A glimpse into the past and predictions for the future: the molecular evolution of the tuberculosis agent

Abstract

SummaryRecent advances in genomics and molecular biology are providing an excellent opportunity to get a glimpse into the past, to examine the present, and to predict the future evolution of pathogenic mycobacteria, and in particular that of Mycobacterium tuberculosis, the agent of human tuberculosis. The recent availability of genome sequences of several Mycobacterium canettii strains, representing evolutionary early-branching tubercle bacilli, has allowed the genomic and molecular features of the putative ancestor of the M. tuberculosis complex (MTBC) to be reconstituted. Analyses have identified extensive lateral gene transfer and recombination events in M. canettii and/or the MTBC, leading to suggestions of a past environmental reservoir where the ancestor(s) of the tubercle bacilli might have adapted to an intracellular lifestyle. The daily increases in M. tuberculosis genome data and the remaining urgent Public Health problem of tuberculosis make it more important than ever to try and understand the origins and the future evolution of the MTBC. Here we critically discuss a series of questions on gene-loss, acquisition, recombination, mutation and conservation that have recently arisen and which are key to better understand the outstanding evolutionary success of one of the most widespread and most deadly bacterial pathogens in the history of humankind.

BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex–Specific Lipopeptides in Guinea Pigs

“…5A). By contrast, the responses to CME obtained from more distantly related MTC mycobacteria such as M. canettii (28), which has been suggested as the last common ancestor of the MTC strains (29), and M. marinum, which represents the most closely related nontuberculous mycobacterial species, exceeded the 20% threshold nonsignificantly, and CMEs produced from other non-MTC mycobacteria did not elicit a response at all (Fig. 5B).…”

Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

“…Their mode of transmission seems to be different to M. tuberculosis because no human-to-human transmission of M. canettii strains was yet reported (18,35,37). M. canettii strains might have a yet-unknown, possibly aquatic, environmental reservoir where different strains can get in frequent direct contact, thereby enhancing the possibilities of HGT (10,17,38,39). In a similar scenario, one could also imagine that M. tuberculosis and the MTBC originally emerged from an M. canettii-like strain pool and subsequently adapted to their respective host(s), followed by clonal expansion (21,39) (Fig.…”

“…specific to M. canettii strain K (STB-K) (10), as well as genes that are specifically shared by a whole group of strains, such as the pe_pgrs33 (rv1818) gene of MTBC members (10,39). Whereas the M. canettii strain-specific genes might be the result of recent HGT among these strains and other environmental bacteria, the supposed transfer of pe_pgrs33 to the common ancestor of the MTBC might represent a more ancient occurrence, at the beginning of the clonal emergence of the MTBC from M. canettii-like generalist bacteria toward pathogens of mammalian hosts.…”

Substantial molecular evolution and mutation rates in prolonged latent Mycobacterium tuberculosis infection in humans

“…It is estimated that one-third of the global human population is infected with latent Mtb, constituting a vast disease reservoir. As a genetically monomorphic organism (Boritsch et al, 2014;Eldholm and Balloux, 2016), the adaptational potential of Mtb, i.e. its capacity to genetically adapt to the host immune system or drug interventions, is tightly linked to its in vivo mutation rate (Eldholm and Balloux, 2016;Ford et al, 2013;Takiff and Feo, 2015) and the type of accumulated mutations (synonymous vs non-synonymous).…”