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Characterisation of Streptococcus pneumoniae virulence factors and development of a proteins-based vaccine

  • Researchers:
    Dr James Paton
  • Start Date:
    01 January 2002
  • Category:
  • Location:
    Adelaide University, Adelaide, Australia

Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year. Pneumococci produce a variety of factors which are important in causing disease, but the relative contributions of these factors to each stage of the infection process remain to be determined. This project is aimed at gaining a complete understanding of the pathogenesis of pneumococcal disease, and using this information to develop a cheap and effective vaccine based on pneumococcal virulence proteins. This will involve extending our studies on the function and role in pathogenesis of putative pneumococcal virulence proteins, and identifying and characterizing additional proteins with the potential to contribute to pathogenesis. The relative importance of each protein will be determined by constructing mutations in the genes which encode them and determining the impact on virulence in a mouse model. We will then test the capacity of immunization with the above proteins, and combinations thereof, to elicit protection against challenge with diverse serotypes of S. pneumoniae in a mouse model.

Results from this study have been published in scientific journals as follows:

Stroeher UH, Paton AW, Ogunniyi AD, Paton JC.
Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model.
Infect Immun 2003 Jun;71(6):3206-12.

Kwon HY, Ogunniyi AD, Choi MH, Pyo SN, Rhee DK, Paton JC.
The ClpP protease of Streptococcus pneumoniae modulates virulence gene expression and protects against fatal pneumococcal challenge.
Infect Immun 2004 Oct;72(10):5646-53.

Standish AJ, Stroeher UH, Paton JC.
The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae.
Proc Natl Acad Sci U S A 2005 May 24;102(21):7701-6.

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