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A deeper understanding of\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    metabolism could uncover specific vulnerabilities and inform the development of new treatments. Sulfur, essential for bacterial growth and survival, fuels key pathways including redox buffering and coenzyme production. Although previous studies suggest that\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    utilizes various substrates to meet its sulfur requirements, the primary sources of sulfur exploited during in vivo infection remain unclear. Here, we reveal that\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    acquires inorganic sulfate through the SubI-CysTWA transporter during macrophage infection. Using nanoSIMS (high spatial resolution Secondary Ion Mass Spectrometry) analysis, we observed significant sulfate-derived\n                    <jats:sup>33<\/jats:sup>\n                    S enrichment in intracellular bacteria, correlating with metabolic activity. Deletion of\n                    <jats:italic toggle=\"yes\">subI<\/jats:italic>\n                    abolished sulfate uptake, impairing bacterial growth in vitro and reducing\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    survival in murine macrophages and lungs of infected mice. Finally, our data demonstrate that sulfate acquisition is essential for maintaining mycobacterial redox balance and resisting nitrosative stress in vitro and in vivo. Thus, unlike many intracellular pathogens,\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    depends on an energetically costly inorganic sulfate assimilation pathway to survive in the nutrient-limited host environment. These findings challenge prior assumptions that organic reduced sulfur sources, such as methionine, fuel\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    sulfur metabolism during infection. Since animal cells lack a sulfate assimilation pathway, uncovering the critical role of SubI-CysTWA-mediated sulfate import in\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    pathogenesis highlights this pathway as a promising pathogen-specific therapeutic target. Targeting this system could either directly impair\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    survival during infection or sensitize bacilli to antibiotic-induced oxidative stress by disrupting redox homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2503966122","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T19:00:41Z","timestamp":1758567641000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Inorganic sulfate is critical for\n                    <i>Mycobacterium tuberculosis<\/i>\n                    lung tissue colonization and redox balance"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3251-036X","authenticated-orcid":false,"given":"Wendy","family":"Le Mou\u00ebllic","sequence":"first","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale, Universit\u00e9 de Toulouse, CNRS, Universit\u00e9 Paul Sabatier","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Levillain","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale, Universit\u00e9 de Toulouse, CNRS, Universit\u00e9 Paul Sabatier","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Institut Curie, Paris Sciences et Lettres University, Universit\u00e9 Paris-Saclay, CNRS Unit\u00e9 d'Appui et de Recherche 2016, Inserm US43, Multimodal Imaging Center","place":["Orsay, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9232-7773","authenticated-orcid":false,"given":"Maxime","family":"Caouaille","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale, Universit\u00e9 de Toulouse, CNRS, Universit\u00e9 Paul Sabatier","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-561X","authenticated-orcid":false,"given":"Philippe","family":"Bousso","sequence":"additional","affiliation":[{"name":"Dynamics of Immune Responses Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Poquet","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale, Universit\u00e9 de Toulouse, CNRS, Universit\u00e9 Paul Sabatier","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-5885","authenticated-orcid":false,"given":"Olivier","family":"Neyrolles","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et de Biologie 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