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

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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.