ArticleNature microbiology2025
Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.
Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed.
- Systematic Design and Evaluation of Nasal Drug Delivery for Central Nervous System Disease from Experimental to Clinical Application.Pharmaceutics · 2026Review
- Emerging insights into CC and CXC chemokines and their receptors in Mycobacterium tuberculosis infection.FEBS open bio · 2026Review
- Lung mucosal and systemic responses at single-cell resolution in an aerosolized Mycobacterium bovis BCG human challenge model.Cell reports. Medicine · 2026Article
- Advances in biocontainment strategies of engineered microbes for use in humans.Current opinion in microbiology · 2026Review
- The Emerging Role of Immunothrombosis in the Control and Pathogenesis of Mycobacterium tuberculosis.The Journal of infectious diseases · 2026Review
- Controlled human infection with Mycobacterium tuberculosis: practical considerations for clinical trials.The Lancet. Microbe · 2026Review
- Protection against reinfection with Mycobacterium tuberculosis extends across heterologous Mtb lineages.Mucosal immunology · 2026Article
- Rapid resistance evolution against phage cocktails.The ISME journal · 2026Article
- Advances in mycobacteriophage research: from lytic mechanisms to one health applications.Frontiers in cellular and infection microbiology · 2026Review
- Immunotherapy for tuberculosis: emerging modalities, cross-disciplinary innovations, and roadmaps for drug-resistant disease.Frontiers in immunology · 2026Review
- Evolution of split-protein technologies in virology: From mechanistic discovery and diagnostics to therapeutic promise.Journal of virus eradication · 2025Review
- Intravenous iRGD-Guided, RBC-Membrane Camouflaged Lactococcus Lactis Remodels Cold NSCLC and Enhances PD-1 Blockade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Experimental dissection of tuberculosis protective immunity: a human perspective.Frontiers in cellular and infection microbiology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
Abstract
Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim. The triple-kill-switch (TKS) strain showed similar growth kinetics and antibiotic susceptibilities to wild-type Mtb under permissive conditions but was rapidly killed in vitro without trimethoprim and doxycycline. It established infection in mice receiving antibiotics but was rapidly cleared upon cessation of treatment, and no relapse was observed in infected severe combined immunodeficiency mice or Rag
Indexed as
Identifiers
What OpenQuestion holds
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.