Abstract
Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant with an inactive AnsP1 revealed that the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutant is impaired in vivo, revealing that aspartate is a primary nitrogen source required for host colonization by the tuberculosis bacillus.
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Change history
11 December 2013
In the version of this article initially published, the name of contributing author Jean-Luc Guerquin-Kern was misspelled as Jean-Luc Gerquin-Kern. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank C. Gutierrez and D. Hudrisier for carefully reading the manuscript and for their helpful suggestions. We thank L. Lepourry and F. Moreau for technical assistance with mouse infections. We thank A. Benard (IPBS, Toulouse, France) for providing mouse cells and R. Brosch (Institut Pasteur, Paris, France) for providing the I257 cosmid. We thank Y. Verkindère (YV Photographiste, Toulouse, France) for help with graphical work. We thank the PICT-IBiSA imaging facility in the Institut Curie. This work was supported by Agence Nationale de la Recherche (contracts SLC-TB and TB-HITS), the UK Medical Research Council (MC_UP_A253_1111) and the European Union Seventh Framework Programme NEWTBVAC (contract no. 241745). This work also benefited from the TRI RIO Optical Imaging Platform at the Institute of Pharmacology and Structural Biology (Genotoul, Toulouse, France) and was supported by grants from the Région Midi-Pyrénées (Contrat de Projets Etat-Région Midi-Pyrénées (CPER)), the Grand Toulouse community, the Agence pour la Recherche sur le Cancer (ARC equipement no. 8505), the Centre National de la Recherche Scientifique and the European Union–European Regional Development Fund program. A.G. and G.L.-V. hold a fellowship from the Fondation pour la Recherche Médicale. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
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A.G., J.-L.G.-K., L.P.S.d.C., Y.P. and O.N. designed the experiments. A.G., G.L.-M. and T.-D.W. performed the experiments, with technical assistance from A.P., F.L. and J.-L.G.-K. A.G., G.L.-M., T.-D.W., A.P., J.-L.G.-K., L.P.S.d.C., Y.P. and O.N. analyzed the results. A.G., G.L.-M., G.L.-V., L.P.S.d.C., Y.P. and O.N. wrote the manuscript.
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Gouzy, A., Larrouy-Maumus, G., Wu, TD. et al. Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate. Nat Chem Biol 9, 674–676 (2013). https://doi.org/10.1038/nchembio.1355
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DOI: https://doi.org/10.1038/nchembio.1355
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