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The Humane Research Trust is funding a research project to help us understand the cellular mechanisms behind bacterial infection. The researchers at the University of Sheffield are using cell culture models to study the bacteria that causes meningitis. This research will provide greater insight into how bacteria can hijack human cells. These learnings will then lay the groundwork for the development of anti-infectives.
Infectious disease is a huge health burden globally. In addition, antibiotic resistance is on the rise; by 2050, experts predict it could cause 10 million deaths per year. Due to their rapid doubling time, bacteria can quickly evolve mechanisms to overcome drugs targeted to them.
To counter this issue, we must develop our understanding of how infectious disease works on a cellular level. To get inside our cells, bacteria must stick to and breach the surrounding membrane. This membrane consists of water-repelling fats and proteins. Bacteria do this by ‘hijacking’ the human proteins within the membrane.
However, researchers have not yet identified a universal mechanism which all bacteria use to get inside our cells. We know that different bacterial species hijack different cell membrane proteins, making it harder for scientists to devise effective treatments.
The Humane Research Trust is funding a research project at the University of Sheffield to learn more about bacterial infection. They hope to shed light on the cellular mechanisms that underly the process of infection. The researchers, led by Dr Luke Green, are focusing their study on the bacteria Neisseria meningitidis, which causes bacterial meningitis.
Currently, scientists typically conduct bacterial studies on modified mice. Dr Green hopes that his research project will change this. “This research poses the potential to generate a new human cell model for bacterial transit across the blood-brain barrier. This will reduce the need for animal models,” explains Dr Green. “Understanding precisely how bacteria stick to and enter our cells is paramount. This knowledge will aid scientists in developing new anti-infectives, reducing dependence on antibiotics and improving global health.”
Dr Green’s prior research uncovered that cell membrane proteins may play a key role in bacteria binding to our cells. He noticed that a particular family of proteins, the 'tetraspanins', acted as 'organisers' within human cell membranes. They brought together lots of other proteins to form large protein 'islands'. These islands functioned like adhesion platforms, helping the bacteria stick to the human cells.
One characteristic of Neisseria meningitidis is that it can rapidly change which 'sticky molecules' are on its surface. These changes can alter whether the bacteria cause disease or is harmlessly carried by the host. Dr Green thinks that the ability to change its surface molecules could help the bacteria manipulate the protein islands on human cells. His research group is currently using a cell culture model to test this hypothesis.
The researchers want to know whether bacteria directly manipulate the protein islands on human cells, or do so via altering their own cell surface. They also want to learn how the composition of the human cell membrane differs between different types of cells. This will help them understand how these variations affect infection potential. The Trust is delighted to fund this project. We hope the research will elucidate precisely how bacteria are able to cause infection.
