A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic

Matthew T G Holden; Li-Yang Hsu; Kevin Kurt; Lucy A Weinert; Alison E Mather; Simon R Harris; Birgit Strommenger; Franziska Layer; Wolfgang Witte; Herminia de Lencastre; Robert Skov; Henrik Westh; Helena Zemlickova; Geoffrey Coombs; Angela M Kearns; Robert L R Hill; Jonathan Edgeworth; Ian Gould; Vanya Gant; Jonathan Cooke; Giles F Edwards; Paul McAdam; Kate E Templeton; Angela McCann; Zhemin Zhou; Santiago Castillo-Ramirez; Edward J Feil; Lyndsey O Hudson; Mark C Enright; Francois Balloux; David M Aanensen; Brian G Spratt; J Ross Fitzgerald; Julian Parkhill; Mark Achtman; Stephen D Bentley; Ulrich Nübel

doi:10.1101/gr.147710.112

A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic

Matthew T G Holden, Li-Yang Hsu, Kevin Kurt, Lucy A Weinert, Alison E Mather, Simon R Harris, Birgit Strommenger, Franziska Layer, Wolfgang Witte, Herminia de Lencastre, Robert Skov, Henrik Westh, Helena Zemlickova, Geoffrey Coombs, Angela M Kearns, Robert L R Hill, Jonathan Edgeworth, Ian Gould, Vanya Gant, Jonathan CookeGiles F Edwards, Paul McAdam, Kate E Templeton, Angela McCann, Zhemin Zhou, Santiago Castillo-Ramirez, Edward J Feil, Lyndsey O Hudson, Mark C Enright, Francois Balloux, David M Aanensen, Brian G Spratt, J Ross Fitzgerald, Julian Parkhill, Mark Achtman, Stephen D Bentley, Ulrich Nübel

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

Abstract

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalised patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with healthcare. The most rapidly spreading and tenacious healthcare-associated clone in Europe currently is EMRSA-15, a lineage that was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. To understand the genetic events that have accompanied the emergence of the EMRSA-15 pandemic, we obtained genome sequences for 193 isolates that were chosen for their geographical and temporal diversity, and belong to the same multilocus sequence type as EMRSA-15. Using phylogenomic methods, we were able to show that the current pandemic population of EMRSA-15 descends from a healthcare-associated MRSA epidemic that spread through England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 sub-clone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this sub-clone over the last twenty years has grown four times faster than its progenitor. Using comparative genomic analysis we were able to identify the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.

Original language	English
Pages (from-to)	653-664
Journal	Genome Research
Volume	23
Issue number	4
Early online date	8 Jan 2013
DOIs	https://doi.org/10.1101/gr.147710.112
Publication status	Published - Apr 2013

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10.1101/gr.147710.112

A genomic portrait of the emergence, evolution and global spread of a methicillin resistant Staphylococcus aureus pandemic
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/
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http://genome.cshlp.org/content/23/4/653

Future-Proofing the sustainability of the MRC high throughput sequencing hub in Scotland
Blaxter, M. (Principal Investigator)
MRC
1/10/12 → 30/09/14
Project: Research
Ark Genomics
Watson, M. (Principal Investigator), Archibald, A. (Co-investigator) & Burt, D. (Co-investigator)
Biotechnology and Biological Sciences Research Council
1/04/12 → 31/03/17
Project: Research
Innate immunity and endemic diseases in livestock species
Collie, D. (Principal Investigator), Beard, P. (Co-investigator), Bishop, S. (Co-investigator), Bronsvoort, M. (Co-investigator), Burt, D. (Co-investigator), Fitzgerald, R. (Co-investigator), Freeman, T. (Co-investigator), Gally, D. (Co-investigator), Gill, A. (Co-investigator), Glass, E. (Co-investigator), Hocking, P. (Co-investigator), Hope, J. (Co-investigator), Hume, D. (Co-investigator), Kaiser, P. (Co-investigator), Mabbott, N. (Co-investigator), McLachlan, G. (Co-investigator), Morrison, L. (Co-investigator), Stevens, J. (Co-investigator), Stevens, M. (Co-investigator) & Watson, M. (Co-investigator)
Biotechnology and Biological Sciences Research Council
1/04/12 → 31/03/17
Project: Research

Cite this

Holden, M. T. G., Hsu, L.-Y., Kurt, K., Weinert, L. A., Mather, A. E., Harris, S. R., Strommenger, B., Layer, F., Witte, W., de Lencastre, H., Skov, R., Westh, H., Zemlickova, H., Coombs, G., Kearns, A. M., Hill, R. L. R., Edgeworth, J., Gould, I., Gant, V., ... Nübel, U. (2013). A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic. Genome Research, 23(4), 653-664. https://doi.org/10.1101/gr.147710.112

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title = "A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic",

abstract = "The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalised patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with healthcare. The most rapidly spreading and tenacious healthcare-associated clone in Europe currently is EMRSA-15, a lineage that was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. To understand the genetic events that have accompanied the emergence of the EMRSA-15 pandemic, we obtained genome sequences for 193 isolates that were chosen for their geographical and temporal diversity, and belong to the same multilocus sequence type as EMRSA-15. Using phylogenomic methods, we were able to show that the current pandemic population of EMRSA-15 descends from a healthcare-associated MRSA epidemic that spread through England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 sub-clone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this sub-clone over the last twenty years has grown four times faster than its progenitor. Using comparative genomic analysis we were able to identify the molecular genetic basis of 99.8\% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.",

author = "Holden, \{Matthew T G\} and Li-Yang Hsu and Kevin Kurt and Weinert, \{Lucy A\} and Mather, \{Alison E\} and Harris, \{Simon R\} and Birgit Strommenger and Franziska Layer and Wolfgang Witte and \{de Lencastre\}, Herminia and Robert Skov and Henrik Westh and Helena Zemlickova and Geoffrey Coombs and Kearns, \{Angela M\} and Hill, \{Robert L R\} and Jonathan Edgeworth and Ian Gould and Vanya Gant and Jonathan Cooke and Edwards, \{Giles F\} and Paul McAdam and Templeton, \{Kate E\} and Angela McCann and Zhemin Zhou and Santiago Castillo-Ramirez and Feil, \{Edward J\} and Hudson, \{Lyndsey O\} and Enright, \{Mark C\} and Francois Balloux and Aanensen, \{David M\} and Spratt, \{Brian G\} and Fitzgerald, \{J Ross\} and Julian Parkhill and Mark Achtman and Bentley, \{Stephen D\} and Ulrich N{\"u}bel",

note = "J.R.F., G.F.E., and K.E.T. were supported by a grant from the Chief Scientists Office Scotland and by aMedical Research Council doctoral training grant (for PRM), and by the BBSRC ( JRF).",

year = "2013",

month = apr,

doi = "10.1101/gr.147710.112",

language = "English",

volume = "23",

pages = "653--664",

journal = "Genome Research",

issn = "1549-5469",

publisher = "Cold Spring Harbor Laboratory Press",

number = "4",

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Holden, MTG, Hsu, L-Y, Kurt, K, Weinert, LA, Mather, AE, Harris, SR, Strommenger, B, Layer, F, Witte, W, de Lencastre, H, Skov, R, Westh, H, Zemlickova, H, Coombs, G, Kearns, AM, Hill, RLR, Edgeworth, J, Gould, I, Gant, V, Cooke, J, Edwards, GF, McAdam, P, Templeton, KE, McCann, A, Zhou, Z, Castillo-Ramirez, S, Feil, EJ, Hudson, LO, Enright, MC, Balloux, F, Aanensen, DM, Spratt, BG, Fitzgerald, JR, Parkhill, J, Achtman, M, Bentley, SD & Nübel, U 2013, 'A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic', Genome Research, vol. 23, no. 4, pp. 653-664. https://doi.org/10.1101/gr.147710.112

TY - JOUR

T1 - A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic

AU - Holden, Matthew T G

AU - Hsu, Li-Yang

AU - Kurt, Kevin

AU - Weinert, Lucy A

AU - Mather, Alison E

AU - Harris, Simon R

AU - Strommenger, Birgit

AU - Layer, Franziska

AU - Witte, Wolfgang

AU - de Lencastre, Herminia

AU - Skov, Robert

AU - Westh, Henrik

AU - Zemlickova, Helena

AU - Coombs, Geoffrey

AU - Kearns, Angela M

AU - Hill, Robert L R

AU - Edgeworth, Jonathan

AU - Gould, Ian

AU - Gant, Vanya

AU - Cooke, Jonathan

AU - Edwards, Giles F

AU - McAdam, Paul

AU - Templeton, Kate E

AU - McCann, Angela

AU - Zhou, Zhemin

AU - Castillo-Ramirez, Santiago

AU - Feil, Edward J

AU - Hudson, Lyndsey O

AU - Enright, Mark C

AU - Balloux, Francois

AU - Aanensen, David M

AU - Spratt, Brian G

AU - Fitzgerald, J Ross

AU - Parkhill, Julian

AU - Achtman, Mark

AU - Bentley, Stephen D

AU - Nübel, Ulrich

N1 - J.R.F., G.F.E., and K.E.T. were supported by a grant from the Chief Scientists Office Scotland and by aMedical Research Council doctoral training grant (for PRM), and by the BBSRC ( JRF).

PY - 2013/4

Y1 - 2013/4

N2 - The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalised patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with healthcare. The most rapidly spreading and tenacious healthcare-associated clone in Europe currently is EMRSA-15, a lineage that was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. To understand the genetic events that have accompanied the emergence of the EMRSA-15 pandemic, we obtained genome sequences for 193 isolates that were chosen for their geographical and temporal diversity, and belong to the same multilocus sequence type as EMRSA-15. Using phylogenomic methods, we were able to show that the current pandemic population of EMRSA-15 descends from a healthcare-associated MRSA epidemic that spread through England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 sub-clone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this sub-clone over the last twenty years has grown four times faster than its progenitor. Using comparative genomic analysis we were able to identify the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.

AB - The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalised patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with healthcare. The most rapidly spreading and tenacious healthcare-associated clone in Europe currently is EMRSA-15, a lineage that was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. To understand the genetic events that have accompanied the emergence of the EMRSA-15 pandemic, we obtained genome sequences for 193 isolates that were chosen for their geographical and temporal diversity, and belong to the same multilocus sequence type as EMRSA-15. Using phylogenomic methods, we were able to show that the current pandemic population of EMRSA-15 descends from a healthcare-associated MRSA epidemic that spread through England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 sub-clone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this sub-clone over the last twenty years has grown four times faster than its progenitor. Using comparative genomic analysis we were able to identify the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.

U2 - 10.1101/gr.147710.112

DO - 10.1101/gr.147710.112

M3 - Article

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SN - 1549-5469

VL - 23

SP - 653

EP - 664

JO - Genome Research

JF - Genome Research

IS - 4

ER -

A genomic portrait of the emergence, evolution, and global spread of a methicillin resistant Staphylococcus aureus pandemic

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Projects

Future-Proofing the sustainability of the MRC high throughput sequencing hub in Scotland

Ark Genomics

Innate immunity and endemic diseases in livestock species

Cite this