RT Journal Article SR Electronic T1 Transcriptome remodeling contributes to epidemic disease caused by the human pathogen Streptococcus pyogenes JF bioRxiv FD Cold Spring Harbor Laboratory SP 043877 DO 10.1101/043877 A1 Stephen B. Beres A1 Priyanka Kachroo A1 Waleed Nasser A1 Randall J. Olsen A1 Luchang Zhu A1 Anthony R. Flores A1 Ivan de la Riva A1 Jesus Paez-Mayorga A1 Francisco E. Jimenez A1 Concepcion Cantu A1 Jaana Vuopio A1 Jari Jalava A1 Karl G. Kristinsson A1 Magnus Gottfredsson A1 Jukka Corander A1 Nahuel Fittipaldi A1 Maria Chiara Di Luca A1 Dezemona Petrelli A1 Luca A. Vitali A1 Annessa Raiford A1 Leslie Jenkins A1 James M. Musser YR 2016 UL http://biorxiv.org/content/early/2016/03/16/043877.abstract AB 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 1200 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 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.