edward J.

AU - Lindsay, Jodi A.

AU - Peacock, Sharon J.

AU - Day, Nicholas P.J.

AU - Enright, Mark C.

AU - Foster, Tim J.

AU - Moore, Catrin E.

AU - Hurst, Laurence

AU - Atkin, Rebecca

AU - Barron, Andrew

AU - Bason, Nathalie

AU - Bentley, Stephen D.

AU - Chillingworth, Carol

AU - Chillingworth, Tracey

AU - Churcher, Carol

AU - Clark, Louise

AU - Corton, Craig

AU - Cronin, Ann

AU - Doggett, Jon

AU - Dowd, Linda

AU - Feltwell, Theresa

AU - Hance, Zahra

AU - Harris, Barbara

AU - Hauser, Heidi

AU - Holroyd, Simon

AU - Jagels, Kay

AU - James, Keith D.

AU - Lennard, Nicola

AU - Line, Alexandra

AU - Mayes, Rebecca

AU - Moule, Sharon

AU - Mungall, Karen

AU - Ormond, Douglas

AU - Quail, Michael A.

AU - Rabbinowitsch, Ester

AU - Rutherford, Kim

AU - Sanders, Mandy

AU - Sharp, Sarah

AU - Simmonds, Mark

AU - Stevens, Kim

AU - Whitehead, Sally

AU - Barrell, Bart G.

AU - Spratt, Brian G.

AU - Parkhill, Julian

PY - 2004/6/29

Y1 - 2004/6/29

N2 - 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.

AB - 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.

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 26

ER -

Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance

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