Scientists have created detailed image of Toxin Pneumolysin

Figure shows the way that copies of the toxin pack together to form pores in cells. Credit: University of Leicester

It gives hope for developing Rx for pneumococcal diseases such as bacterial pneumonia, meningitis and septicaemia. The 3 yr study involving 4 research groups from across the University has been described as an exciting advance because it points to the possibility of creating therapeutics that block assembly of pneumolysin pores to treat people with pneumococcal disease.

Using X-ray crystallography at Diamond Light Source, UK’s national synchrotron science facility, the Leicester team was able to see the individual atoms of the toxin. The structure not only reveals what the toxin looks like, but also shows how it assembles on the surface of cells to form lethal pores. When they disrupt these contacts, the toxin becomes inactivated so can no longer kill cells. The mode of action of pneumolysin action appears to be conserved in related toxins from other disease-causing bacteria e.g. toxins produced by pathogenic species of Listeria.

Professor Wallis said: “Our research is about a toxin called pneumolysin produced by a bacterium called pneumococcus (aka Streptococcus pneumoniae). …The World Health Organization (WHO) estimated that more than 1.6 million people die every year from pneumococcal infections, including more than 800,000 children under 5 years old.

The University of Leicester set up a spin-out company to find drugs that target the toxin. Professor Wallis said: “The work is especially exciting because of the importance of pneumolysin towards pneumococcal disease and the devastating consequences of pneumococcal infections. Our work has provided new insight into how the toxin kills cells…Overall it has been a real collaborative effort between four research groups across the College of Medicine, Biological Sciences and Psychology involving the groups in the Department of Infection, Immunity and Inflammation as well as the groups of Prof Peter Moody and Dr El-Mezgueldi in the Department of Molecular and Cell Biology.” https://www2.le.ac.uk/offices/press/press-releases/2015/november/scientists-2018see2019-detailed-make-up-of-deadly-toxin-for-the-first-time

http://www.nature.com/articles/srep13293