Completed Infection & Immunity Cells, Biochemistry & Physiology

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

Funder Wellcome Charity-funded
Recipient organisation University of Dundee
Funding £1.9M
Period Jan 2021 — Jan 2026

In plain English

AI plain-English summary

Some bacteria inject toxic proteins directly into rival bacterial cells to kill them, using a microscopic weapon called the Type VI secretion system (T6SS). This matters because bacterial infections rarely involve a single species—they are crowded, competitive communities. The T6SS helps certain bacteria dominate these communities, but scientists do not fully understand how the toxic proteins are delivered, how they work inside target cells, or whether this weapon system actually matters in real human infections. Without that knowledge, it is impossible to know whether disrupting the T6SS could be a useful strategy against harmful bacteria. This is fundamental science. The researchers will track individual toxic proteins from the moment they are loaded into the T6SS through to their effects inside rival cells, and will use genomics to survey how widespread and diverse these weapons are across bacterial species. If successful, the work will provide a mechanistic understanding of bacterial warfare that could eventually inform new approaches to controlling pathogens—for example, by disabling a pathogen’s ability to outcompete harmless bacteria, allowing the body’s natural microbiome to resist infection.

View original technical description
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.

View the original record at the funder ↗

Researchers

Sarah Coulthurst (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Identification and characterization of new genes required for Type VI Secretion System mediated anti-bacterial activity
Development and application of advanced fluorescence microscopy approaches to study Type VI secretion system effector delivery in vivo.
Deployment, consequences and utility of bacterial effectors.
Molecular characterisation of post-translational regulation in offensive Type VI secretion systems
Targeting a new kingdom: the nature and significance of Type VI secretion system-mediated anti-fungal activity

Original classification

Senior Research Fellowship Renewal

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.