ArticleInfection and immunity2016
Role of Metal-Dependent Regulation of ESX-3 Secretion in Intracellular Survival of Mycobacterium tuberculosis.
Article in Infection and immunity, 2016. 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, 40 citations in OpenAlex.
- Article
- Control of Mycobacterium tuberculosis protein secretion by ESX-4 and the outer membrane EsxUT-EsxEF complex.Nature communications · 2025Article
- Mycobacterium susceptibility to ivermectin by inhibition of eccD3, an ESX-3 secretion system component.PLoS computational biology · 2025Article
- The role of transcriptional regulators in metal ion homeostasis ofFrontiers in cellular and infection microbiology · 2024Review
- The cell envelope of Mycobacterium abscessus and its role in pathogenesis.PLoS pathogens · 2023Review
- In silico EsxG EsxH rational epitope selection: Candidate epitopes for vaccine design against pulmonary tuberculosis.PloS one · 2023Article
- Types and functions of heterogeneity in mycobacteria.Nature reviews. Microbiology · 2022Review
- Kupyaphores are zinc homeostatic metallophores required for colonization ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Proteome Profiling ofACS omega · 2022Article
- Insights into the ancestry evolution of theNAR genomics and bioinformatics · 2021Article
- Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM.The Journal of membrane biology · 2021Review
- Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease.Respiratory research · 2021Review
- ComprehensiveMicrobial genomics · 2021Article
- A novel stress-inducible CmtR-ESX3-ZnThe Journal of biological chemistry · 2020Article
- Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system.The Journal of biological chemistry · 2020Article
- Article
- The sensor kinase MtrB ofThe Journal of biological chemistry · 2019Article
- Article
- Protein Export into and across the Atypical Diderm Cell Envelope of Mycobacteria.Microbiology spectrum · 2019Review
- Immunology ofMicrobiology spectrum · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
More people die every year from Mycobacterium tuberculosis infection than from infection by any other bacterial pathogen. Type VII secretion systems (T7SS) are used by both environmental and pathogenic mycobacteria to secrete proteins across their complex cell envelope. In the nonpathogen Mycobacterium smegmatis, the ESX-1 T7SS plays a role in conjugation, and the ESX-3 T7SS is involved in metal homeostasis. In M. tuberculosis, these secretion systems have taken on roles in virulence, and they also are targets of the host immune response. ESX-3 secretes a heterodimer composed of EsxG (TB9.8) and EsxH (TB10.4), which impairs phagosome maturation in macrophages and is essential for virulence in mice. Given the importance of EsxG and EsxH during infection, we examined their regulation. With M. tuberculosis, the secretion of EsxG and EsxH was regulated in response to iron and zinc, in accordance with the previously described transcriptional response of the esx-3 locus to these metals. While iron regulated the esx-3 expression in both M. tuberculosis and M. smegmatis, there is a significant difference in the dynamics of this regulation. In M. smegmatis, the esx-3 locus behaved like other iron-regulated genes such as mbtB In M. tuberculosis, both iron and zinc modestly repressed esx-3 expression. Diminished secretion of EsxG and EsxH in response to these metals altered the interaction of M. tuberculosis with macrophages, leading to impaired intracellular M. tuberculosis survival. Our findings detail the regulatory differences of esx-3 in M. tuberculosis and M. smegmatis and demonstrate the importance of metal-dependent regulation of ESX-3 for virulence in M. tuberculosis.
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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.