The causative organism of tuberculosis, the tubercle bacillus, was isolated and described by Robert Koch in 1882 (Figure 56.1). It was subsequently included in the genus Mycobacterium and named Mycobacterium tuberculosis. A closely related species isolated from cattle but also able to cause human tuberculosis is termed M. bovis and strains with rather variable properties principally encountered in Equatorial Africa are collectively termed M. africanum. These species are included in the Mycobacterium tuberculosis complex, the members of which are obligate pathogens of mammals and are thus distinct from almost all other mycobacteria, of which there are over 100 officially recognized and named species. Other named species within this complex are M. canetti, a rarely encountered strain that produces smooth colonies on culture medium, M. microti, a rare cause of tuberculosis in small mammals but of very low virulence in humans, M. pinnepedii, the cause of tuberculosis in seals and seal handlers and M. caprae, a variant of M. bovis isolated from goats and, occasionally, humans. Although differing in several respects, especially in their host ranges, all species in the Mycobacterium tuberculosis complex are very closely related, differing in their genomic DNA sequence by less than 0.1% and are therefore really variants of a single species. The variants have arisen more by devolution than evolution, principally by the loss of units of DNA termed Regions of Difference (RD) from a common progenitor type, ‘M. prototuberculosis', which was probably very similar to M. canetti.^[1]

Figure 56.1  Professor Robert Koch, discoverer of Mycobacterium tuberculosis.

Until recently, it was thought that strains of M. tuberculosis were very similar in their pathogenicity and virulence, but ‘fingerprinting’ (p. 992) has revealed several lineages, superfamilies or clades (e.g. Haarlem, Beijing, Somali, Indo-Oceanic, Central Asian) which, certainly in the mouse and probably in humans, differ in their virulence and growth rate in macrophages, the immune responses required for overcoming the disease, and the ability of BCG vaccination to afford protection against them. It has been postulated that the various lineages have arisen by adaptation to the local human population, in which they may cause more severe disease than in genetically less related populations.^[2] One lineage, though, the Beijing (or W/Beijing) lineage, is a cause for concern as it is spreading worldwide and it appears to be more virulent than other lineages and less likely to lose some virulence on mutation to multi-drug resistance.^[3,4]

Tubercle bacilli are aerobic, non-motile, non-sporing, usually slightly curved rods 2–4 μm in length and 0.3–0.5 μm in diameter. In common with other mycobacteria, they retain arylmethane dyes on treatment with mineral acids, a property termed acidfastness. This property is widely used to detect mycobacteria in clinical specimens by light microscopy after staining by the Ziehl–Neelsen method (Figure 56.2) or by fluorescence microscopy. Tubercle bacilli grow slowly on conventional solid culture media and colonies take from 2 to 6 weeks to appear. More rapid automated culture systems and nucleic acid-based detection systems are now available (see p. 998).

Figure 56.2  (A) Ziehl–Neelsen staining of a sputum sample and (B) a bronchoalveolar lavage washing showing acid-fast bacilli.