Role of lipid content and hydrogen peroxide susceptibility in determining the guinea-pig virulence of Mycobacterium tuberculosis.

Among isoniazid-sensitive strains of Mycobacterium tuberculosis, strong associations were found in 56 strains of phage type A and I from India, Burma and East Africa between attenuation in the guinea-pig, a low content of strongly acidic (SAL) and sulphatide (SL) lipids, the presence of the attenuation indicator (AI) lipid and phage type I, suggesting that lipid content might mediate attenuation. However, 22 strains of phage type B and I from Iran and Britain also had low contents of SAL and SL but were highly virulent. Although the finding of a strong association in all 78 strains between attenuation and H2O2 susceptibility in vitro supports other evidence that attenuation is often due to increased susceptibility to H2O2 secreted by macrophages, an alternative mediator of virulence probably exists since 8 of the strains were attenuated and also resistant to H2O2. Identification of South Indian attenuated strains for epidemiological purposes by in vitro tests would be best achieved by the presence of AI, H2O2 susceptibility and, if the strains originated in or near India, by phage type I.