ArticleNature structural & molecular biology2015
The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.
Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 144 citations in OpenAlex.
- Association between human genomes and mycobacterial genomes contributes to severity and transmissibility of pulmonary tuberculosis.iScience · 2026Article
- A Type VII-secreted toxin enables inter-mycobacterial competition.Nature communications · 2026Article
- Characterizing the tuberculosis and type 2 diabetes mellitus comorbidity in a South African cohort using untargeted GCxGC-TOFMS metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Secreted proteins ofFrontiers in tuberculosis · 2026Review
- Protein-Mediated Virulence in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Control of Mycobacterium tuberculosis protein secretion by ESX-4 and the outer membrane EsxUT-EsxEF complex.Nature communications · 2025Article
- An unusual genetic switch controlsbioRxiv : the preprint server for biology · 2025Article
- Comprehensive genomic analysis of type VI secretion system diversity and associated proteins inMicrobial genomics · 2025Article
- Targeted Regulation of HSP70 by the ARP2/3 Complex in Mammary Epithelial Cells and Its Impact on Host Cell Apoptosis.Biomolecules · 2025Article
- Identifying a type of toxic effectors exported by the type VII secretion system to enhance competitive fitness inFrontiers in cellular and infection microbiology · 2025Article
- Iron-restricted Mycobacterium tuberculosis exports pathogenicity factors packed in extracellular vesicles.PloS one · 2025Article
- Article
- ADP-ribosyltransferase-based biocatalysis of nonhydrolyzable NAD+ analogs.The Journal of biological chemistry · 2025Article
- TowardMicroorganisms · 2024Review
- Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection.Nature communications · 2024Article
- Comprehensive pan-genome analysis of Mycobacterium marinum: insights into genomic diversity, evolution, and pathogenicity.Scientific reports · 2024Article
- Genome-wide screen of Mycobacterium tuberculosis-infected macrophages revealed GID/CTLH complex-mediated modulation of bacterial growth.Nature communications · 2024Article
- Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet.Nature communications · 2024Article
- Article
- Evolution of fungal tuberculosis necrotizing toxin (TNT) domain-containing enzymes reveals divergent adaptations to enhance NAD cleavage.Protein science : a publication of the Protein Society · 2024Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms.
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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.