ArticleNature communications2021
Intracellular localisation of Mycobacterium tuberculosis affects efficacy of the antibiotic pyrazinamide.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 87 citations in OpenAlex.
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- Investigation of cyclic peptides as drug delivery systems for the delivery of the anti-tuberculosis drug pyrazinamide.Nanoscale advances · 2026Article
- Fast-growing intracellular Mycobacterium tuberculosis populations evade antibiotic treatment.Nature communications · 2026Article
- The diagnostic and therapeutic value of FDG PET/CT for infectious diseases in FUO/IUO patients.Annals of nuclear medicine · 2026Article
- Dual human lung models reveal compartment-specific activity of anti-tuberculosis drugs and host-directed therapies.Microbiology spectrum · 2026Article
- Association between overexpression of efflux pumps genes Rv0191 and Rv3008 and pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis: a multi-center study.BMC infectious diseases · 2026Article
- Evaluation of clofazimine-bedaquiline combination as a candidate regimen for macrolide-resistantAntimicrobial agents and chemotherapy · 2026Article
- Essential role of MHC II in the antitubercular efficacy of pyrazinamide.Antimicrobial agents and chemotherapy · 2026Article
- Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes.Nature microbiology · 2026Article
- A review on recent advances in lipid-based drug delivery systems for tuberculosis.Iranian journal of basic medical sciences · 2026Review
- Vacuolar-ATPase inhibitors are antimicrobial agents active against intracellular mycobacteria.Antimicrobial agents and chemotherapy · 2025Article
- PPARγ mediated enhanced lipid biogenesis fuelseLife · 2025Article
- A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics.Nature microbiology · 2025Article
- Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- The Parkinson's drug benztropine possesses histamine receptor 1-dependent host-directed antimicrobial activity against Mycobacterium tuberculosis.npj antimicrobials and resistance · 2025Article
- Innovative Strategies for Combating Multidrug-Resistant Tuberculosis: Advances in Drug Delivery Systems and Treatment.Microorganisms · 2025Review
- Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 5 countries.
Funding
Abstract
To be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis. However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among individual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation and specific microenvironments affect PZA accumulation and efficacy. Our results may explain the potent in vivo efficacy of PZA, compared to its modest in vitro activity, and its critical contribution to TB combination chemotherapy.
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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.