ArticleProceedings of the National Academy of Sciences of the United States of America2016
Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 202 citations in OpenAlex.
- The mycomembrane proteins PorH and ProtX are inserted at polar growth zones and linked to the cell wall.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Type VII secretion system promotes Streptococcus agalactiae virulence through magnesium acquisition and capsule maintenance.Veterinary research · 2026Article
- Tyloxapol inhibits ESX-1 secretion inJournal of bacteriology · 2026Article
- Sec and Tat Mediated Secretion Safeguards Mycobacterium tuberculosis Membrane Homeostasis.Molecular & cellular proteomics : MCP · 2026Article
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- Gene conversion is a key driver of diversity hotspots inbioRxiv : the preprint server for biology · 2026Article
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- Functional analysis of type VII secretion system links to host immune evasion mechanism inFrontiers in cellular and infection microbiology · 2026Review
- Secreted proteins ofFrontiers in tuberculosis · 2026Review
- Protein Architecture and Composition in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Sigma factor M induces an ESX-4-focused regulon inFrontiers in tuberculosis · 2026Article
- Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance.Nature communications · 2025Article
- Control of Mycobacterium tuberculosis protein secretion by ESX-4 and the outer membrane EsxUT-EsxEF complex.Nature communications · 2025Article
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- ESX-5 Deletions inbioRxiv : the preprint server for biology · 2025Article
- Loss of the ESX-5 secretion locus inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Vitamin C potentiates the killing ofmBio · 2025Article
- An unusual genetic switch controlsbioRxiv : the preprint server for biology · 2025Article
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79 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) encodes five type VII secretion systems (T7SS), designated ESX-1-ESX-5, that are critical for growth and pathogenesis. The best characterized is ESX-1, which profoundly impacts host cell interactions. In contrast, the ESX-3 T7SS is implicated in metal homeostasis, but efforts to define its function have been limited by an inability to recover deletion mutants. We overcame this impediment using medium supplemented with various iron complexes to recover mutants with deletions encompassing select genes within esx-3 or the entire operon. The esx-3 mutants were defective in uptake of siderophore-bound iron and dramatically accumulated cell-associated mycobactin siderophores. Proteomic analyses of culture filtrate revealed that secretion of EsxG and EsxH was codependent and that EsxG-EsxH also facilitated secretion of several members of the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) protein families (named for conserved PE and PPE N-terminal motifs). Substrates that depended on EsxG-EsxH for secretion included PE5, encoded within the esx-3 locus, and the evolutionarily related PE15-PPE20 encoded outside the esx-3 locus. In vivo characterization of the mutants unexpectedly showed that the ESX-3 secretion system plays both iron-dependent and -independent roles in Mtb pathogenesis. PE5-PPE4 was found to be critical for the siderophore-mediated iron-acquisition functions of ESX-3. The importance of this iron-acquisition function was dependent upon host genotype, suggesting a role for ESX-3 secretion in counteracting host defense mechanisms that restrict iron availability. Further, we demonstrate that the ESX-3 T7SS secretes certain effectors that are important for iron uptake while additional secreted effectors modulate virulence in an iron-independent fashion.
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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.