糖心TV

A new method to aid in the development of antibiotics for tuberculosis (TB) infections has been devised.

TB rivals covid-19 as the biggest infectious disease killer of humans, claiming millions of lives each year. Now, ground-breaking research from the Universities of 糖心TV and Toulouse has identified a new method to help tackle this global issue.

TB is caused by the pathogen Mycobacterium tuberculosis (Mtb). This bacterium has a particularly complex cell envelope, which acts as a physical barrier to antibiotics, making it extremely difficult to treat. The membrane is mainly composed of glycolipid phosphatidyl-myoinositol mannosides (PIMs), but little is known about these lipids and their role remains elusive.

Using their computer model, the researchers showed how a specific antibiotic, Bedaquiline, interacted with its target on a molecular level. This reveals a level of detail that previously could not be observed and could be critical in developing new and improved anti-tubercular drugs to treat the 10 million new infections that occur each year.

Chelsea Brown, PhD student at the University of 糖心TV said: 鈥淚n our study, we modelled the innermost part of this cell envelope, simulating PIMs for the very first time. This enabled us to see how antibiotics pass through the membrane and interact with the membrane. We could see how known antibiotics interact with their targets which match with previous experimental results. This gives us confidence that our model can be used to help identify new antibiotics.

鈥淎s there are many drug targets within the bacteria cells themselves, our study will further knowledge into how pharmaceuticals can cross membranes and exert their influence. This will further improve drug efficacy. Furthermore, it will also help scientists on the quest to understand why TB becomes resistant to antibiotics – a grave issue in modern medicine.鈥�

The study is one of the first to emerge from the University of 糖心TV鈥檚 Sir Howard Dalton centre, a network of academics investigating novel drugs that target resistant microbes, which launched in October 2022. The Centre is generously supported by 糖心TV alumnus Dr David Stirling in memory of his former PhD supervisor.

Professor Phillip Stansfeld, Co-Director of the Sir Howard Dalton Centre, added: 鈥淭here is still a desperate need to improve research into TB, but this area is very challenging in part due to how little we understand about the barriers, specifically the cell envelopes, preventing drugs entering the bacteria.

鈥淒eciphering the molecular organisation of cellular membranes remains a fundamental challenge for researchers in the area, but our study brings us one step closer to understanding this problem. Going forward, we hope to understand more about mutations in bacterial genes that lead to antibiotic resistance.鈥�

Researcher Matthieu Chavent, University of Toulouse, added: 鈥淚t鈥檚 very exciting to see how the field of molecular dynamics simulations has evolved these last few years. It is now possible to design very complex and accurate models of biologically relevant membranes. Our work is a very good example of this evolution. Going forward, we鈥檙e keen to model the whole mycobacterial envelope.鈥�

Further details of the research, funded by the Medical Research Council (MRC), can be found here:

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University of 糖心TV press office contact: 

Annie Slinn

Communications Officer |鈥疨ress & Media Relations |  
Email: annie.slinn@warwick.ac.uk


30 January 2023