ArticlePLoS pathogens2018
EspH is a hypervirulence factor for Mycobacterium marinum and essential for the secretion of the ESX-1 substrates EspE and EspF.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 48 citations in OpenAlex.
- Comparative genomics and transcriptomics of rough and smooth Mycobacterium marinum focusing on ESX-1, ESX-6 and LOS genes.Scientific reports · 2026Article
- Review
- Sec and Tat Mediated Secretion Safeguards Mycobacterium tuberculosis Membrane Homeostasis.Molecular & cellular proteomics : MCP · 2026Article
- Genome-wide phenotypic insights into mycobacterial virulence using Drosophila melanogaster.PLoS pathogens · 2025Article
- Review
- Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment.FEMS microbiology reviews · 2024Review
- Proteomics from compartment-specific APEX2 labeling in Mycobacterium tuberculosis reveals Type VII secretion substrates in the cell wall.Cell chemical biology · 2024Article
- Article
- The ESX-1 Substrate PPE68 Has a Key Function in ESX-1-Mediated Secretion in Mycobacterium marinum.mBio · 2022Article
- Methanotrophy by a Mycobacterium species that dominates a cave microbial ecosystem.Nature microbiology · 2022Article
- Article
- The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Stapling of Peptides Potentiates the Antibiotic Treatment ofAntibiotics (Basel, Switzerland) · 2022Article
- Article
- Type VII secretion systems: structure, functions and transport models.Nature reviews. Microbiology · 2021Review
- Priming mycobacterial ESX-secreted protein B to form a channel-like structure.Current research in structural biology · 2021Article
- The genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens.PLoS pathogens · 2021Review
- Modeling Tubercular ESX-1 Secretion Using Mycobacterium marinum.Microbiology and molecular biology reviews : MMBR · 2020Review
- Conserved ESX-1 Substrates EspE and EspF Are Virulence Factors That Regulate Gene Expression.Infection and immunity · 2020Article
- Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccCMolecular microbiology · 2020Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogen Mycobacterium tuberculosis employs a range of ESX-1 substrates to manipulate the host and build a successful infection. Although the importance of ESX-1 secretion in virulence is well established, the characterization of its individual components and the role of individual substrates is far from complete. Here, we describe the functional characterization of the Mycobacterium marinum accessory ESX-1 proteins EccA1, EspG1 and EspH, i.e. proteins that are neither substrates nor structural components. Proteomic analysis revealed that EspG1 is crucial for ESX-1 secretion, since all detectable ESX-1 substrates were absent from the cell surface and culture supernatant in an espG1 mutant. Deletion of eccA1 resulted in minor secretion defects, but interestingly, the severity of these secretion defects was dependent on the culture conditions. Finally, espH deletion showed a partial secretion defect; whereas several ESX-1 substrates were secreted in normal amounts, secretion of EsxA and EsxB was diminished and secretion of EspE and EspF was fully blocked. Interaction studies showed that EspH binds EspE and therefore could function as a specific chaperone for this substrate. Despite the observed differences in secretion, hemolytic activity was lost in all M. marinum mutants, implying that hemolytic activity is not strictly correlated with EsxA secretion. Surprisingly, while EspH is essential for successful infection of phagocytic host cells, deletion of espH resulted in a significantly increased virulence phenotype in zebrafish larvae, linked to poor granuloma formation and extracellular outgrowth. Together, these data show that different sets of ESX-1 substrates play different roles at various steps of the infection cycle of M. marinum.
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