Lipids of putative relevance to virulence in Mycobacterium tuberculosis: phthiocerol dimycocerosate and the attenuation indicator lipid.

Lipid compositions of 40 patient isolates of Mycobacterium tuberculosis derived from Madras, Burma, Rangoon, and East Africa were studied, and two major populations of tubercle bacilli were distinguished. Nearly all of the strains previously designated as attenuated for the guinea pig (D. A. Mitchison) are characterized by a specific phenolic phthiocerol diester which is identified with the aglycone moieties of mycosides A and B (and probably G). This lipid (AI) was not seen in any of the more virulent strains. Thus, presence of AI may be taken as definitive for attenuation (P << 0.001). Phthiocerol dimycoserosate (DIM), a companion substance, is ubiquitous for the series of 40 strains. However, a dramatic attenuation found in a DIM-less H37Rv mutant may support a role for this substance in the virulent state. Since mycosides A, G, and B seem to be restricted to certain chromogenic and bovine species, respectively, we speculate that lysogenization or transduction of fully virulent M. tuberculosis may have provided the genetic determinants for attenuation and AI synthesis, and thus led to the two classes of tubercle bacilli.