Unravelling the molecular mechanisms of invasive pneumococcal disease

The bacterium Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. The most dangerous "serotype 1" strains, that are often multi-antibiotic resistant, have a cell-surface capsule made of specific sugar-chains. This project is motivated by the urgent need to understand how serotype 1 strains cause severe disease and to develop a low-cost vaccine against them. Recently, we have (i) studied patients in Malawi and The Gambia to provide further clues to why some S. pneumoniae strains can cause severe infections, (ii) overcome technical limitations to create mutant serotype 1 strains to facilitate laboratory studies. We will now undertake several co-ordinated studies to work out precisely how and why serotype 1 strains are so effective at causing severe disease. In addition, we will use our knowledge of bacterial capsules to produce a novel S. pneumoniae vaccine that will be affordable in the geographical regions where it is needed most.