The fight for success: inter-bacterial competition mediated by the Type VI secretion system and its effectors

The Type VI secretion system (T6SS) is used by many Gram-negative bacteria to deliver toxic ‘effector’ proteins into rival bacterial cells as a means of inter-bacterial competition.

The T6SS likely plays a central role in shaping many polymicrobial communities, but important aspects of effector delivery and action in target cells, and the ‘real-life’ relevance of T6SSs in a clinical context remain elusive.

We will investigate the journey of individual and co-operating groups of effectors, from their recruitment by the T6SS to their fate and action in targeted cells, and dissect the mechanism of individual anti-bacterial effectors.

We will also consider the global availability and mobility of anti-bacterial effectors and how the T6SS and its effectors can influence bacterial success in a clinical context.

Using multidisciplinary approaches, we aim to: - Determine the mechanism of toxicity of novel anti-bacterial effectors - Elucidate the fate of effectors inside target cells - Define mechanisms of versatile effector recruitment and delivery in attacker cells - Use genomics to reveal the diversity, evolution and real-life relevance of T6SS effectors Our findings, combining mechanistic detail with insight into biological relevance, will provide fundamental advances in our understanding of T6SS-mediated anti-bacterial activity and may inform future strategies to counter bacterial pathogens.