Title :

Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation

Author(s) :

Levillain, Florence [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]
Poquet, Yannick [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]
Mallet, Ludovic [Auteur]
Unité de Mathématiques et Informatique Appliquées de Toulouse [MIAT INRA]
Mazeres, Serge [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]
Marceau, Michael [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Brosch, Roland [Auteur]
Pathogénomique mycobactérienne intégrée
Bange, Franz-Christoph [Auteur]
Hannover Medical School [Hannover] [MHH]
Supply, Philip [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Magalon, Axel [Auteur]
Laboratoire de chimie bactérienne [LCB]
Neyrolles, Olivier [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]

Journal title :

PLoS pathogens

Pages :

e1006752

Publisher :

Public Library of Science

Publication date :

2017

ISSN :

1553-7366

English keyword(s) :

Fungal evolution
Gene expression
Mycobacterium tuberculosis
Nitrates
Hypoxia
Genetic loci
Sequence alignment
Horizontal gene transfer

HAL domain(s) :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie

English abstract : [en]

The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, to persist for long periods of time in lung hypoxic lesions chiefly contributes to the global burden of latent TB. We and others previously ...
Show more >The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, to persist for long periods of time in lung hypoxic lesions chiefly contributes to the global burden of latent TB. We and others previously reported that the M. tuberculosis ancestor underwent massive episodes of horizontal gene transfer (HGT), mostly from environmental species. Here, we sought to explore whether such ancient HGT played a part in M. tuberculosis evolution towards pathogenicity. We were interested by a HGT-acquired M. tuberculosis-specific gene set, namely moaA1-D1, which is involved in the biosynthesis of the molybdenum cofactor. Horizontal acquisition of this gene set was striking because homologues of these moa genes are present all across the Mycobacterium genus, including in M. tuberculosis. Here, we discovered that, unlike their paralogues, the moaA1-D1 genes are strongly induced under hypoxia. In vitro, a M. tuberculosis moaA1-D1-null mutant has an impaired ability to respire nitrate, to enter dormancy and to survive in oxygen-limiting conditions. Conversely, heterologous expression of moaA1-D1 in the phylogenetically closest non-TB mycobacterium, Mycobacterium kansasii, which lacks these genes, improves its capacity to respire nitrate and grants it with a marked ability to survive oxygen depletion. In vivo, the M. tuberculosis moaA1-D1-null mutant shows impaired survival in hypoxic granulomas in C3HeB/FeJ mice, but not in normoxic lesions in C57BL/6 animals. Collectively, our results identify a novel pathway required for M. tuberculosis resistance to host-imposed stress, namely hypoxia, and provide evidence that ancient HGT bolstered M. tuberculosis evolution from an environmental species towards a pervasive human-adapted pathogen.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Les transferts horizontaux sont-ils liés à la virulence du bacille tuberculeux : Recherche de nouvelles cibles médicamenteuses pour vaincre la tuberculose
Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL