{
  "abstract": "Copper is recognized as a host-derived cue encountered by Mycobacterium tuberculosis and other microbes during infections, yet the magnitude, intracellular distribution, and physiological consequences of this exposure remain incompletely understood. Here, we combined high-resolution imaging, transcriptomic profiling, intracellular reporter assays, and mouse infection models to define how M. tuberculosis responds to physiologically relevant copper levels during infection. NanoSIMS analysis showed that copper reaches intracellular bacilli and accumulates in discrete phosphorus-rich foci in bacteria. Exposure to physiological copper concentrations in vitro triggered a highly specific transcriptional response dominated by the copper-inducible CsoR and RicR regulons. The RicR-regulated cysK2 gene, encoding the (S-sulfo)cysteine synthase CysK2, was one of the most strongly induced loci. In infected macrophages, cysK2 expression was modulated by extracellular copper availability, host copper transport pathways, and hypoxia. In vivo, the H37Rv cysK2-deficient mutant showed reduced long-term persistence in mice and a shift toward a more oxidized redox potential. Together, these findings identify CysK2 as a copper-responsive effector linking host-derived copper sensing to redox homeostasis and contributing to long-term persistence during infection.\n\nIMPORTANCE: Successful infection by Mycobacterium tuberculosis depends on its ability to detect and adapt to host-imposed changes in the phagosomal environment. Our work shows that copper contributes to this adaptation not simply by imposing toxicity, but by triggering a response that helps sustain bacterial fitness within host cells. We identify CysK2 as a key component of this response, linking copper sensing to sulfur metabolism, redox balance, and persistence during infection. These findings shift the view of copper from a purely antimicrobial factor to a host-derived environmental signal that remodels M. tuberculosis physiology, and they uncover a new mechanism by which the pathogen maintains intracellular survival.",
  "abstract_shown": true,
  "affiliations": [
    "Univ Toulouse, CNRS, IPBS, Toulouse, France",
    "Institut Curie, CNRS Unité d'Appui et de Recherche UAR2016, Inserm Unité de Service US43, Université Paris-Saclay, Multimodal Imaging Center, Orsay, France",
    "Centre for Bacterial Resistance Biology, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, United Kingdom"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wendy Le Mouëllic",
      "orcid": "0009-0008-3251-036X"
    },
    {
      "affs": [
        0
      ],
      "name": "Florence Levillain"
    },
    {
      "affs": [
        1
      ],
      "name": "Ting-Di Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Gérald Larrouy-Maumus"
    },
    {
      "affs": [
        0
      ],
      "name": "Frédéric Lagarrigue"
    },
    {
      "affs": [
        0
      ],
      "name": "Edith Vidal"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoann Rombouts"
    },
    {
      "affs": [
        0
      ],
      "name": "Yannick Poquet",
      "orcid": "0009-0002-6430-6095"
    },
    {
      "affs": [
        0
      ],
      "name": "Olivier Neyrolles",
      "orcid": "0000-0003-0047-5885"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/069ks4p8jqmkd.bib",
  "cited_by": 0,
  "doi": "10.1128/mbio.00816-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712839/",
  "id": "069ks4p8jqmkd",
  "issns": [
    "2150-7511"
  ],
  "landing_url": "https://doi.org/10.1128/mbio.00816-26",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7211965098",
  "pdf_url": null,
  "pmcid": "PMC13712839",
  "pmid": "42708649",
  "published": "2026-09-08",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/069ks4p8jqmkd.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:20Z",
      "native_id": "PMC13712839",
      "source": "pmc",
      "url": "https://doi.org/10.1128/mbio.00816-26"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "CysK2 couples copper sensing to redox adaptation in Mycobacterium tuberculosis",
  "title_text": "CysK2 couples copper sensing to redox adaptation in Mycobacterium tuberculosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:20Z",
  "url": "https://research.draconitic.com/paper/069ks4p8jqmkd",
  "venue": "mBio",
  "versions": []
}