Associated organisationsHeriot-Watt University · Natural Product Research and Infection Biology – Hans Knöll Institute · Newcastle University · University of Dundee · University of ExeterEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£2.7M
PeriodJun 2019 — Jun 2024
In plain English
AI plain-English summary
Bacteria can deploy a molecular harpoon—the Type VI secretion system (T6SS)—to stab and kill rival fungi, a weapon only recently discovered by this team. Most research on bacterial competition has focused on bacteria attacking other bacteria. This project addresses a blind spot: bacteria also live alongside fungi in the human gut, on skin, in soil, and on crops. The team found that some bacteria use the T6SS to inject toxic proteins that kill fungal cells through distinct mechanisms. They now want to know how widespread this anti-fungal activity is, how the bacterial weapon interacts with fungal cells, and exactly how the delivered toxins work. This is fundamental science—there is no immediate medical or agricultural application. The researchers are mapping a new biological battlefield. Understanding how bacteria naturally suppress fungi could eventually inform the design of anti-fungal therapies, especially as drug-resistant fungal infections rise. It might also explain why certain microbial communities resist fungal overgrowth, with implications for crop protection or managing infections in vulnerable patients. But for now, the goal is simply to understand what these bacterial weapons do and how they work.
View original technical description
Microbial organisms, including bacteria and fungi, normally live in mixed communities whose members interact co-operatively or competitively by a variety of mechanisms. 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 interbacterial competition. We recently discovered that the T6SS can also be used as a potent weapon against fungal competitors and identified the first fungal-specific T6SS effector proteins, which cause fungal cell death via distinct mechanisms. We propose that T6SS-mediated anti-fungal activity is widespread, mediated by a variety of effector proteins and able to shape diverse polymicrobial communities, including those important for human health and disease. In this project, we have assembled an expert, multi-disciplinary team to investigate the nature, role and molecular basis of T6SS-mediated anti-fungal activity. Our specific Aims are to: - Examine the distribution and significance of T6SS-mediated anti-fungal activity - Understand the interaction between the fungal cell and the bacterial T6SS - Define the mode of action of T6SS-delivered anti-fungal effectors Our findings will illuminate the fundamental mechanism and biological relevance of T6SS-mediated anti-fungal activity, whilst paving the way for potential future anti-fungal therapeutic developments.
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