ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2023
Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis.
Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Mitochondrial STAT3-mediated suppression of apoptosis constrains antimycobacterial immunity.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the circRNA-Mediated ceRNA regulatory network in dendritic cells during H37Ra and BCG infection.Frontiers in molecular biosciences · 2026Article
- NR4A nuclear receptor expression in human macrophages mediates apoptosis and controls Mycobacterium tuberculosis growth.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Advances in host-directed therapy for tuberculosis and HIV coinfection: enhancing immune responses.Trends in microbiology · 2025Review
- Timing matters in macrophage/CD4+ T cell interactions: an agent-based model comparingmSystems · 2025Article
- Leveraging insights from cancer to improve tuberculosis therapy.Trends in molecular medicine · 2025Article
- Dysregulation of the JNK signaling pathway in tuberculosis: mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Efficacy and Possible Mechanism(s) of Action of Gallium Tetraphenylporphyrin Nanoparticles against HIV-TB Coinfection in anACS infectious diseases · 2024Article
- Synthesis, Anti-Cancer Activity, Cell Cycle Arrest, Apoptosis Induction, and Docking Study of Fused Benzo[Molecules (Basel, Switzerland) · 2024Article
- Proapoptotic Bcl-2 inhibitor as host directed therapy for pulmonary tuberculosis.Research square · 2024Article
- Glycogen synthase kinase 3 inhibition controlsiScience · 2024Article
- Discovery of a blood-based miRNA signature that can predict onset of active tuberculosis among household contacts of TB patients.Frontiers in tuberculosis · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberculosis (TB) accounts for 1.6 million deaths annually and over 25% of deaths due to antimicrobial resistance. Mycobacterium tuberculosis (M.tb) drives MCL-1 expression (family member of anti-apoptotic BCL-2 proteins) to limit apoptosis and grow intracellularly in human macrophages. The feasibility of re-purposing specific MCL-1 and BCL-2 inhibitors to limit M.tb growth, using inhibitors that are in clinical trials and FDA-approved for cancer treatment has not be tested previously. We show that specifically inhibiting MCL-1 and BCL-2 induces apoptosis of M.tb-infected macrophages, and markedly reduces M.tb growth in human and murine macrophages, and in a pre-clinical model of human granulomas. MCL-1 and BCL-2 inhibitors limit growth of drug resistant and susceptible M.tb in macrophages and act in additive fashion with the antibiotics isoniazid and rifampicin. This exciting work uncovers targeting the intrinsic apoptosis pathway as a promising approach for TB host-directed therapy. Since safety and activity studies are underway in cancer clinics for MCL-1 and BCL-2 inhibitors, we expect that re-purposing them for TB treatment should translate more readily and rapidly to the clinic. Thus, the work supports further development of this host-directed therapy approach to augment current TB treatment.
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Registered trials
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.