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
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.
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 Departments of Pathology and Laboratory Medicine and Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
mBio. 2016 May 31;7(3):e00403-16. doi: 10.1128/mBio.00403-16.
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.
一个多世纪以来，感染生物学研究的一个基本目标是了解导致流行病起源和持续存在的分子过程。关于环境事件或病原体进化在这些过程中占主导地位的程度，出现了不同的假设。然而，针对这一重要问题的研究却少之又少。基于对1200株化脓性链球菌emm89型感染分离株的群体病原体基因组分析，我们报告了一系列水平基因转移事件产生了一种新的致病基因型，其感染能力增强，导致至少在两大洲出现了疾病流行浪潮。总体而言，这些和其他基因变化极大地重塑了进化后代的转录组，导致毒力基因广泛差异表达，并改变了病原体与宿主的相互作用，包括增强了免疫逃避能力。我们的研究结果描绘了发生的精确分子遗传变化，并增进了我们对有助于在流行中取得成功的病原体克隆出现和持续存在的进化过程的理解。这些数据对于理解细菌流行病以及为减轻其有害影响的转化研究工作具有重要意义。
对病原体菌株出现背后的分子事件、介导毒力改变的进化遗传过程以及流行病的综合研究尚处于起步阶段。尽管了解这些事件对于制定新的或改进的健康保护策略是必要的，但令人惊讶的是，很少有研究涉及这个问题，特别是在全面的群体基因组水平上。在此，我们证实水平基因流动和其他进化遗传变化对人类特异性病原体化脓性链球菌转录组的大量重塑是引发和持续流行疾病的核心因素。数据明确表明，这些分子事件的关键结果是一种新的、毒性更强的致病基因型的进化。我们的研究结果为流行病提供了新的认识。
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