Skip to Main content Skip to Navigation
Journal articles

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

Daria Bottai 1, * Wafa Frigui 2 Fadel Sayes 2 Mariagrazia Di Luca 1 Dalila Spadoni 1 Alexandre Pawlik 2 Marina Zoppo 1 Mickael Orgeur 2 Varun Khanna 2 David Hardy 3 Sophie Mangenot 4, 5 Valérie Barbe 4, 5 Claudine Médigue 6 Laurence Ma 7 Christiane Bouchier 7 Arianna Tavanti 1 Gerald Larrouy-Maumus 8 Roland Brosch 2, *
* Corresponding author
1 University of Pisa - Università di Pisa
2 Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics
3 Neuropathologie expérimentale - Experimental neuropathology
4 GENOSCOPE - Genoscope - Centre national de séquençage [Evry]
5 UEVE - Université d'Évry-Val-d'Essonne
6 LABGeM - Analyse Bio-Informatique pour la Génomique et le Métabolisme
UMR 8030 - Génomique métabolique : DRF/JACOB
7 Génomique (Plate-Forme) - Genomics Platform
8 Imperial College London
Abstract : Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss of the MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted "modern" lineages are responsible for globally-spread tuberculosis epidemics, whereas TbD1-intact "ancestral" lineages tend to be restricted to specific geographical areas, such as South India and South East Asia (L1) or East Africa (L7). By constructing and characterizing a panel of recombinant TbD1-knock-in and knock-out strains and comparison with clinical isolates, here we show that deletion of TbD1 confers to Mtb a significant increase in resistance to oxidative stress and hypoxia, which correlates with enhanced virulence in selected cellular, guinea pig and C3HeB/FeJ mouse infection models, the latter two mirroring in part the development of hypoxic granulomas in human disease progression. Our results suggest that loss of TbD1 at the origin of the L2/L3/L4 Mtb lineages was a key driver for their global epidemic spread and outstanding evolutionary success.
Document type :
Journal articles
Complete list of metadata

Cited literature [88 references]  Display  Hide  Download
https://hal-pasteur.archives-ouvertes.fr/pasteur-02473990
Contributor : Laurence Langlais Connect in order to contact the contributor
Submitted on : Tuesday, February 11, 2020 - 10:11:39 AM
Last modification on : Friday, August 20, 2021 - 3:26:57 AM
Long-term archiving on: : Tuesday, May 12, 2020 - 1:55:02 PM

File

Vignette du document
s41467-020-14508-5.pdf
Publication funded by an institution

Licence

Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

PASTEUR | CEA | JACOB | CNRS | CEA-DRF | UNIV-PARIS | GS-BIOSPHERA | GENOSCOPE | GS-LIFE-SCIENCES-HEALTH | CEA-UPSAY | UNIV-EVRY

Citation

Daria Bottai, Wafa Frigui, Fadel Sayes, Mariagrazia Di Luca, Dalila Spadoni, et al.. TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.684. ⟨10.1038/s41467-020-14508-5⟩. ⟨pasteur-02473990⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

980

Files downloads

1101