Sharif, Amin A.; (1991) The toxicity of Mycobacterium ulcerans. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The mycobacterial genus is responsible for two of the most devastating diseases of man, namely tuberculosis and leprosy. In addition to these two classical diseases, there are a number of specific and non-specific infections due to mycobacteria. Such infections are rare compared to tuberculosis and leprosy, but they may cause crippling or even fatal diseases. Mycobacterium ulcerans is unique amongst mycobacteria in its tissue necrosis and local immunosuppressive effect at the site of the infection. This has been attributed to a toxin about which little is known. In this project I examined 31 strains of M. ulcerans isolated from three different continents for: 1. Pathogenicity in mouse foot-pad, which usually results in progressive swelling, except that three strains used in this project failed to do so. This observation led me to put forward the theory that the non-pathogenic form is present in the environment. The reservoir of the organism has never been found in the environment, perhaps because the work by which the organism is usually recognised is mouse pathogenicity, without which it could easily be missed. The pathogenic strains would only have to be present in small numbers to give rise to the sporadic human infections that occur. 2. The pathogenic and non-pathogenic strains were subjected to a wide range of identification methods to prove their similarities. 3. The culture filtrate of both pathogenic and non-pathogenic strains were examined in lymphocyte transformation tests (LIT) to establish whether there is a link between the suppressive effect on lymphocytes and loss of pathogenicity. 4. Attempts to isolate the suppressive factor have been carried out using HPLC and I have examined the possibilities that this suppressive factor may be phage or plasmid mediated. 5. Since BCG immunisation and anti-mycobacterial chemotherapy has proven to be ineffective in cases of M. ulcerans infection, I looked for the possibility of preventing, or delaying, the onset of the disease by vaccinating with non-virulent strains and culture filtrates.

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