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

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Authors
Beres, Stephen B
Kachroo, Priyanka
Nasser, Waleed
Olsen, Randall J
Zhu, Luchang
Flores, Anthony R
de la Riva, Ivan
Paez-Mayorga, Jesus
Jimenez, Francisco E
Cantu, Concepcion
Vuopio, Jaana
Jalava, Jari
Kristinsson, Karl G
Gottfredsson, Magnus
Corander, Jukka
Fittipaldi, Nahuel
Di Luca, Maria Chiara
Petrelli, Dezemona
Vitali, Luca A
Raiford, Annessa
Jenkins, Leslie
Musser, James M
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2016

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Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes. 2016, 7 (3): MBio
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 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.
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.
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To 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.
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http://dx.doi.org/ 10.1128/mBio.00403-16
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895104/
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ae974a485f413a2113503eed53cd6c53
10.1128/mBio.00403-16
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