Comparative Mycobacteriology of the Mycobacterium tuberculosis complex

Abstract

The Mycobacterium tuberculosis complex (MTBC) is a group of highly genetically related pathogens that cause tuberculosis (TB) in mammalian species. However, the very name of the complex underlines the fact that our knowledge of these pathogens is dominated by studies on the human pathogen, M. tuberculosis. Of course this is entirely justified; M. tuberculosis is a major global pathogen that exacts a horrendous burden in terms of mortality and morbidity so it is appropriate that it is the cornerstone of the complex. In the same way as M. tuberculosis is the best studied human tubercle bacillus, our knowledge of the animal-adapted strains has been dominated by studies with M. bovis. Again, given the economic importance of bovine TB and the potential for zoonotic transmission to humans, this is entirely expected. However, taking M. tuberculosis and M. bovis as the human- and animal-adapted poles¿of the complex, our focus on these pathogens to the exclusion of others members has restricted, and potentially skewed, our understanding of diversity, virulence and host adaptation within the MTBC. Referring to Theobald Smith above, have we really exploited comparative studies of the tubercle bacilli to their full potential, or have we regarded the MTBC as merely M. tuberculosis plus some animal pathogens of lesser import? Herein we discuss our current understanding of the make-up of the MTBC, focussing on comparisons of M. tuberculosis and M. bovis as the exemplar human- and animal-adapted strains, and look to what studies of these pathogens can teach us about the evolution of the MTBC specifically and the emergence of host adaptation in pathogens in general. We also speculate on how our current focus on M. tuberculosis and M. bovis may have hindered our appreciation of fundamental concepts such as virulence, evolution and host adaptation of the tubercle bacilli.