Host and Aquatic Environment Dependent Cost and Benefits of the Shigella Flexneri Virulence Plasmid and Shiga Toxin Production

弗氏志贺氏菌毒力质粒和志贺毒素生产的宿主和水生环境依赖性成本和效益

• 批准号: 10397676
• 负责人: Thomas Gene Platt
• 金额: $ 23.78万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10397676
• 关键词: Amoeba genus; Animals; Cells; Communicable Diseases; Complex; Cost Measures; Costs and Benefits; Emerging Communicable Diseases; Ensure; Environment; Eukaryota; Event; Evolution; Exotoxins; Gene Expression; Genes; Genotype; Hemorrhagic colitis; Heterogeneity; Human; Lead; Maintenance; Mediating; Molecular; Molecular Evolution; Mutation; Pathogenesis; Pathogenicity; Phenotype; Plasmids; Population; Predatory Behavior; Production; Public Health; Regulon; Research; Research Personnel; Role; Shiga Toxin; Shigella; Shigella Infections; Shigella dysenteriae; Shigella flexneri; Shigella sonnei; System; Testing; Tetrahymena thermophila; Virulence; Virulence Factors; Work; Zoonoses; cost; diarrheal disease; experience; experimental study; fitness; human pathogen; life history; mutant; novel; pathogen; pressure; transmission process; waterborne

Project Summary/Abstract: Many emerging infectious diseases maintain significant populations outside of host environments. The consequences of dynamics occurring in these environmental reservoirs on the pathogenesis of these pathogens is seldom investigated and poorly characterized. This project examines how the molecular systems that facultative pathogens use to exploit hosts are shaped by the consequences of dynamics occurring within both host and environmental reservoir environments. Specifically, the researchers aim to test the hypothesis that context dependent costs and benefits result in selective dynamics within aquatic environments that lead to loss of Shigella flexneri virulence plasmid encoded virulence factors while promoting the maintenance of chromosomally encoded Shiga toxin production. The researchers will use a combination of competition experiments to measure the costs and benefits of pINV virulence plasmid carriage and virulence regulon expression in both host and aquatic environments. Further the researchers will determine how Shiga toxin expression in host and aquatic environments influences the fitness of pathogenic Shigella. Finally, the researchers will test predictions with respect to the evolutionary dynamics of both pINV encoded and Shiga toxin virulence factors using an experimental evolution approach. The researchers predict that increased duration of bouts of selection within aquatic reservoirs will result in the spread of non-invasive Shigella while the presence of Tetrahymena thermophila predation in these reservoirs will result in increased Shiga toxin production. The proposed work will determine the context dependent fitness consequences of Shigella virulence factors and determine whether selection in environmental reservoirs may contribute to the recent emergence of novel Shiga toxin producing Shigella pathogens.

项目概要/摘要： 许多新出现的传染病在宿主环境之外维持着大量的人口。的 这些环境水库中发生的动态对这些疾病发病机制的影响 病原体很少被研究，也没有得到很好的表征。这个项目研究了分子系统如何 兼性病原体利用宿主的方式是由宿主体内发生的动力学结果决定的， 宿主和环境储层环境。具体来说，研究人员的目标是测试假设 环境依赖的成本和收益导致水生环境中的选择性动态， 福氏志贺氏菌毒力质粒编码的毒力因子丢失，同时促进维持 染色体编码的滋贺毒素产生。研究人员将使用一种结合竞争 测量pINV毒力质粒携带和毒力调节子的成本和效益的实验 在宿主和水生环境中表达。研究人员将进一步确定滋贺毒素 在宿主和水生环境中的表达影响致病性志贺氏菌的适合度。最后 研究人员将测试pINV编码和滋贺的进化动力学预测 毒素的毒力因子使用实验进化的方法。研究人员预测， 在水生水库内持续的选择将导致非侵入性志贺氏菌的传播， 在这些储库中存在嗜热四膜虫捕食将导致滋贺毒素增加 生产拟议的工作将确定环境依赖的适应性后果的志贺氏菌 毒力因子，并确定环境水库的选择是否可能有助于最近的 新的产生滋贺毒素的志贺菌病原体的出现。