ArticleAmerican journal of respiratory cell and molecular biology2015
DosS Is required for the complete virulence of mycobacterium tuberculosis in mice with classical granulomatous lesions.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway with Mycobacterium tuberculosis adaptation to nitric oxide and iron limitation stress.PLoS genetics · 2026Article
- The terminal heme synthetic enzyme, coproheme decarboxylase, negatively regulates heme uptake in Mycobacterium tuberculosis.The Journal of biological chemistry · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway withbioRxiv : the preprint server for biology · 2026Article
- Serine/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress.PLoS genetics · 2026Article
- Mycobacterial MutT1-mediated dephosphorylation of the sensor histidine kinases reveals a new link in the regulation of the two-component signaling.Nucleic acids research · 2025Article
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
- Backtranslation of human RNA biosignatures of tuberculosis disease risk into the preclinical pipeline is condition dependent.mSphere · 2025Article
- Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator.PLoS genetics · 2024Article
- Article
- Exogenously Scavenged and Endogenously Synthesized Heme Are Differentially Utilized by Mycobacterium tuberculosis.Microbiology spectrum · 2022Article
- PrrA modulates Mycobacterium tuberculosis response to multiple environmental cues and is critically regulated by serine/threonine protein kinases.PLoS genetics · 2022Article
- Response to Hypoxia and the Ensuing Dysregulation of Inflammation ImpactsAmerican journal of respiratory and critical care medicine · 2022Article
- Mycobacterium tuberculosis DosS binds HRedox biology · 2022Article
- Therapeutic efficacy of antimalarial drugs targeting DosRS signaling inScience translational medicine · 2022Article
- Targeted dose delivery of Mycobacterium tuberculosis in mice using silicon antifoaming agent via aerosol exposure system.PloS one · 2022Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- Targeting Mycobacterium tuberculosis response to environmental cues for the development of effective antitubercular drugs.PLoS biology · 2021Article
- Antiretroviral therapy does not reduce tuberculosis reactivation in a tuberculosis-HIV coinfection model.The Journal of clinical investigation · 2020Article
- Chronic Immune Activation in TB/HIV Co-infection.Trends in microbiology · 2020Review
- Inhibiting DosRST as a new approach to tuberculosis therapy.Future medicinal chemistry · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) must counter hypoxia within granulomas to persist. DosR, in concert with sensor kinases DosS and DosT, regulates the response to hypoxia. Yet Mtb lacking functional DosR colonize the lungs of C57Bl/6 mice, presumably owing to the lack of organized lesions with sufficient hypoxia in that model. We compared the phenotype of the Δ-dosR, Δ-dosS, and Δ-dosT mutants to Mtb using C3HeB/FeJ mice, an alternate mouse model where lesions develop hypoxia. C3HeB/FeJ mice were infected via aerosol. The progression of infection was analyzed by tissue bacterial burden and histopathology. A measure of the comparative global immune responses was also analyzed. Although Δ-dosR and Δ-dosT grew comparably to wild-type Mtb, Δ-dosS exhibited a significant defect in bacterial burden and pathology in vivo, accompanied by ablated proinflammatory response. Δ-dosS retained the ability to induce DosR. The Δ-dosS mutant was also attenuated in murine macrophages ex vivo, with evidence of reduced expression of the proinflammatory signature. Our results show that DosS, but not DosR and DosT, is required by Mtb to survive in C3HeB/FeJ mice. The attenuation of Δ-dosS is not due to its inability to induce the DosR regulon, nor is it a result of the accumulation of hypoxia. That the in vivo growth restriction of Δ-dosS could be mimicked ex vivo suggested sensitivity to macrophage oxidative burst. Anoxic caseous centers within tuberculosis lesions eventually progress to cavities. Our results provide greater insight into the molecular mechanisms of Mtb persistence within host lungs.
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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.