ArticleNature communications2023
Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Host-directed treatments for tuberculous meningitis utilizing a multi-platform approach across mouse and human models.Nature communications · 2026Article
- Elimination of senescent cells with senolytic drugs as adjunctive host-directed therapy reduces tuberculosis progression in mice.Nature communications · 2026Article
- STING-ERO1 signaling exacerbates PARylation-mediated parthanatos in sepsis.Cell communication and signaling : CCS · 2026Article
- Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.Research square · 2026Article
- Discovery of the PARP1 Inhibitors from Natural Compounds Using Structure-Based Virtual Screening and Bioactivity Evaluation.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Article
- Review
- Effects of adenosine triphosphate, thiamine pyrophosphate, melatonin, and liv-52 on subacute pyrazinamide proliferation hepatotoxicity in rats.BMC pharmacology & toxicology · 2025Article
- Multi-Omics Integration Reveals Mitochondrial Gene Regulation as a Determinant of Tuberculosis Susceptibility: A Mendelian Randomization Approach.Biomedicines · 2025Article
- Cardiovascular Involvement in Tuberculosis Patients Treated in Southern Africa.JACC. Advances · 2025Article
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Colon-Targeted Poly(ADP-ribose) Polymerase Inhibitors Synergize Therapeutic Effects of Mesalazine Against Rat Colitis Induced by 2,4-Dinitrobenzenesulfonic Acid.Pharmaceutics · 2024Article
- Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis.Biomolecules · 2024Review
- Expanding the Perspective on PARP1 and Its Inhibitors in Cancer Therapy: From DNA Damage Repair to Immunomodulation.Biomedicines · 2024Review
- Clinical Significance of Preoperative Pyrazinamide-Containing Therapy in Tuberculous Constrictive Pericarditis.Infection and drug resistance · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The antibiotic pyrazinamide (PZA) is a cornerstone of tuberculosis (TB) therapy that shortens treatment durations by several months despite being only weakly bactericidal. Intriguingly, PZA is also an anti-inflammatory molecule shown to specifically reduce inflammatory cytokine signaling and lesion activity in TB patients. However, the target and clinical importance of PZA's host-directed activity during TB therapy remain unclear. Here, we identify the host enzyme Poly(ADP-ribose) Polymerase 1 (PARP1), a pro-inflammatory master regulator strongly activated in TB, as a functionally relevant host target of PZA. We show that PZA inhibits PARP1 enzymatic activity in macrophages and in mice where it reverses TB-induced PARP1 activity in lungs to uninfected levels. Utilizing a PZA-resistant mutant, we demonstrate that PZA's immune-modulatory effects are PARP1-dependent but independent of its bactericidal activity. Importantly, PZA's bactericidal efficacy is impaired in PARP1-deficient mice, suggesting that immune modulation may be an integral component of PZA's antitubercular activity. In addition, adjunctive PARP1 inhibition dramatically reduces inflammation and lesion size in mice and may be a means to reduce lung damage and shorten TB treatment duration. Together, these findings provide insight into PZA's mechanism of action and the therapeutic potential of PARP1 inhibition in the treatment of TB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.