Characterisation and vaccine potential of pneumococcal virulence factors expressed during meningitis

Current research

Streptococcus pneumoniae is now the commonest cause of meningitis in children and older adults. The prevalence of antibiotic-resistant pneumococci is increasing rapidly, and available vaccines have major shortcomings. The factors and/or events that trigger the progression from colonization to invasive pneumococcal disease, including meningitis in certain individuals, are poorly understood, but presumably require expression of a distinct array of bacterial genes. Specifically, the critical determinants that enable pneumococci to cross the blood-brain barrier are largely unknown. The contribution of choline binding protein A (CbpA, also called PspC or SpsA) to pneumococcal meningitis is well documented. However, our unpublished observations show that immunization of mice with CbpA did not afford adequate protection against pneumococcal meningitis, suggesting that virulence factors other than CbpA are likely involved. This proposal is aimed at identification and detailed characterisation of such virulence factors, and assessing their vaccine potential in a murine model. Preliminary mouse intranasal challenge experiments in our laboratory with virulent pneumococcal strains D39 (serotype 2), WCH43 (serotype 4), and WCH16 (serotype 6A) indicated that WCH16 and WCH43 had a greater propensity to translocate to the brain within 72 h, than D39. We aim to carry out a comprehensive global analysis of pneumococcal gene expression patterns in these strains to identify factors critical to the development of pneumococcal meningitis. These studies will provide an improved understanding of the pathogenesis of pneumococcal meningitis, as well as critical information required to ensure that protein-based pneumococcal vaccines currently under development are effective against meningitis.