Bilateral NSF/BIO-BBSRC The roles of contact-dependent inhibition in building mixed bacterial communities

双边 NSF/BIO-BBSRC 接触依赖性抑制在建立混合细菌群落中的作用

• 批准号: BB/M023044/1
• 负责人: Marjan Van Der Woude
• 金额: $ 65.31万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM023044%2F1
• 关键词: Bilateral; NSF; BIO; BBSRC; roles

Bacteria are essential to human, animal health, and plant health, but can also cause disease. Bacteria are usually found working together as well-ordered communities. Understanding how communities develop and are maintained is therefore very important. One of the applicants discovered a system used by a range of bacterial species to inhibit the growth of others: contact dependent inhibition (CDI). In this elegant system one bacterial cell, the inhibitor, injects a toxin into a susceptible bacterium (target) when they touch, which inhibits target cell growth. There is evidence of many different types of these toxins in nature, but we do not yet know how they all work, and why they are so prevalent. In this project we will examine how CDI affects the development of mixed strain bacterial communities. We will use and integrate three different approaches. Firstly, we will study how these toxins work in detail to gain a clear understanding of the changes the target cell undergoes when it is growth inhibited. This will be achieved by a combination of microbial genetics, molecular biology and biochemistry approaches. Second, using advanced microscopy techniques and strains with well-characterized CDI systems, we will document growth and inhibition in real time. We will measure different aspects, including how fast the toxin acts, and whether target cells can recuperate. Finally, based on the knowledge of CDI gained from these molecular and microscopic studies, we will use mathematical approaches to generate, and then also test, predictive computer models of the effect of CDI on bacterial communities. CDI toxins are present in many different bacteria and based on similarities, the project can contribute new insight into a wide range of microbiological systems, and thus the understanding we generate may be exploited to address different societal challenges. In health care, probiotics build and maintain beneficial bacterial communities, and the understanding of CDI effects on populations may be exploited to improve probiotic strains or probiotic-based strategies. Similarly, approaches to improve plant health may devised where we encourage and help beneficial bacterial communities to grow. Both academics and pharmaceutical companies may be inspired by the understanding of CDI toxin activity to pursue new approaches to antimicrobial drug development. Finally, we envision that CDI systems may be introduced in industrial processes or in synthetic biology systems, where it is important to control mixed strain bacterial populations, for example in live biosensors. We will organize a workshop with academics and industrial representatives to stimulate discussion on applications of CDI. We also will share our enthusiasm and knowledge of this research with talks and activities for the public and at schools, colleges and universities.

细菌对人，动物健康和植物健康至关重要，但也可能引起疾病。通常发现细菌作为有序的社区一起工作。因此，了解社区如何发展和维护非常重要。其中一位申请人发现了一系列细菌物种使用的系统来抑制其他物种的生长：接触依赖性抑制（CDI）。在这个优雅的系统中，一种细菌细胞抑制剂在接触时将毒素注入易感细菌（靶），从而抑制靶细胞生长。有许多不同类型的毒素的证据，但我们尚不知道它们都是如何工作的，为什么它们如此普遍。在这个项目中，我们将研究CDI如何影响混合菌株细菌群落的发展。我们将使用并整合三种不同的方法。首先，我们将研究这些毒素如何详细起作用，以清楚地了解目标细胞在生长抑制时发生的变化。这将通过微生物遗传学，分子生物学和生物化学方法的结合来实现。其次，使用具有良好特征的CDI系统的高级显微镜技术和菌株，我们将实时记录生长和抑制作用。我们将测量不同的方面，包括毒素的作用速度，以及靶细胞是否可以恢复。最后，基于从这些分子和微观研究中获得的CDI知识，我们将使用数学方法来生成CDI对细菌群落的影响的预测计算机模型。 CDI毒素存在于许多不同的细菌中，并且基于相似性，该项目可以对广泛的微生物系统产生新的见解，因此我们可以利用我们产生的理解来应对不同的社会挑战。在卫生保健中，益生菌建立和维持有益的细菌群落，对CDI对人群的影响的理解可能会被利用以改善益生菌菌株或基于益生菌的策略。同样，在我们鼓励并帮助有益的细菌群落成长的地方可以设计改善植物健康的方法。学术界和制药公司都可能受到对CDI毒素活动的理解，以寻求新的抗菌药物开发方法。最后，我们设想可以在工业过程或合成生物学系统中引入CDI系统，在该系统中，控制混合菌株细菌种群很重要，例如在实时生物传感器中。我们将与学者和工业代表组织一个研讨会，以刺激有关CDI应用的讨论。我们还将与公众以及学校，学院和大学的会谈和活动分享我们对这项研究的热情和知识。