{
  "abstract": "To sustain the anti-tuberculosis drug development pipeline, novel antibiotics must be developed both as standalone agents and as components of future combination regimens. To this end, tricyclic-spirolactams (TriSLa)-based inhibitors of mycobacterial type II NADH dehydrogenase (Ndh-2) represent a promising novel class of antibiotics, though activity is carbon source dependent. Initial studies established an enhanced understanding of the impact of TriSLa on mycobacteria using metabolomics and transcriptomics. Then, CRISPRi chemical-genetics and extensive in vitro TriSLa-combination studies showed that Ndh-2 inhibition resulted in rendering other components of the electron transport chain vulnerable, even in conditions when TriSLa was inactive alone. Finally, identified in vitro synergistic TriSLa-antibiotic combinations were validated to also give modestly improved in vivo efficacy. Together, this work expands our understanding of how Ndh-2 inhibition impacts bacterial physiology and reveals how it sensitizes the bacterium to electron transport chain inhibitors, providing a foundation for future TriSLa-based combination regimens.",
  "abstract_shown": true,
  "affiliations": [
    "University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille (CIIL), Lille, France",
    "Centre d'Immunologie et des Maladies Infectieuses, CIMI, Sorbonne Université, CNRS, Inserm, Paris, France",
    "University Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems, Lille, France",
    "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore",
    "Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, AP-HP, Sorbonne Université, Paris, France",
    "Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore",
    "National Center for Infectious Diseases (NCID), Singapore, Singapore",
    "Radboud Institute for Biological and Environmental Sciences, Radboud University, Nijmegen, the Netherlands"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vien Q. T. Ho",
      "orcid": "0000-0001-9405-7195"
    },
    {
      "affs": [
        1
      ],
      "name": "Vincent Fontaine"
    },
    {
      "affs": [
        0
      ],
      "name": "Ernesto Anoz-Carbonell",
      "orcid": "0000-0002-6649-9153"
    },
    {
      "affs": [
        0
      ],
      "name": "Kamel Djaout",
      "orcid": "0000-0003-1218-8031"
    },
    {
      "affs": [
        2
      ],
      "name": "Clement Vigier"
    },
    {
      "affs": [
        2
      ],
      "name": "Leo Faion",
      "orcid": "0000-0002-6439-9861"
    },
    {
      "affs": [
        3
      ],
      "name": "Samsher Singh",
      "orcid": "0000-0001-7075-931X"
    },
    {
      "affs": [
        0
      ],
      "name": "Sushovan Dam"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonathan Chatagnon",
      "orcid": "0000-0003-0496-8548"
    },
    {
      "affs": [
        0
      ],
      "name": "Stéphanie Slupek"
    },
    {
      "affs": [
        0
      ],
      "name": "Rudy Antoine",
      "orcid": "0000-0002-7369-0626"
    },
    {
      "affs": [
        1
      ],
      "name": "Aurélie Chauffour",
      "orcid": "0000-0002-8846-5069"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Alexandra Aubry"
    },
    {
      "affs": [
        2
      ],
      "name": "Benoit Deprez",
      "orcid": "0000-0002-2777-4538"
    },
    {
      "affs": [
        3,
        5,
        6
      ],
      "name": "Kevin Pethe",
      "orcid": "0000-0003-0916-8873"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Nicolas Veziris",
      "orcid": "0000-0001-5660-6544"
    },
    {
      "affs": [
        2
      ],
      "name": "Nicolas Willand",
      "orcid": "0000-0002-0784-0462"
    },
    {
      "affs": [
        7
      ],
      "name": "Robert Jansen",
      "orcid": "0000-0001-9612-2798"
    },
    {
      "affs": [
        2
      ],
      "name": "Baptiste Villemagne",
      "orcid": "0000-0002-8416-5253"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruben C. Hartkoorn",
      "orcid": "0000-0001-7315-1553"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9ewg4wq9awpwx.bib",
  "cited_by": 0,
  "doi": "10.1128/aac.00756-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731233/",
  "id": "9ewg4wq9awpwx",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://hal.science/hal-05780392v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "heading",
      "Experimental Therapeutics"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7214194555",
  "pdf_url": null,
  "pmcid": "PMC13731233",
  "pmid": "42782165",
  "published": "2026-09-24",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/9ewg4wq9awpwx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:48Z",
      "native_id": "hal-05780392",
      "source": "hal",
      "url": "https://hal.science/hal-05780392v1"
    },
    {
      "first_seen": "2026-11-08T12:21:28Z",
      "native_id": "PMC13731233",
      "source": "pmc",
      "url": "https://doi.org/10.1128/aac.00756-26"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Inhibition of type II NADH dehydrogenase in Mycobacterium tuberculosis reveals collateral vulnerability in the electron transport chain",
  "title_text": "Inhibition of type II NADH dehydrogenase in Mycobacterium tuberculosis reveals collateral vulnerability in the electron transport chain",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:28Z",
  "url": "https://research.draconitic.com/paper/9ewg4wq9awpwx",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}