Transmission and evolution of a persistent pathogen: anthrax infection dynamics comparing two natural systems

炭疽病是一种全球分布的野生动物、牲畜和人类疾病。由于缺乏对病原体生态的地理差异以及疾病暴发模式的了解，对炭疽暴发的成功预测和应对受到限制。这个项目将调查宿主、病原体和环境的作用，以了解病原体-宿主相互作用是如何演变的，并有助于两个研究地区之间炭疽病发生的差异。这两个地区都位于南部非洲，炭疽暴发动态非常不同，这代表了世界范围内炭疽病系统的变异。在纳米比亚的埃托沙国家公园，每年雨季都会有较小规模的疫情爆发，影响到放牧斑马。相比之下，在南非的克鲁格国家公园，更大规模的疫情会在旱季发生，影响觅食野狗的规模大约为十年。该项目建立在每个公园的疾病和种群动态的详细记录以及存档的病原体样本的基础上，并将涉及新的数据收集和分析以及数学建模，以了解这些不同的动态。教育、培训以及科学和公众宣传是这项研究的基本组成部分。来自不同背景的博士后研究人员、本科生和研究生将接受现场、实验室和定量技术方面的培训，重点是尖端基因组学以及统计和动态建模方法。炭疽病的病原体(炭疽芽孢杆菌)经常被引用为高毒力和延长环境生存的进化的教科书例子。该项目将连接宿主内、宿主间和环境内的过程，以了解相互冲突的选择压力如何影响病原体多样性、宿主抗性、疾病发病率，并最终了解这些过程如何推动宿主-病原体的共同进化。这个合作研究团队将比较两个野生动物系统中的炭疽菌动态，整合长期实地研究、宿主和病原体基因组学、微生物学以及统计和动态建模。该项目解决了三个相关问题：(1)病原体多样性如何影响病原体传播和毒力之间的权衡？(2)宿主多样性如何影响病原体传播和毒力之间的权衡？以及(3)传播和寄主移动的横向模式如何影响毒力-传播权衡和寄主-病原体种群动态？研究人员将把炭疽杆菌基因组的变异性与表型(即病原体在环境中的生存、对宿主的毒力以及跨宿主和地理范围的传播)联系起来。研究人员将在两个主要寄主物种--平原斑马(Equus Quagga)和大kudu(Traelphus Strepsiceros)--的病原体介导性选择下识别寄主基因。研究人员将建立包含宿主运动、传播途径、病原体毒力和宿主抗药性的流行病学和种群动力学的景观级模型。最后，研究人员将建立模型，预测炭疽病在生态系统中的传播动态。在更广泛的意义上，这项研究将促进预测工具的开发，以更好地管理公共卫生和相关政策，以应对炭疽等复杂的多宿主人畜共患病。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Anthrax is a globally distributed disease of wildlife, livestock, and humans. Successful prediction of and response to outbreaks of anthrax is limited by a lack of understanding of the geographic differences in the ecology of the pathogen as well as the pattern of disease outbreaks. This project will investigate the roles of host, pathogen, and environment to understand how the pathogen - host interaction evolves and contributes to the differences in anthrax occurrence between two study areas. The two areas, both in southern Africa, have very different anthrax outbreak dynamics, which are representative of variation in anthrax systems world-wide. In Etosha National Park, Namibia, there are smaller outbreaks, affecting grazing zebra, annually in wet seasons. In contrast, in Kruger National Park, South Africa, larger outbreaks affecting browsing kudu occur in dry seasons on roughly a decadal scale. The project builds on detailed records of disease and population dynamics in each park as well as archived pathogen samples and will involve new data collection and analyses and mathematical modeling to understand these different dynamics. Education, training, and scientific and public outreach are essential components of this research. Postdoctoral researchers and undergraduate and graduate students from diverse backgrounds will be trained in field, laboratory, and quantitative techniques emphasizing cutting-edge genomics, and statistical and dynamic modeling approaches. The causative agent of anthrax (the bacterium Bacillus anthracis), is often invoked as a textbook example for the evolution of high virulence and prolonged environmental survival. This project will link within-host, between-host, and in-environment processes, to understand how conflicting selective pressures impact pathogen diversity, host resistance, disease incidence, and ultimately, how these processes may drive host-pathogen co-evolution. This collaborative research team will compare anthrax dynamics in two wildlife systems, integrating long-term field studies, host and pathogen genomics, microbiology, and statistical and dynamic modeling. The project addresses three related questions: (1) how does pathogen diversity affect trade-offs between pathogen transmission and virulence? (2) how does host diversity affect trade-offs between pathogen transmission and virulence? and (3) how do landscape-scale patterns of transmission and host movement affect virulence-transmission trade-offs and host-pathogen population dynamics? Researchers will link variability in B. anthracis genomes to phenotype (i.e., pathogen survival in the environment, virulence to hosts, and transmission across host and geographic range). Researchers will identify host genes under pathogen-mediated selection in two primary host species, plains zebra (Equus quagga) and greater kudu (Tragelaphus strepsiceros). Researchers will build landscape-level models of epidemiology and population dynamics incorporating host movement, transmission routes, pathogen virulence, and host resistance. Finally, researchers will build models predicting anthrax transmission dynamics across ecosystems. In a broader sense, this research will facilitate the development of predictive tools to better manage public health and related policies for complex, multi-host zoonotic diseases such as anthrax.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.