CAREER: Microbiome regulation by amphibian skin peptides

职业：两栖动物皮肤肽对微生物组的调节

• 批准号: 1845634
• 负责人: Douglas Woodhams
• 金额: $ 97.9万
• 依托单位: University of Massachusetts Boston
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845634&HistoricalAwards=false
• 关键词: CAREER; Microbiome; regulation; amphibian; skin

Microbes, including bacteria and fungi, are in constant interaction with the immune system. Little is known about how this relationship helps prevent disease. Thus host-microbe biology is an exciting frontier for discovery. Amphibians are an excellent model system to study the symbiotic relationships between animal hosts and microbes because their moist skin surfaces have properties similar to the human digestive tract and lungs. The current award will use this model to test whether peptides secreted onto the skin of the northern leopard frog regulate skin microbiota by supporting the growth of beneficial bacteria and by inhibiting the growth of pathogenic bacteria. The results of this study will inform microbial therapies and contribute to conservation efforts as well. Since one third of the world's amphibian species are currently threatened, this research will also inform amphibian disease management and conservation at a critical time when continued disease emergence is harming biodiversity. Central to the NSF CAREER award, this project integrates research with education by implementing a Mentored Research Lab course on Microbiome and Disease Ecology to provide authentic research experiences. In learning communities, graduate students and postdoctoral researchers will give mentorship to undergraduates. An advisory board of microbial and disease ecologists, professional education specialists, and faculty will provide collaboration and training. The project will target recruitment from underrepresented groups at all levels. In this collaborative setting, students will be encouraged to design experiments on the cutting edge of host-microbe biology. Emerging infectious diseases threaten wildlife populations. Chytridiomycosis is one example of an emerging infectious disease of amphibians, such as leopard frogs, and is caused by the fungus Batrachochytrium dendrobatidis. This project will describe key interactions of host peptides and symbiotic microbes for defending the host against fungal infections and identify a novel mechanism of microbiome regulation by skin defense peptides. The central hypothesis is that amphibian skin peptides regulate the skin microbiome, thus impacting host-pathogen interactions. Specific objectives are: (1) Identify interactions between skin defense peptides and microbiota under field and controlled mesocosm conditions including comparisons among host life-history stages with different peptide expression patterns, (2) test if host skin peptides support microbes isolated from hosts (promicrobial function) and inhibit potentially invasive environmental microbes (antimicrobial function), (3) examine the role of defense peptides in regulating microbiome stability by experimentally reducing skin peptides and testing for microbial dysbiosis under different environmental conditions, and (4) test the role of microbial community phylogenetic diversity prompting complexity of host defense peptide expression on the skin through controlled experiments. Determining the trajectory of the microbiota through time under different environmental conditions will provide insight on whether microbiome assembly is stochastic, resilient, or adaptively shifts as defense peptides regenerate.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.

微生物，包括细菌和真菌，与免疫系统不断相互作用。关于这种关系如何有助于预防疾病，人们知之甚少。因此，宿主微生物生物学是一个令人兴奋的发现前沿。两栖动物是研究动物宿主和微生物之间共生关系的极好模型系统，因为它们潮湿的皮肤表面具有与人类消化道和肺相似的特性。目前的奖项将使用该模型来测试分泌到北方豹蛙皮肤上的肽是否通过支持有益细菌的生长和抑制致病细菌的生长来调节皮肤微生物群。这项研究的结果将为微生物疗法提供信息，并有助于保护工作。由于世界上三分之一的两栖动物物种目前受到威胁，这项研究还将在疾病持续出现损害生物多样性的关键时刻为两栖动物疾病管理和保护提供信息。NSF CAREER奖的核心，该项目通过实施微生物组和疾病生态学指导研究实验室课程，将研究与教育相结合，以提供真实的研究经验。在学习型社区中，研究生和博士后研究人员将为本科生提供指导。由微生物和疾病生态学家、专业教育专家和教师组成的咨询委员会将提供合作和培训。该项目的目标是从各级任职人数不足的群体征聘人员。在这种协作环境中，将鼓励学生设计宿主微生物生物学前沿的实验。新出现的传染病威胁着野生动物种群。壶菌病是一种新出现的两栖动物传染病，如豹蛙，是由真菌树芽壶菌引起的。该项目将描述宿主肽和共生微生物之间的关键相互作用，以保护宿主免受真菌感染，并确定皮肤防御肽调节微生物组的新机制。中心假设是两栖动物皮肤肽调节皮肤微生物组，从而影响宿主-病原体相互作用。具体目标是：（1）鉴定在野外和受控围隔条件下皮肤防御肽和微生物群之间的相互作用，包括比较具有不同肽表达模式的宿主生活史阶段，（2）测试宿主皮肤肽是否支持从宿主分离的微生物（促微生物功能）并抑制潜在的侵入性环境微生物（抗微生物功能），（3）通过实验性地减少皮肤肽并测试不同环境条件下的微生物生态失调来检查防御肽在调节微生物组稳定性中的作用，（4）通过对照实验验证微生物群落系统发育多样性对皮肤上宿主防御肽表达复杂性的促进作用。确定不同环境条件下微生物群随时间的轨迹，将有助于深入了解微生物群组装是随机的、有弹性的，还是随着防御肽的再生而适应性地变化。该奖项反映了NSF的法定使命，并通过使用基金会的智力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

Broad host susceptibility of North American amphibian species to Batrachochytrium salamandrivorans suggests high invasion potential and biodiversity risk.

• DOI: 10.1038/s41467-023-38979-4
• 发表时间: 2023-06-05
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Gray, Matthew J.;Carter, Edward Davis;Piovia-Scott, Jonah;Cusaac, J. Patrick W.;Peterson, Anna C.;Whetstone, Ross D.;Hertz, Andreas;Muniz-Torres, Aura Y.;Bletz, Molly C.;Woodhams, Douglas C.;Romansic, John M.;Sutton, William B.;Sheley, Wesley;Pessier, Allan;McCusker, Catherine D.;Wilber, Mark Q.;Miller, Debra L.
• 通讯作者: Miller, Debra L.

Preparatory immunity: Seasonality of mucosal skin defences and Batrachochytrium infections in Southern leopard frogs

• DOI: 10.1111/1365-2656.13386
• 发表时间: 2020-11-29
• 期刊: JOURNAL OF ANIMAL ECOLOGY
• 影响因子: 4.8
• 作者: Le Sage, Emily H.;LaBumbard, Brandon C.;Rollins-Smith, Louise A.
• 通讯作者: Rollins-Smith, Louise A.

Habitat split as a driver of disease in amphibians

• DOI: 10.1111/brv.12927
• 发表时间: 2023-01-04
• 期刊: BIOLOGICAL REVIEWS
• 影响因子: 10
• 作者: Becker, C. Guilherme;Greenspan, Sasha E. E.;Savage, Anna E. E.
• 通讯作者: Savage, Anna E. E.

The adaptive microbiome hypothesis and immune interactions in amphibian mucus

• DOI: 10.1016/j.dci.2023.104690
• 发表时间: 2023-05-16
• 期刊: DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
• 影响因子: 2.9
• 作者: Woodhams，Douglas C.;McCartney，Julia;Whetstone，Ross
• 通讯作者: Whetstone，Ross

Selection of an anti-pathogen skin microbiome following prophylaxis treatment in an amphibian model system

• DOI: 10.1098/rstb.2022.0126
• 发表时间: 2023-06
• 期刊: Philosophical Transactions of the Royal Society B
• 作者: Samantha A. Siomko;Sasha E. Greenspan;K. Barnett;Wesley J. Neely;Stanislava Chtarbanova;D. Woodhams;T. McMahon;C. Becker