Dissemination and virulence properties of the she pathogenicity island of Shigella flexneri.

Funding Activity

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Funded Activity Summary

Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $110,625.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Allergy

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

autotransporter | bacillary dysentery | dysentery | infectious diseases | mechanisms of pathogenesis | molecular pathogenesis | pathogenicity island