{
  "abstract": "Tuberculosis remains the leading cause of death from a single infectious agent, and rising multi-drug resistance in Mycobacterium tuberculosis (Mtb) underscores the urgent need for new antibiotics. Here, we characterize BVL3572S, a hydroxamic acid-containing compound that is bactericidal against Mtb. The primary targets of BVL3572S are the pyridoxal phosphate (PLP; active form of vitamin B6)-dependent aminotransferases HisC (Rv1600) and AlaA (Rv0337c; formerly AspC), simultaneously impacting L-histidine and L-alanine biosynthesis. X-ray crystallography revealed a covalent PLP-BVL3572S adduct within the HisC active site. The formation of the adduct followed by its release suggests a futile cycle that depletes PLP. Consistently, isotopic labeling revealed widespread perturbation of amino acid biosynthesis. CRISPRi and Tn-seq analyses additionally indicated disruptions in central metabolism, cell envelope integrity, and redox balance. BVL3572S displayed strong synergy with the antitubercular drug D-cycloserine. Collectively, our findings establish BVL3572S as a promising lead compound acting through a previously unexploited, multitarget mechanism.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "name": "Zainab Edoo"
    },
    {
      "name": "Astrid Lenne-Delmotte"
    },
    {
      "name": "Camille Grosse"
    },
    {
      "name": "Marie Devaere"
    },
    {
      "name": "Marion Michel"
    },
    {
      "name": "Guillaume Caron"
    },
    {
      "name": "Ernesto Anoz-Carbonell"
    },
    {
      "name": "Kamel Djaout"
    },
    {
      "name": "Rosangela Frita"
    },
    {
      "name": "Cyril Gaudin"
    },
    {
      "name": "Line Hofmann"
    },
    {
      "name": "Sophie Lecher"
    },
    {
      "name": "Véronique Megalizzi"
    },
    {
      "name": "Alessia Michelotti"
    },
    {
      "name": "David Rengel"
    },
    {
      "name": "Pauline Rouan"
    },
    {
      "name": "Stephanie Slupek"
    },
    {
      "name": "Lina Tawk"
    },
    {
      "name": "Rudy Antoine"
    },
    {
      "name": "Hanna Kulyk"
    },
    {
      "name": "Glenn Dale"
    },
    {
      "name": "Christophe Guilhot"
    },
    {
      "name": "Nicolas Willand"
    },
    {
      "name": "Guy Lippens"
    },
    {
      "name": "René Wintjens"
    },
    {
      "name": "Alain Baulard"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1k1ctrzrx53yz.bib",
  "cited_by": 0,
  "doi": "10.1016/j.chembiol.2026.07.008",
  "fulltext_url": null,
  "id": "1k1ctrzrx53yz",
  "issns": [
    "2451-9456",
    "2451-9448"
  ],
  "landing_url": "https://hal.science/hal-05797964v1",
  "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"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "1.sdv.mp"
    ],
    [
      "hal",
      "1.sdv.sp"
    ],
    [
      "hal",
      "2.sdv.mhep.mi"
    ],
    [
      "hal",
      "2.sdv.mhep.psr"
    ],
    [
      "hal",
      "2.sdv.mp.bac"
    ],
    [
      "hal",
      "2.sdv.sp.pharma"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7202166805",
  "pdf_url": "https://hal.science/hal-05797964/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-11",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/1k1ctrzrx53yz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "hal-05797964",
      "source": "hal",
      "url": "https://hal.science/hal-05797964v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.mi",
      "subfield": "infectious-disease"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.sp",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "BVL3572S inhibits HisC and AlaA, exploiting vitamin B6 dependency to kill Mycobacterium tuberculosis",
  "title_text": "BVL3572S inhibits HisC and AlaA, exploiting vitamin B6 dependency to kill Mycobacterium tuberculosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/1k1ctrzrx53yz",
  "venue": "Cell Chemical Biology",
  "versions": []
}