The Mycobacterium tuberculosis complex (MTBC) evolved from an environmental organism to an obligate pathogen through a combination of genome reduction and the acquisition of new genes. Key steps in this process were acquiring the ability to grow inside host cells and the ability to transmit directly from host to host.
Data indicate that the transition from environmental organism to an obligate pathogen happened in Africa, but there is currently no consensus with respect to the timing of this event.
The MTBC comprises human-adapted and animal-adapted lineages, but the molecular basis of host preference remains largely unknown.
Among the human-adapted MTBC lineages, some occur globally and others are geographically restricted, suggesting generalist and specialist phenotypes.
Most evidence indicates that ongoing horizontal gene exchange in the MTBC is absent. As a consequence, the MTBC exhibits a clonal population structure.
Strict clonality combined with serial transmission bottlenecks leads to a reduction in MTBC genomic diversity and affects the balance between natural selection and random genetic drift.
The global epidemics of antibiotic-resistant MTBC are driven by both the de novo acquisition of resistance mutations during suboptimal patient treatment and direct transmission of resistant strains between individuals.
Tuberculosis (TB) is the number one cause of human death due to an infectious disease. The causative agents of TB are a group of closely related bacteria known as the Mycobacterium tuberculosis complex (MTBC). As the MTBC exhibits a clonal population structure with low DNA sequence diversity, methods (such as multilocus sequence typing) that are applied to more genetically diverse bacteria are uninformative, and much of the ecology and evolution of the MTBC has therefore remained unknown. Owing to recent advances in whole-genome sequencing and analyses of large collections of MTBC clinical isolates from around the world, many new insights have been gained, including a better understanding of the origin of the MTBC as an obligate pathogen and its molecular evolution and population genetic characteristics both within and between hosts, as well as many aspects related to antibiotic resistance. The purpose of this Review is to summarize these recent discoveries and discuss their relevance for developing better tools and strategies to control TB.
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The author thanks all the members of his group for the stimulating discussions over the years. Work in the author's laboratory is supported by the Swiss National Science Foundation (grants 310030_166687, IZRJZ3_164171 and IZLSZ3_170834), the European Research Council (309540-EVODRTB) and SystemsX.ch.
The author declares no competing financial interests.
- Acid-fast bacilli
Mycobacteria that have a thick, lipid-rich cell wall that retains staining despite acid treatment; hence 'acid-fast'.
- Multilocus sequence typing
A standard genotyping method based on sequence data from approximately seven housekeeping genes, which together define strain-specific sequence types.
- Professional pathogen
A pathogen with no environmental reservoir that has to cause disease to transmit from host to host.
Mycobacteria that form colonies in less than 7 days.
Mycobacteria that form colonies in more than 7 days.
- PhoPR two-component system
Mycobacterial transcription factors involved in Mycobacterium tuberculosis complex virulence.
- DosR/S/T regulon
A set of mycobacterial genes involved in latent tuberculosis infection.
- mce-associated genes
Mycobacterial genes originally identified as being involved in macrophage entry.
- ESAT6 secretion
(ESX). A protein secretion apparatus that, in the case of the Mycobacterium tuberculosis complex, exports many virulence determinants.
- Toxin–antitoxin system genes
Regulatory systems comprised of two linked genes, one encoding the toxin and the other encoding the neutralizing antitoxin.
- Smooth tubercle bacilli
(STB). Organisms that produce smooth colonies on agar plates, which is in contrast to the Mycobacterium tuberculosis complex, which produces rough colonies.
- Distributive conjugal transfer
A phage-dependent mechanism of DNA transfer between bacteria.
Bacterial variants that have incorporated DNA from other bacteria through conjugation.
- Spillover events
The occasional transfer of a particular Mycobacterium tuberculosis complex variant from its primary host species into another host species.
An alternative classification of bacterial genotypes that incorporates ecological characteristics.
Host and pathogen variants that co-occur in a given geographical setting.
Host and pathogen variants that usually occur in geographically separate settings.
- T cell epitopes
Parts of the Mycobacterium tuberculosis complex proteome (that is, peptides) that are recognized by T lymphocytes.
- Founder effects
The random introduction of a particular bacterial variant into a given setting.
Characters acquired independently by two or more bacterial variants that do not share an immediate common ancestor.
- Selective sweeps
Positive selection that leads to the fixation of a new beneficial mutation.
- Background selection
Selection against a deleterious mutation that leads to the elimination of any mutation linked to the target of selection.
- Purifying selection
Selection against detrimental mutations.
- Transmission bottlenecks
A type of population bottleneck in which only a subset of the bacterial diversity present in one host is transmitted to the next.
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Gagneux, S. Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol 16, 202–213 (2018). https://doi.org/10.1038/nrmicro.2018.8
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