L-Serine and Palmitoyl CoA control Mycobacterial infection by tweaking protective immune response: A potential host directed therapy for tuberculosis
- 1Amity University Noida
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.
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BibTeX
@misc{sharma2026lserine,
title = {{L-Serine and Palmitoyl CoA control Mycobacterial infection by tweaking protective immune response: A potential host directed therapy for tuberculosis}},
author = {N. Sharma and R. Sharma and A. Kumar and L. K. Singh and A. Ayanur and V. Hadda and A. K. Singh and H. Prakash},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.20.745965},
url = {https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - L-Serine and Palmitoyl CoA control Mycobacterial infection by tweaking protective immune response: A potential host directed therapy for tuberculosis
AU - N. Sharma
AU - R. Sharma
AU - A. Kumar
AU - L. K. Singh
AU - A. Ayanur
AU - V. Hadda
AU - A. K. Singh
AU - H. Prakash
PY - 2026
DA - 2026/08/20
PB - bioRxiv
DO - 10.64898/2026.08.20.745965
UR - https://www.biorxiv.org/content/10.64898/2026.08.20.745965v2
AB - 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.
ER -