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

持久性病原体的传播和进化：炭疽感染动态比较两个自然系统

• 批准号: 2106221
• 负责人: Wendy Turner
• 金额: $ 250万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2106221&HistoricalAwards=false
• 关键词: Transmission; evolution; persistent; pathogen; anthrax

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.

炭疽热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，对炭疽疫情的成功预测和应对受到限制。本项目将研究宿主、病原体和环境的作用，以了解病原体-宿主相互作用如何演变，并导致两个研究区域之间炭疽发生的差异。这两个地区都在南部非洲，它们的炭疽爆发动态非常不同，这代表了世界范围内炭疽系统的变化。在纳米比亚的埃托沙国家公园，每年雨季都会发生影响放牧斑马的小规模疫情。相比之下，在南非的克鲁格国家公园，影响观羚的大规模疫情发生在旱季，大约每十年发生一次。该项目建立在每个公园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重要组成部分。来自不同背景的博士后研究人员、本科生和研究生将接受实地、实验室和定量技术方面的培训，重点是前沿的基因组学、统计和动态建模方法。炭疽的病原体（炭疽芽孢杆菌），经常被引用为教科书的例子，为进化高毒力和长期的环境生存。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，以及最终这些过程如何驱动宿主-病原体共同进化。这个合作研究小组将比较两个野生动物系统中的炭疽动力学，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性之间的权衡？(2)宿主多样性如何影响病原体传播和毒力之间的权衡？(3)景观尺度的传播模式和宿主运动如何影响毒力传播权衡和宿主-病原体种群动态？研究人员将把炭疽芽胞杆菌基因组的变异与表型（即病原体在环境中的存活、对宿主的毒力以及跨宿主和地理范围的传播）联系起来。研究人员将在平原斑马（Equus quagga）和大羚羊（Tragelaphus strepsiceros）这两种主要宿主物种中鉴定病原体介导选择下的宿主基因。研究人员将建立包括宿主运动、传播途径、病原体毒力和宿主抗性在内的流行病学和种群动态的景观级模型。最后，研究人员将建立预测炭疽在生态系统中的传播动态的模型。从更广泛的意义上说，这项研究将有助于开发预测工具，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疾病。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Zebra anthrax carcass site pathogen and soil data from Namibia, 2010-2021

2010-2021 年纳米比亚斑马炭疽尸体病原体和土壤数据

• DOI: 10.5066/p9tday91
• 发表时间: 2023
• 期刊: U.S. Geological Survey
• 作者: Turner, Wendy C;Barandongo, Zoe
• 通讯作者: Barandongo, Zoe

Variation in herbivore space use: comparing two savanna ecosystems with different anthrax outbreak patterns in southern Africa.

• DOI: 10.1186/s40462-023-00385-2
• 发表时间: 2023-07-31
• 期刊: MOVEMENT ECOLOGY
• 影响因子: 4.1
• 作者: Huang, Yen-Hua;Owen-Smith, Norman;Henley, Michelle D.;Kilian, J. Werner;Kamath, Pauline L.;Ochai, Sunday O.;van Heerden, Henriette;Mfune, John K. E.;Getz, Wayne M.;Turner, Wendy C.
• 通讯作者: Turner, Wendy C.

The persistence of time: the lifespan of Bacillus anthracis spores in environmental reservoirs

时间的持久性：环境库中炭疽芽孢杆菌孢子的寿命

• DOI: 10.1016/j.resmic.2023.104029
• 发表时间: 2023
• 期刊: Research in Microbiology
• 影响因子: 2.6
• 作者: Barandongo, Zoë R.;Dolfi, Amelie C.;Bruce, Spencer A.;Rysava, Kristyna;Huang, Yen-Hua;Joel, Hendrina;Hassim, Ayesha;Kamath, Pauline L.;van Heerden, Henriette;Turner, Wendy C.
• 通讯作者: Turner, Wendy C.

Disease or drought: environmental fluctuations release zebra from a potential pathogen-triggered ecological trap.

• DOI: 10.1098/rspb.2021.0582
• 发表时间: 2021-06-09
• 期刊: Proceedings. Biological sciences
• 作者: Huang YH;Joel H;Küsters M;Barandongo ZR;Cloete CC;Hartmann A;Kamath PL;Kilian JW;Mfune JKE;Shatumbu G;Zidon R;Getz WM;Turner WC
• 通讯作者: Turner WC

Environmental drivers of biseasonal anthrax outbreak dynamics in two multihost savanna systems

两个多宿主稀树草原系统双季节炭疽爆发动态的环境驱动因素

• DOI: 10.1002/ecm.1526
• 发表时间: 2022
• 期刊: Ecological Monographs
• 影响因子: 6.1
• 作者: Huang, Yen‐Hua;Kausrud, Kyrre;Hassim, Ayesha;Ochai, Sunday O.;van Schalkwyk, O. Louis;Dekker, Edgar H.;Buyantuev, Alexander;Cloete, Claudine C.;Kilian, J. Werner;Mfune, John K. E.
• 通讯作者: Mfune, John K. E.