{
  "abstract": "Host-directed therapies (HDTs) have acquired paramount importance for management of tuberculosis (TB). L-Serine is an important metabolite and immunomodulatory biomolecule with promising role in managing infections, and autoimmune diseases. However, the role of L-Serine as host directed therapeutic against Mycobacterium tuberculosis (M.tb) remains unexplored. Therefore, we adopted de novo-based approach and employed L-Serine and palmitoyl CoA precursors for enhancing sphingolipid in host and accessed their anti-tubercular potential. In this study, we investigated whether L-Serine could modulate the antibiotics efficacy against M.tb. L-Serine particularly in combination with palmitic acid, rifampicin and isoniazid showed enhanced intracellular bacterial clearance in a dose- and time-dependent manner in murine and human macrophages. This synergistic effect was accompanied by increased nitric oxide production and modulation of the host immune response. We identified elevated levels of pro-inflammatory cytokine TNF- and reduced anti-inflammatory IL-10 expression. Furthermore, L-Serine supplementation demonstrated antimicrobial activity in isolated primary CD14 monocytes from TB patients. Similarly, the metabolic supplementation of L-Serine in combination with isoniazid, rifampicin, and palmitic acid significantly reduced bacterial burden in the lungs and spleen, while improving tissue architecture in murine infection model. Our observations suggest that L-Serine and palmitic acid in combination with isoniazid and rifampicin contributes to the observed therapeutic effects. Collectively, this study concludes that L-Serine and palmitic acid acts as a promising host-directed therapeutic adjunct, which enhances antimicrobial immunity and potentiating antibiotic efficacy, providing a potential strategy for improving tuberculosis treatment outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Amity University Noida"
  ],
  "article_type": "Confirmatory results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "N. Sharma"
    },
    {
      "name": "R. Sharma"
    },
    {
      "name": "A. Kumar"
    },
    {
      "name": "L. K. Singh"
    },
    {
      "name": "A. Ayanur"
    },
    {
      "name": "V. Hadda"
    },
    {
      "name": "A. K. Singh"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Prakash"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fa28jrgx3x88g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.20.745965",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2.full",
  "id": "fa28jrgx3x88g",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7203973784",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fa28jrgx3x88g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "10.64898/2026.08.20.745965",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "L-Serine and Palmitoyl CoA control Mycobacterial infection by tweaking protective immune response: A potential host directed therapy for tuberculosis",
  "title_text": "L-Serine and Palmitoyl CoA control Mycobacterial infection by tweaking protective immune response: A potential host directed therapy for tuberculosis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/fa28jrgx3x88g",
  "venue": "bioRxiv",
  "versions": []
}