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和工程师新型微生物解决方案的基本规则提供了令人兴奋的途径。然而，合成微生物组对环境扰动的鲁棒性仍然相对未经测试。一类主要的微生物组扰动源于诸如噬菌体病毒（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所使用的表面受体来发展对噬菌体的抗性，但由于表面因素在介导环境相互作用中的重要性，这可能会对细菌的功能能力和物种相互作用产生重大影响。从综合社区的角度来看，对噬菌体暴露的响应风险损害了社区的功能能力，对表面因子的变化进行了变化。细菌还可以通过其“适应性免疫”机制（称为CRISPR-CAS）发展噬菌体的抗性，这些机制使细胞的功能能力完好无损，但是在实验室环境中很少能看到这种获得的抗性途径。 Lab CRIS-CAS演变的匮乏（由于噬菌体暴露而缺乏间隔者获取）对我们对CRISPR-CAS的理解作为获得的主要抗药性机制提出了挑战。我们假设CRISPR-CAS免疫获取是内部和特异性细胞间信号传导机制（AIM 1）和社区依赖性健身成本（AIM 2）的新兴特性，共同促进了强大的社区功能。我们进一步假设，可以预测噬菌体暴露对社区绩效的监管（AIM 1）和生态进化（AIM 2）的影响是可以预测的，并且给定有关物种相互作用和可用机制的信息。