Mycobacterium Tuberculosis Evolutionary Pathogenesis and its Putative Impact on Drug Development

Fabien Le Chevalier; Alessandro Cascioferro; Laleh Majlessi; Jean Louis Herrmann; Roland Brosch


Future Microbiol. 2014;9(8):969-985. 

In This Article


Mycobacteria are very widespread in different environments, including soil and aqueous microbiota, where contact with other microorganisms is dense. From an evolutionary perspective, it seems plausible that factors that contribute today to mycobacterial pathogenesis might have evolved during the long interplay of mycobacteria with other microorganisms, including protozoa. Today's virulence factors might constitute ancestral invasion and defense mechanisms that were transformed by pathogenic mycobacteria into tools that are now used for intracellular survival in cells of vertebrate hosts. These genes involved in pathogenicity, together with the core genes involved in the essential functions of mycobacteria, may constitute promising new targets for the development of specific antimycobacterial molecules and compounds that can act in synergy with other available strategies. Besides the treatment regimens already in place or in development, high-content screening approaches of compounds and/or cellular particularities[43,114] that can simultaneously evaluate the viability of host phagocytes and the bacterial growth characteristics thus show great promise for the identification of appropriate candidates. Comparative genome information from various mycobacterial species and insights into the evolutionary traits of the concerned genes and gene products will be of further help for validation purposes.