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doi:10.1016/j.epidem.2011.07.001
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Evolution of diversity in epidemics revealed by analysis of the human bacterial pathogen group A Streptococcus
Ronan K. Carroll<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>, Stephen B. Beres<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>, Izabela Sitkiewicz<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP><SUP>, </SUP><SUP>e</SUP>, Leif Peterson<SUP>b</SUP>, Ris? K. Matsunami<SUP>c</SUP>, David A. Engler<SUP>c</SUP>, Anthony R. Flores<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP><SUP>, </SUP><SUP>f</SUP>, Paul Sumby<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP> and James M. Musser<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>
<SUP>a</SUP> Center for Molecular and Translational Human Infectious Diseases Research, <SUP>b</SUP> Center for Biostatistics, <SUP>c</SUP> Proteomics Laboratory, The Methodist Hospital Research Institute, <SUP>d</SUP> Department of Pathology and Genomic Medicine, The Methodist Hospital System, 6565 Fannin Street, Houston, TX 77030, USA, <SUP>e</SUP> Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00/725 Warsaw, Poland, <SUP>f</SUP> Section of Infectious Diseases, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA
Received 15 March 2011; revised 21 June 2011; accepted 4 July 2011. Available online 5 August 2011.
Abstract
Advancements in high-throughput, high-volume data generating techniques increasingly present us with opportunities to probe new areas of biology. In this work we assessed the extent to which four closely related and genetically representative strains of group A Streptococcus causing epidemic disease have differentiated from one another. Comparative genome sequencing, expression microarray analysis, and proteomic studies were used in parallel to assess strain variation. The extent of phenotypic differentiation was unexpectedly large. We found significant associations between genetic polymorphisms and alterations in gene expression allowing us to estimate the frequency with which specific types of polymorphisms alter gene transcription. We identified polymorphisms in the gene (ropB) encoding the RopB regulator that associate with altered transcription of speB and production of the SpeB protein, a critical secreted protease virulence factor. Although these four epidemic strains are closely related, a key discovery is that accumulation of modest genetic changes has rapidly resulted in significant strain phenotypic differentiation, including the extracellular proteome that contains multiple virulence factors. These data provide enhanced understanding of genetic events resulting in strain variation in bacterial epidemics.
Keywords: M3; transcriptome; epidemic; ropB; rgg; speB
Corresponding author. Tel.: +1 713 441 5890; fax: +1 713 441 3447.
Note to users: The section "Articles in Press" contains peer reviewed accepted articles to be published in this journal. When the final article is assigned to an issue of the journal, the "Article in Press" version will be removed from this section and will appear in the associated published journal issue. The date it was first made available online will be carried over. Please be aware that although "Articles in Press" do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and the use of punctuation.
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doi:10.1016/j.epidem.2011.07.001
Permissions & Reprints
Evolution of diversity in epidemics revealed by analysis of the human bacterial pathogen group A Streptococcus
Ronan K. Carroll<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>, Stephen B. Beres<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>, Izabela Sitkiewicz<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP><SUP>, </SUP><SUP>e</SUP>, Leif Peterson<SUP>b</SUP>, Ris? K. Matsunami<SUP>c</SUP>, David A. Engler<SUP>c</SUP>, Anthony R. Flores<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP><SUP>, </SUP><SUP>f</SUP>, Paul Sumby<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP> and James M. Musser<SUP>a</SUP><SUP>, </SUP><SUP>d</SUP>
<SUP>a</SUP> Center for Molecular and Translational Human Infectious Diseases Research, <SUP>b</SUP> Center for Biostatistics, <SUP>c</SUP> Proteomics Laboratory, The Methodist Hospital Research Institute, <SUP>d</SUP> Department of Pathology and Genomic Medicine, The Methodist Hospital System, 6565 Fannin Street, Houston, TX 77030, USA, <SUP>e</SUP> Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00/725 Warsaw, Poland, <SUP>f</SUP> Section of Infectious Diseases, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA
Received 15 March 2011; revised 21 June 2011; accepted 4 July 2011. Available online 5 August 2011.
Abstract
Advancements in high-throughput, high-volume data generating techniques increasingly present us with opportunities to probe new areas of biology. In this work we assessed the extent to which four closely related and genetically representative strains of group A Streptococcus causing epidemic disease have differentiated from one another. Comparative genome sequencing, expression microarray analysis, and proteomic studies were used in parallel to assess strain variation. The extent of phenotypic differentiation was unexpectedly large. We found significant associations between genetic polymorphisms and alterations in gene expression allowing us to estimate the frequency with which specific types of polymorphisms alter gene transcription. We identified polymorphisms in the gene (ropB) encoding the RopB regulator that associate with altered transcription of speB and production of the SpeB protein, a critical secreted protease virulence factor. Although these four epidemic strains are closely related, a key discovery is that accumulation of modest genetic changes has rapidly resulted in significant strain phenotypic differentiation, including the extracellular proteome that contains multiple virulence factors. These data provide enhanced understanding of genetic events resulting in strain variation in bacterial epidemics.
Keywords: M3; transcriptome; epidemic; ropB; rgg; speB
Corresponding author. Tel.: +1 713 441 5890; fax: +1 713 441 3447.
Note to users: The section "Articles in Press" contains peer reviewed accepted articles to be published in this journal. When the final article is assigned to an issue of the journal, the "Article in Press" version will be removed from this section and will appear in the associated published journal issue. The date it was first made available online will be carried over. Please be aware that although "Articles in Press" do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and the use of punctuation.
There are three types of "Articles in Press":
- Accepted manuscripts: these are articles that have been peer reviewed and accepted for publication by the Editorial Board. The articles have not yet been copy edited and/or formatted in the journal house style.
- Uncorrected proofs: these are copy edited and formatted articles that are not yet finalized and that will be corrected by the authors. Therefore the text could change before final publication.
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