22-BBSRC/NSF-BIO: Community-dependent CRISPR-cas evolution and robust community function

22-BBSRC/NSF-BIO：群落依赖性 CRISPR-cas 进化和强大的群落功能

• 批准号: BB/Y008774/1
• 负责人: Edze Rients Westra
• 金额: $ 58.88万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY008774%2F1
• 关键词: 22; BBSRC; NSF; BIO; Community

Rationally designed synthetic microbial communities offer an exciting avenue to decipher basic rules of microbial organization and engineer novel microbial solutions to pressing applied challenges. Yet, the robustness of synthetic microbiomes to environmental perturbations remains relatively untested. A major class of microbiome perturbation stems from assault by molecular parasites such as bacteriophage viruses (phages). Individual species commonly evolve resistance to phages by modifying or entirely deleting the surface receptor used by the phage, but this can have substantial impacts on the functional capacities and species interactions of the bacterium, due to the importance of surface factors in mediating environmental interactions. In a synthetic community perspective, evolved surface factor modifications in response to phage exposure risk damaging the functional capacities of the community. Bacteria can also evolve resistance to phages via their 'adaptive immunity' mechanism, known as CRISPR-Cas, which leave the functional capacity of the cell intact, yet this pathway of acquired resistance is rarely seen in a lab setting. The paucity of lab CRISPR-Cas evolution (lack of spacer acquisition in response to phage exposure) presents a challenge to our understanding of CRISPR-Cas as a primary mechanism of acquired resistance. We hypothesize that CRISPR-Cas immunity acquisition is an emergent property of intra- and inter-specific cell-cell signaling mechanisms (Aim 1) and community-dependent fitness costs (Aim 2), which together promote robust community functioning. We further hypothesize that the regulatory (Aim 1) and eco-evolutionary (Aim 2) impacts of phage exposure on community performance are predictable, given information on species interactions and available mechanisms of phage resistance.

合理设计的合成微生物群落为破译微生物组织的基本规则和设计新颖的微生物解决方案以应对紧迫的应用挑战提供了令人兴奋的途径。然而，合成微生物组对环境扰动的稳健性仍然相对未经测试。一类主要的微生物组扰动源于噬菌体病毒（噬菌体）等分子寄生虫的攻击。单个物种通常通过修改或完全删除噬菌体使用的表面受体来进化对噬菌体的抗性，但这可能对细菌的功能能力和物种相互作用产生重大影响，因为表面因素在介导环境相互作用中的重要性。从合成群落的角度来看，响应噬菌体暴露而进化的表面因子修饰可能会损害群落的功能能力。细菌还可以通过其“适应性免疫”机制（称为 CRISPR-Cas）进化出对噬菌体的抗性，该机制使细胞的功能能力保持完整，但这种获得性抗性途径在实验室环境中很少见。实验室 CRISPR-Cas 进化的缺乏（缺乏响应噬菌体暴露的间隔区获得）对我们理解 CRISPR-Cas 作为获得性抗性的主要机制提出了挑战。我们假设 CRISPR-Cas 免疫获得是特定内和特定间细胞信号传导机制（目标 1）和群落依赖性适应性成本（目标 2）的新兴特性，它们共同促进了强大的群落功能。我们进一步假设，考虑到物种相互作用和噬菌体抗性的可用机制的信息，噬菌体暴露对群落表现的监管（目标 1）和生态进化（目标 2）影响是可以预测的。