Active Infection & Immunity Genetics & Molecular Biology

Identifying a novel polymorphic toxin system in Gram-positive bacteria and determining the activity and mechanism(s) of action

Funder Wellcome Charity-funded
Associated organisations University of Dundee · University of Manchester Europe PMC affiliations are not treated as award recipients or mapped locations.
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

Bacteria deploy protein weapons to kill their rivals, and a newly discovered arsenal—the S8-polymorphic toxin system (S8-PTS)—is almost entirely unexplored. This matters because bacteria live in crowded, competitive communities, and understanding how they kill each other reveals the hidden rules of microbial survival. The S8-PTS was identified only recently, so researchers do not yet know which bacterial species carry these toxins, which species are vulnerable to them, or how the toxins actually enter and destroy target cells. Without this knowledge, a major mechanism of bacterial warfare remains a black box. The project will first scan bacterial genomes to map where S8-PTS clusters exist. Then, by isolating toxin-resistant mutants and sequencing their DNA, the team will pinpoint the genes that allow toxins to breach a cell’s defences. This is fundamental science—there is no immediate medical or industrial application. But past discoveries of bacterial killing systems, such as bacteriocins and type VI secretion systems, have led to new antibiotics and precision probiotics. A deeper grasp of S8-PTS could eventually open similar routes for engineering microbial competition or controlling harmful bacteria in the environment.

View original technical description
Bacteria exist in polymicrobial communities where they must compete for space and nutrients. Correspondingly, microbes have evolved survival mechanisms that allow them to out-compete other microorganisms. One such mechanism is “interference competition”, whereby one bacterial cell actively kills or disables another, often using proteins that are toxic. There is a newly discovered toxin system that is used for inter-bacterial killing, called the S8-polymorphic toxin system (S8-PTS). The S8-PTS was only recently identified and there are many unanswered questions. We aim to determine if there is species specificity for different toxin families and determine the range of species the toxin is active against and within. This aim will initially require a computational analysis of all the S8-PTS clusters in bacteria. Using the information obtained, we will be able to explore the activity of S8-PTS clusters in different species and establish the range of organisms susceptible to the toxins. To elucidate the mechanism(s) of toxin entry to susceptible cells, we will isolate S8-toxin resistant clones and sequence their whole genome. We will identify the location of mutations and use these to understand mechanism of toxin entry into the cell. This work will aid our understanding of how bacteria interact in the environment.

View the original record at the funder ↗

Researchers

Amy Wood (EPMC Awardee)David Leigh (EPMC Awardee)

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Original classification

PhD Studentship (Basic)

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