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dc.contributor.authorBeres, Stephen B
dc.contributor.authorKachroo, Priyanka
dc.contributor.authorNasser, Waleed
dc.contributor.authorOlsen, Randall J
dc.contributor.authorZhu, Luchang
dc.contributor.authorFlores, Anthony R
dc.contributor.authorde la Riva, Ivan
dc.contributor.authorPaez-Mayorga, Jesus
dc.contributor.authorJimenez, Francisco E
dc.contributor.authorCantu, Concepcion
dc.contributor.authorVuopio, Jaana
dc.contributor.authorJalava, Jari
dc.contributor.authorKristinsson, Karl G
dc.contributor.authorGottfredsson, Magnus
dc.contributor.authorCorander, Jukka
dc.contributor.authorFittipaldi, Nahuel
dc.contributor.authorDi Luca, Maria Chiara
dc.contributor.authorPetrelli, Dezemona
dc.contributor.authorVitali, Luca A
dc.contributor.authorRaiford, Annessa
dc.contributor.authorJenkins, Leslie
dc.contributor.authorMusser, James M
dc.date.accessioned2016-08-24T16:01:07Z
dc.date.available2016-08-24T16:01:07Z
dc.date.issued2016
dc.date.submitted2016
dc.identifier.citationTranscriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes. 2016, 7 (3): MBioen
dc.identifier.issn2150-7511
dc.identifier.pmid27247229
dc.identifier.doi10.1128/mBio.00403-16
dc.identifier.urihttp://hdl.handle.net/2336/618747
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.en
dc.description.abstractFor over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects.
dc.description.abstractThe confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.
dc.description.sponsorshipFondren Foundation, Houston Methodist Hospital; the Academy of Finland (grant 255636); and the European Society of Clinical Microbiology and Infectious Diseases Training Fellowship 2011 and the Federation of European Societies of Microbiology Research Fellowship 2011-1 (awarded to M.C.D.L.)en
dc.language.isoenen
dc.publisherAmerican Society For Microbiologyen
dc.relation.urlhttp://dx.doi.org/ 10.1128/mBio.00403-16en
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895104/en
dc.rightsArchived with thanks to mBioen
dc.subjectFaraldsfræðien
dc.subjectSmitsjúkdómaren
dc.subjectBAC12
dc.subjectTMD12
dc.subject.meshTranscriptomeen
dc.subject.meshStreptococcus pyogenes/geneticsen
dc.subject.meshEpidemicsen
dc.subject.meshGenotypeen
dc.titleTranscriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes.en
dc.typeArticleen
dc.contributor.department1Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, and Houston Methodist Hospital, Houston, Texas, USA. 2Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, and Houston Methodist Hospital, Houston, Texas, USA Departments of Pathology and Laboratory Medicine and Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA. 3Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, and Houston Methodist Hospital, Houston, Texas, USA Section of Infectious Diseases, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA. 4Department of Medical Microbiology and Immunology, Medical Faculty, University of Turku, Turku, Finland Department of Infectious Diseases, National Institute for Health and Welfare, Turku, Finland. 5Department of Infectious Diseases, National Institute for Health and Welfare, Turku, Finland. 6Departments of Clinical Microbiology and Infectious Diseases, Landspitali University Hospital, Reykjavik, Iceland Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 7Department of Biostatistics, University of Oslo, Oslo, Norway, and Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. 8Public Health Ontario, and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 9School of Pharmacy, University of Camerino, Camerino, Italy. 10School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy. 11Comparative Medicine Program, Houston Methodist Research Institute, Houston, Texas, USA. 12Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, and Houston Methodist Hospital, Houston, Texas, USA Departments of Pathology and Laboratory Medicine and Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USAen
dc.identifier.journalmBioen
dc.rights.accessOpen Accessen
refterms.dateFOA2018-09-12T16:09:16Z
html.description.abstractFor over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects.
html.description.abstractThe confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.


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