Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes

Author:

Beres Stephen B.1,Kachroo Priyanka1,Nasser Waleed1,Olsen Randall J.12,Zhu Luchang1,Flores Anthony R.13,de la Riva Ivan1,Paez-Mayorga Jesus1,Jimenez Francisco E.1,Cantu Concepcion1,Vuopio Jaana45,Jalava Jari5,Kristinsson Karl G.67,Gottfredsson Magnus67,Corander Jukka8,Fittipaldi Nahuel9,Di Luca Maria Chiara10,Petrelli Dezemona11,Vitali Luca A.10,Raiford Annessa12,Jenkins Leslie12,Musser James M.12

Affiliation:

1. Center 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

2. Departments of Pathology and Laboratory Medicine and Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA

3. Section of Infectious Diseases, Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, USA

4. Department of Medical Microbiology and Immunology, Medical Faculty, University of Turku, Turku, Finland

5. Department of Infectious Diseases, National Institute for Health and Welfare, Turku, Finland

6. Departments of Clinical Microbiology and Infectious Diseases, Landspitali University Hospital, Reykjavik, Iceland

7. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland

8. Department of Biostatistics, University of Oslo, Oslo, Norway, and Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland

9. Public Health Ontario, and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

10. School of Pharmacy, University of Camerino, Camerino, Italy

11. School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy

12. Comparative Medicine Program, Houston Methodist Research Institute, Houston, Texas, USA

Abstract

ABSTRACT For 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 emm 89 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. IMPORTANCE The 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.

Funder

Academy of Finland

The Fondren Foundation

Federation of European Microbiological Societies

European Society of Clinical Microbiology and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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