ArticleScientific reports2017
An attenuated Mycobacterium tuberculosis clinical strain with a defect in ESX-1 secretion induces minimal host immune responses and pathology.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- HowVaccines · 2026Review
- ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria.Cell reports · 2025Article
- Control of antigen presentation on MHC-I by a bacterial secretion system.bioRxiv : the preprint server for biology · 2025Article
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- Correlative 3D imaging method for analysing lesion architecture in susceptible mice infected with Mycobacterium tuberculosis.Disease models & mechanisms · 2025Article
- Comprehensive pan-genome analysis of Mycobacterium marinum: insights into genomic diversity, evolution, and pathogenicity.Scientific reports · 2024Article
- ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restrictseLife · 2024Article
- ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6 specific nanobody restricts M. tuberculosis growth in macrophages.bioRxiv : the preprint server for biology · 2024Article
- Polyphosphate kinase-1 regulates bacterial and host metabolic pathways involved in pathogenesis ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phase variation as a major mechanism of adaptation inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The mutation rate of rpoB gene showed an upward trend with the increase of MIRU10, MIRU39 and QUB4156 repetitive number.BMC genomics · 2023Article
- Evaluation of the Immunogenicity of Recombinant Espb, Espc Proteins fromReports of biochemistry & molecular biology · 2023Article
- Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis-infected macrophages.Cell death discovery · 2021Article
- Reversible gene silencing through frameshift indels and frameshift scars provide adaptive plasticity for Mycobacterium tuberculosis.Nature communications · 2021Article
- Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens.Biomolecules · 2021Review
- Pathogenomic analyses ofMicrobial genomics · 2021Article
- In-host population dynamics ofeLife · 2021Article
- Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins.International journal of molecular sciences · 2020Review
- VapBC22 toxin-antitoxin system fromScience advances · 2020Article
- Differential determinants of virulence in twoVirulence · 2019Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system. Genetic complementation with a plasmid carrying the M.tb H37Rv sequence of eccCa1-eccCb1-pe35 re-established EsxA secretion, host specific EsxA T-cell responses, and increased strain virulence. The ESX-1 secretion defect prevents several virulence factors from being functional during infection and therefore attenuates M.tb. It precludes specific T-cell responses against strong antigens and we found very little in vivo cytokine production, gross pathology or granuloma formation in lungs from M.tb DK9897 infected animals. This coincides with M.tb DK9897 being unable to disrupt the phagosome membrane and make contact to the cytosol.
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