Cell bursting toxin the target of new vaccine

Becoming infected with the Streptococcus pneumoniae bacterium is definitely something to avoid. Not only is it a leading cause of pneumonia and other serious conditions such as bronchitis, bacterial meningitis, and sepsis, it is also a significant source of mortality among young children in developing countries.

Thankfully, researchers at St Vincent’s Institute of Medical Research in Melbourne, in collaboration with scientists from the Bio21 Institute at the University of Melbourne, and the University of Oklahoma in the USA, have made a breakthrough in the fight against this deadly bacterium.

Professor Michael Parker, who recently co-authored the findings in the journal Scientific Reports, says developing an effective vaccine has proved challenging as there are more than 90 strains of S. pneumonia, some of which have become resistant to current treatments.

The team of researchers have been analysing the three-dimensional structures of proteins associated with S. pneumonia using the Australian Synchrotron, a giant X-ray microscope at Clayton in Melbourne’s south-east.

Pneumolysin – a doughnut-shaped, pore-forming, toxic protein – is of significant interest. While cellular damage by this toxin is well established, scientific advancement has come in the form of identifying the initial structural changes that occur before the protein becomes active.

“Pneumolysin first recognises human cells by binding to cholesterol in the cell membrane,” Professor Parker explains. “From here the protein assembles in a linear arrangement on the cell surface before it folds into doughnut-shaped rings that can cause large holes to form in the cell membrane and allow the cell’s essential nutrients to escape.”

Unlike the varying proteins found among the many different strains of S. pneumonia, the pneumolysin protein is present among all clinical strains. Therefore, developing ways to target pneumolysin before it can burst cell membranes and kill cells is a critical step in developing new and more effective vaccines against pneumococcal disease.

“New protein-based pneumococcal vaccines are increasingly being investigated to eliminate the necessity of capsule-based vaccines”, Professor Parker says.

The older style vaccines against pneumococcal disease consisted of polysaccharides – long chains of sugar molecules – acting as a carrier for a protein or antigen from the bacteria likely to cause an immune response. However, studies have found that such vaccines often have limited effective protective immunity.

With the pneumolysin structure providing the crucial basis for further experimentation, development of new treatments concerning S. pneumonia could be imminent.

Professor Michael Parker is Deputy Director of St Vincent’s Institute of Medical Research, and a University of Melbourne Honorary Professorial Fellow affiliated with the Department of Biochemistry and Molecular Biology at the Bio21 Institute. His significant achievements have recently been recognised with his election to Fellowship of the Australian Academy of Health and Medical Sciences.

By Esther Lloyd