Pathogenesis of clostridial myonecrosis

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The aim of this project is to provide a better understanding of the mechanisms underlying the development of gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer. Although research has been carried out on this disease for many years prompt surgical removal of the infected tissue, often including amputation of a limb, is still commonly used to ensure the patient's survival. This project involves the study of the two bacteria that are the major causes of the disease. We aim to find out how the bacteria mediate the disease, in particular to determine which toxic factors produced by the bacteria are involved. The normal host response to a bacterial infection is a rapid influx of white blood cells to the infected tissue, which is part of the normal inflammatory response. These cells engulf and degrade the bacteria, clearing the infection. However, a major characteristic of gas gangrene pathology is that very few white blood cells infiltrate the infected tissue. We aim to determine why the host fails to mount an inflammatory response to this bacterial infection. We will achieve this objective by developing a better understanding of the role of the bacterial toxins in the development of this morbid disease. It is hoped the results from this study will enable the development of more effective therapeutic and prophylactic treatments for this disease and also provide a foundation for studies into the modulation of the host response by other bacterial species.