General Information: The Republic of Djibouti, Africa appears to be an exceptional place in terms of tuberculosis (TB) caused by Mycobacterium canettii, a highly unusual tubercle bacillus with unusual smooth colony morphology (STB) related to the M. tuberculosis complex (MTBC). M. canettii was first isolated from a 20-year-old French farmer suffering from pulmonary tuberculosis by G. Canetti in 1969. Since then, this strain has been isolated on rare occasions from patients who lived or were presumably infected in East Africa. It tends to preferentially affect children and foreigners in the Horn of Africa. M. canettii, a possible ancestor of the MTBC, is found almost exclusively in the Horn of Africa where TB is thought to have emerged about 40 000 years ago, coinciding with the expansion of human population out of Africa. The geographical restriction of M. canettii isolates and contrasting genetic diversity are characteristics compatible with a non-human reservoir. With the larger pan-genome reflecting the ancestral, wider gene pool of tubercle bacilli, their lower virulence and faster growth, especially at temperatures below 37 degrees C, plausibly reflecting broader environmental adaptability, STB strains might thus come nearer to the as-yet-unknown missing link between the obligate pathogen M. tuberculosis and environmental mycobacteria (adapted from PMIDs 20831613 and 23291586). Mycobacteria have an unusual outer membrane approximately 8nm thick, despite being considered Gram-positive. The outer membrane and the mycolic acid-arabinoglactan-peptidoglycan polymer form the cell wall, which constitutes an efficient permeability barrier in conjunction with the cell inner membrane.