ArticleProceedings of the National Academy of Sciences of the United States of America2013
Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
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- Unravelling the protective effects: PknJ modulates MmaA4 expression and rifampicin susceptibility in Mycobacterium bovis BCG.Archives of microbiology · 2026Article
- The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas.Nature immunology · 2026Article
- sRNA centered signaling activates nitrate respiration and enhances Cronobacter sakazakii virulence in host environments.Nature communications · 2026Article
- Novel genes arise from genomic deletions across the bacterial tree of life.bioRxiv : the preprint server for biology · 2026Article
- ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria.Cell reports · 2025Article
- Pathogenicity and virulence ofVirulence · 2025Review
- Effective killing ofMicrobiology spectrum · 2025Article
- 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.Advanced healthcare materials · 2025Article
- Study on the impact of common air pollution indicators on tuberculosis incidence in high-TB-burden countries worldwide.Frontiers in public health · 2025Article
- Efficacy and Possible Mechanism(s) of Action of Gallium Tetraphenylporphyrin Nanoparticles against HIV-TB Coinfection in anACS infectious diseases · 2024Article
- Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.Redox biology · 2024Review
- Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8Nature microbiology · 2024Article
- Orphan response regulator NnaR is critical for nitrate and nitrite assimilation inFrontiers in cellular and infection microbiology · 2024Article
- Mycothiol maintains the homeostasis and signalling of nitric oxide in Streptomyces coelicolor A3(2) M145.BMC microbiology · 2023Article
- Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- The Effects of Paroxetine on Benthic Microbial Food Web and Nitrogen Transformation in River Sediments.International journal of environmental research and public health · 2022Article
- Moxifloxacin-Mediated Killing of Mycobacterium tuberculosis Involves Respiratory Downshift, Reductive Stress, and Accumulation of Reactive Oxygen Species.Antimicrobial agents and chemotherapy · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
In high enough concentrations, such as produced by inducible nitric oxide synthase (iNOS), reactive nitrogen species (RNS) can kill Mycobacterium tuberculosis (Mtb). Lesional macrophages in macaques and humans with tuberculosis express iNOS, and mice need iNOS to avoid succumbing rapidly to tuberculosis. However, Mtb's own ability to produce RNS is rarely considered, perhaps because nitrate reduction to nitrite is only prominent in axenic Mtb cultures at oxygen tensions ≤1%. Here we found that cultures of Mtb-infected human macrophages cultured at physiologic oxygen tensions produced copious nitrite. Surprisingly, the nitrite arose from the Mtb, not the macrophages. Mtb responded to nitrite by ceasing growth; elevating levels of ATP through reduced consumption; and altering the expression of 120 genes associated with adaptation to acid, hypoxia, nitric oxide, oxidative stress, and iron deprivation. The transcriptomic effect of endogenous nitrite was distinct from that of nitric oxide. Thus, whether or not Mtb is hypoxic, the host expresses iNOS, or hypoxia impairs the action of iNOS, Mtb in vivo is likely to encounter RNS by producing nitrite. Endogenous nitrite may slow Mtb's growth and prepare it to resist host stresses while the pathogen waits for immunopathology to promote its transmission.
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Registered trials
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