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The role of pneumococcal factors in virulence and carriage

Abstract number: 1133_230

Mitchell T.J.

Streptococcus pneumoniae is a major pathogen of man, causing diseases such as pneumonia and meningitis. The mechanisms by which this organism causes disease are still unclear but certainly involve over-activation of inflammatory pathways. The organism produces a range of factors that may be involved in the pathogenesis of infection. These include a toxin (pneumolysin) as well as a range of surface proteins and enzymes. The polysaccharide capsule is essential for virulence of the organism. The availability of genome sequences of several strains of pneumococcus has allowed the identification of putative virulence factors and regulatory pathways. Use of this information in conjunction with in vitro systems and animal models allows the study of the role of these factors in disease. I will describe data we have on the role of surface proteins, the toxin pneumolysin and the heat shock protein HtrA in the virulence of Streptococcus pneumoniae. Pneumolysin is a major virulence factor of the organism and induces inflammation in the lung. Very small amounts of the toxin are able to induce inflammatory cytokine production. Surface proteins such as pneumococcal surface protien C (PspC) play a role in both attachment and interaction of the organism with the immune system. I will describe the use of genetically defined mutants of the pneumcooccus lacking PspC in animal models of infection. These studies show that the role of PspC in the disease process is different for different strains of the organism. HtrA is a heat shock protein of the pneumococcus and is probably acts as both a chaperone and protease to control protein folding and degrade misfolded proteins. We have shown that deletion of the gene for HtrA attenuates the pneumococcus in animal models of infection. This will allow us to investigate the possibility of using HtrA mutants as live vaccination vehicles. Several strains of the pneumococcus have have been subjected to total genome sequencing. Availability of these genome sequence allows the construction of microarrays and I will describe our use of these chips to study regulatory pathways in the pneumococcus. Analysis of gene expression in different serotypes of the pneumococcus suggests that there may be serotype specific regulatory pathways within the organism. This has implications for treatment and vaccination.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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