TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

Bottai, Daria; Frigui, Wafa; Sayes, Fadel; Luca, Mariagrazia Di; Spadoni, Dalila; Pawlik, Alexandre; Zoppo, Marina; Orgeur, Mickael; Khanna, Varun; Hardy, David; Mangenot, Sophie; Barbe, Valérie; Médigue, Claudine; Ma, Laurence; Bouchier, Christiane; Tavanti, Arianna; Larrouy-Maumus, Gérald; Brosch, Roland

doi:10.1038/s41467-020-14508-5

Cited by 68 publications

(65 citation statements)

References 89 publications

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“…This region, which we also found intact in L8, as is the case in the 'ancestral' M. tuberculosis lineages L1 and L7, encodes members of the mycobacterial membrane protein families MmpL. Very recent findings indicate that the loss of this region in later branching MTBC strains was also associated with a gain of virulence, and the deletion of TbD1 at the origin of the 'modern' M. tuberculosis lineages L2/L3/L4 has therefore been suggested as a key driver for their global epidemic spread 54 . If true, more recently emerged or introduced cobF-and TbD1-deleted strains might conceivably have largely outcompeted L8 strains.…”

Section: Discussionmentioning

confidence: 99%

A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

et al. 2020

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The human-and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug resistant tuberculosis, representing an as-yet-unknown lineage, named Lineage 8 (L8), seemingly restricted to the African Great Lakes region. Using genome-based phylogenetic reconstruction, we show that L8 is a sister clade to the known MTBC lineages. Comparison with other complete mycobacterial genomes indicate that the divergence of L8 preceded the loss of the cobF genome region-involved in the cobalamin/vitamin B12 synthesis-and gene interruptions in a subsequent common ancestor shared by all other known MTBC lineages. This discovery further supports an East African origin for the MTBC and provides additional molecular clues on the ancestral genome reduction associated with adaptation to a pathogenic lifestyle.

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Section: Discussionmentioning

confidence: 99%

A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

et al. 2020

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“…within L4 4 – 7 , or clustered in ancestral M. tuberculosis (L1, L7–8), modern M. tuberculosis (L2–4), and M. africanum (L5–6). Modern lineages are defined by lacking the M. tuberculosis -specific deletion 1 region (TbD1) genomic segment 8 . Moreover, the MTBC includes an “animal lineage” that comprises mycobacteria that cause disease in different animals, e.g.…”

Section: Introductionmentioning

confidence: 99%

Survival of hypoxia-induced dormancy is not a common feature of all strains of the Mycobacterium tuberculosis complex

Tizzano

Dallenga

Utpatel

et al. 2021

Sci Rep

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While persistence in a dormant state is crucial for the life cycle of Mycobacterium tuberculosis, no investigation regarding dormancy survival of different strains across different lineages was performed so far. We analyzed responses to oxygen starvation and recovery in terms of growth, metabolism, and transcription. All different strains belonging to the Euro-American lineage (L4) showed similar survival and resuscitation characteristics. Different clinical isolates from the Beijing (L2), East African-Indian (L3), and Delhi/Central Asian (L1) lineage did not survive oxygen starvation. We show that dormancy survival is lineage-dependent. Recovery from O2 starvation was only observed in strains belonging to the Euro-American (L4) lineage but not in strains belonging to different lineages (L1, L2, L3). Thus, resuscitation from dormancy after oxygen starvation is not a general feature of all M. tuberculosis strains as thought before. Our findings are of key importance to understand infection dynamics of non-Euro-American vs Euro-American strains and to develop drugs targeting the dormant state.

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“…The suicide plasmid or phage-based allelic exchange approaches and ORBIT ideally result in unmarked deletions that impact the expression of a single mycobacterial gene [42]. Numerous studies reporting targeted unmarked deletions of genes in pathogenic and nonpathogenic mycobacterial species have identified roles of individual genes in various physiological and virulence processes (some exemplar publications include [50][51][52][53][54][55]). CRISPRi approaches rely on targeting the dead Cas protein (dCas) complex to prevent or reduce gene expression and can be polar on downstream genes [39].…”

Section: Exploiting the Awesome Power Of Mycobacterial Geneticsmentioning

confidence: 99%

The genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens

et al. 2021

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Mycobacterial pathogens pose a sustained threat to human health. There is a critical need for new diagnostics, therapeutics, and vaccines targeting both tuberculous and nontuberculous mycobacterial species. Understanding the basic mechanisms used by diverse mycobacterial species to cause disease will facilitate efforts to design new approaches toward detection, treatment, and prevention of mycobacterial disease. Molecular, genetic, and biochemical approaches have been widely employed to define fundamental aspects of mycobacterial physiology and virulence. The recent expansion of genetic tools in mycobacteria has further increased the accessibility of forward genetic approaches. Proteomics has also emerged as a powerful approach to further our understanding of diverse mycobacterial species. Detection of large numbers of proteins and their modifications from complex mixtures of mycobacterial proteins is now routine, with efforts of quantification of these datasets becoming more robust. In this review, we discuss the “genetic proteome,” how the power of genetics, molecular biology, and biochemistry informs and amplifies the quality of subsequent analytical approaches and maximizes the potential of hypothesis-driven mycobacterial research. Published proteomics datasets can be used for hypothesis generation and effective post hoc supplementation to experimental data. Overall, we highlight how the integration of proteomics, genetic, molecular, and biochemical approaches can be employed successfully to define fundamental aspects of mycobacterial pathobiology.

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TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

Cited by 68 publications

References 89 publications

A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

Survival of hypoxia-induced dormancy is not a common feature of all strains of the Mycobacterium tuberculosis complex

The genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens

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