An investigation of the antimycobacterial mechanisms of macrophages and potential virulence factors of mycobacteria

Polyamine oxidation and tryptophan degradation were assessed as potential oxygen-independent antimycobacterial mechanisms of guinea-pig alveolar macrophages. Products of polyamine oxidation other than hydrogen peroxide had bactericidal effects on all the tested strains of Mycobacterium tuberculosis, with the most virulent strains showing the greatest degrees of resistance to products of polyamine oxidation. However, no significant correlation was found between the susceptibility of strains to products of polyamine oxidation and their virulence in the guinea-pig. Levels of polyamine oxidase were found to be significantly higher in the lung tissue from guinea-pigs vaccinated with Mycobacterium bovis BCG compared with lung tissue from non-vaccinated animals. This indicates that polyamine oxidation may play a part in the pathogenesis of tuberculosis in the guinea-pig. Alveolar macrophages from vaccinated and non-vaccinated guinea-pigs were found to degrade tryptophan to a similar extent, which suggests that tryptophan degradation is not involved in the antimycobacterial activity of these macrophages. Investigation of the hydrophobicity of different strains of M. tuberculosis found no evidence that the hydrophobicity of a strain contributed towards its virulence in the guinea-pig. Initial analysis of culture supernatants from M. tuberculosis 12646 suggested that this organism produced a substance similar to the homoserine lactone family of autoinducers found in Gram-negative bacteria. Two fragments of DNA from Mycobacterium smegmatis were isolated which appeared to code for a mycobacterial autoinducer synthase. However, after further investigation both fragments were discounted as containing a mycobacterial autoinducer synthase. Further analysis of mycobacterial supernatants found no evidence for the presence of homoserine lactone based antoinducer.