The puzzle of the evolutionary natural history of tuberculosis

Abstract

Several pieces of the puzzle of the natural history of tuberculosis are assembled in this review to illustrate the potential reservoirs and sources of the Mycobacterium tuberculosis complex (MTBC) mycobacteria, their transmission to animals and humans, and their fate in populations, in a co-evolutionary perspective. Millennia-old companions of mammalian and human populations, MTBC are detected in the soil, in which they infect and survive within vegetative amoebae and cysts, except for Mycobacterium canettii. Never detected in the sphere of plants, they are transmissible by transcutaneous, digestive and respiratory routes and cause an infection of the lymphatic system with secondary dissemination in most tissues, in which they determine a specific and non-pathognomonic granulomatous inflammatory reaction; in which MTBC survives in dormant form irrespective of MTBC species and mammalian species; indicating that the current epidemiology in mammalian populations is essentially governed by the probabilities of contact between mammalian species and MTBC species. Individual variabilities in clinical expression of tuberculosis are related to MTBC species, strain and inoculum; host genetic factors; acquired modulations of the inflammatory response; and probably human microbiota. This review of the literature suggests an evolutionary natural history of telluric environmental mycobacteria, satellites of unicellular eukaryotes, transmissible to mammals via the digestive and then respiratory tracts, in which they determine a fatal contagious infection that is primarily lymphatic and a quiescence-mimicking encysted form. This review opens perspectives for microbiological and translational medical research.

Keywords: Microbiota; Mycobacterium; Mycobacterium bovis; Mycobacterium tuberculosis; natural history; sources; transmission; tuberculosis.

Fig. 1

Reservoirs of the Mycobacterium tuberculosis complex and routes of transmission to humans.

Fig. 3

Risks predisposing to the acquisition of tuberculosis and the life cycle of Mycobacterium tuberculosis in the granuloma. (a) Dormant M. tuberculosis bacilli persist in macrophages and caseum for extended periods of time. (b) When environmental conditions become conducive to reactivation, mycobacteria actively replicate leading to disruption of the integrity of the granuloma and spread to other tissues. (c) Under the action of antibiotic treatment and the immune system, initially replicating mycobacteria will be eliminated while a proportion may become dormant and persist.

Fig. 2

Species distribution of Mycobacterium tuberculosis complex in mammals; based on references [8,23,26,28,29,32,33,37,38,85].