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Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection.

TitleMycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection.
Publication TypeJournal Article
Year of Publication2014
AuthorsGouzy A, Larrouy-Maumus G, Bottai D, Levillain F, Dumas A, Wallach JB, Caire-Brandli I, de Chastellier C, Di Wu T-, Poincloux R, Brosch R, Guerquin-Kern J-L, Schnappinger D, de Carvalho LPedro Sór, Poquet Y, Neyrolles O
JournalPLoS Pathog
Volume10
Issue2
Paginatione1003928
Date Published2014 Feb
ISSN1553-7374
KeywordsAnimals, Asparagine, Chromatography, Liquid, Disease Models, Animal, Female, Flow Cytometry, Gene Knockout Techniques, Immunoblotting, Macrophages, Mass Spectrometry, Membrane Transport Proteins, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Microscopy, Immunoelectron, Mycobacterium tuberculosis, Nitrogen, Phagosomes, Stress, Physiological, Tuberculosis
Abstract

Mycobacterium tuberculosis is an intracellular pathogen. Within macrophages, M. tuberculosis thrives in a specialized membrane-bound vacuole, the phagosome, whose pH is slightly acidic, and where access to nutrients is limited. Understanding how the bacillus extracts and incorporates nutrients from its host may help develop novel strategies to combat tuberculosis. Here we show that M. tuberculosis employs the asparagine transporter AnsP2 and the secreted asparaginase AnsA to assimilate nitrogen and resist acid stress through asparagine hydrolysis and ammonia release. While the role of AnsP2 is partially spared by yet to be identified transporter(s), that of AnsA is crucial in both phagosome acidification arrest and intracellular replication, as an M. tuberculosis mutant lacking this asparaginase is ultimately attenuated in macrophages and in mice. Our study provides yet another example of the intimate link between physiology and virulence in the tubercle bacillus, and identifies a novel pathway to be targeted for therapeutic purposes.

DOI10.1371/journal.ppat.1003928
Alternate JournalPLoS Pathog
PubMed ID24586151
PubMed Central IDPMC3930563
Grant ListMC_UP_A253_1111 / / Medical Research Council / United Kingdom
MR/J006874/1 / / Medical Research Council / United Kingdom

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