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

细菌对人类、动物和植物的健康至关重要，但也会引起疾病。细菌通常作为有序的群落一起工作。因此，了解社区如何发展和维持是非常重要的。其中一名申请者发现了一种被一系列细菌用来抑制其他细菌生长的系统：接触依赖性抑制（CDI）。在这个优雅的系统中，一个细菌细胞，即抑制剂，在它们接触时向易感细菌（目标）注入毒素，从而抑制目标细胞的生长。有证据表明，自然界中存在许多不同类型的毒素，但我们还不知道它们是如何起作用的，以及它们为什么如此普遍。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，我们将详细研究这些毒素是如何起作用的，以清楚地了解靶细胞在生长受到抑制时所经历的变化。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，利用先进的显微镜技术和具有良好表征的CDI系统的菌株，我们将实时记录生长和抑制。我们将测量不同的方面，包括毒素的作用速度，以及目标细胞是否可以恢复。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生成CDI对细菌群落影响的预测计算机模型，然后进行测试。CDI毒素存在于许多不同的细菌中，基于相似性，该项目可以为广泛的微生物系统提供新的见解，因此我们产生的理解可能被用来解决不同的社会挑战。在医疗保健中，益生菌建立和维持有益的细菌群落，了解CDI对种群的影响可以用来改善益生菌菌株或基于益生菌的策略。同样，改善植物健康的方法也可以在我们鼓励和帮助有益细菌群落生长的地方设计出来。学术界和制药公司可能会受到CDI毒素活性的理解的启发，以寻求抗菌药物开发的新方法。最后，我们设想CDI系统可能会被引入到工业过程或合成生物学系统中，在这些系统中，控制混合菌株细菌群是很重要的，例如在活的生物传感器中。我们将举办由学术界和业界代表参与的研讨会，以促进对综合数据中心应用的讨论。我们还将在学校、学院和大学为公众举办讲座和活动，分享我们对这项研究的热情和知识。

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.