Mycobacterial Evolution Intersects With Host Tolerance

Abstract

Over the past 200 years, tuberculosis (TB) has caused more deaths than any other infectious disease, likely infecting more people than it has at any other time in human history. Mycobacterium tuberculosis ( Mtb ), the etiologic agent of TB, is an obligate human pathogen that has evolved through the millennia to become an archetypal human-adapted pathogen. This review focuses on the evolutionary framework by which Mtb emerged as a specialized human pathogen and applies this perspective to the emergence of specific lineages that drive global TB burden. We consider how evolutionary pressures, including transmission dynamics, host tolerance, and human population patterns, may have shaped the evolution of diverse mycobacterial genomes.

Origin of tuberculosis in the Paleolithic predicts unprecedented population growth and female resistance

“…What is clear is the evidence for the higher dissemination ability of "modern" lineages compared with "ancient" ones 21 . The fact that the latter are restricted to specific geographical regions also points to some sort of genetic susceptibility linked to race/ethnic groups, as proposed by several authors 7,17,66 . Our model has not considered this aspect.…”

“…Portevin et al 16 compared the innate response triggered in macrophages and dendritic cells by different strains from both lineages and concluded that "ancient" ones induce a higher pro-inflammatory profile when infecting macrophages and dendritic cells. These results have been interpreted as a virulence/ immune response trade-off for "ancient" strains as bacilli are discovered early by the immune system and have less chance to progress, including extrapulmonary dissemination, which contrasts with the situation found for modern strains 17 . However, the current interpretation does not include this trade-off as this pro-inflammatory profile can, in fact, enhance the infiltration of neutrophils into Mtb-infected lesions, thus resulting in a better chance to quickly progress to active TB 18 .…”

“…(i.e., the compartment with TB-sick with the two strains). The evolution of all variables is described by Eqs (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)…”

The Evolution of Immune Sensitivity under Immunopathological and Autoimmune Costs

“…Mycobacterium tuberculosis (Mtb) has coevolved with humans for 70,000 years 28. Unlike the opportunistically parasitic and the non-pathogenic soil dwellers species of mycobacteria, Mtb has no known environmental reservoirs and does not survive outside human hosts pointing to its highly specialized nature 29. Interestingly, 90–95% of infected individuals (9 out of 10 people) are resilient or tolerant to the presence of Mtb without any disease symptoms 30.…”

Mycobacterium tuberculosisevasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system

“…Mycobacterium tuberculosis (Mtb) has become highly adapted to its human host, as it spread globally along with human migrations over tens of thousands of years (3,4). As much as one-third of the human population has been exposed to Mtb, which causes a persistent infection than can last for years, or even decades, despite a robust immune response that eradicates less pathogenic mycobacteria (5).…”