ArticleJournal of bacteriology2013
Phenotypic profiling of Mycobacterium tuberculosis EspA point mutants reveals that blockage of ESAT-6 and CFP-10 secretion in vitro does not always correlate with attenuation of virulence.
Article in Journal of bacteriology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.Tuberculosis (Edinburgh, Scotland) · 2025Article
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- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection inbioRxiv : the preprint server for biology · 2025Article
- Comparative transcriptomic signatures of virulent and attenuatedFrontiers in cellular and infection microbiology · 2025Article
- Uptake-independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates.The EMBO journal · 2023Article
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- Proteo-genetic analysis reveals clear hierarchy of ESX-1 secretion inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mycobacterium tuberculosis EspK Has Active but Distinct Roles in the Secretion of EsxA and EspB.Journal of bacteriology · 2022Article
- 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
- Article
- Article
- A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium-Host Interaction.Cells · 2021Review
- Pathogenic Determinants of theMicroorganisms · 2021Article
- The genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens.PLoS pathogens · 2021Review
- Conserved ESX-1 Substrates EspE and EspF Are Virulence Factors That Regulate Gene Expression.Infection and immunity · 2020Article
- Rv1717 Is a Cell Wall - Associated β-Galactosidase ofFrontiers in microbiology · 2020Article
- High-Throughput Screen for Cell Wall Synthesis Network Module inFrontiers in bioengineering and biotechnology · 2020Article
- A New ESX-1 Substrate in Mycobacterium marinum That Is Required for Hemolysis but Not Host Cell Lysis.Journal of bacteriology · 2019Article
- Protein Export into and across the Atypical Diderm Cell Envelope of Mycobacteria.Microbiology spectrum · 2019Review
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
The EspA protein of Mycobacterium tuberculosis is essential for the type VII ESX-1 protein secretion apparatus, which delivers the principal virulence factors ESAT-6 and CFP-10. In this study, site-directed mutagenesis of EspA was performed to elucidate its influence on the ESX-1 system. Replacing Trp(55) (W55) or Gly(57) (G57) residues in the putative W-X-G motif of EspA with arginines impaired ESAT-6 and CFP-10 secretion in vitro and attenuated M. tuberculosis. Replacing the Phe(50) (F50) and Lys(62) (K62) residues, which flank the W-X-G motif, with arginine and alanine, respectively, destabilized EspA, abolished ESAT-6 and CFP-10 secretion in vitro, and attenuated M. tuberculosis. Likewise, replacing the Phe(5) (F5) and Lys(41) (K41) residues with arginine and alanine, respectively, also destabilized EspA and blocked ESAT-6 and CFP-10 secretion in vitro. However, these two particular mutations did not attenuate M. tuberculosis in cellular models of infection or during acute infection in mice. We have thus identified amino acid residues in EspA that are important for facilitating ESAT-6 and CFP-10 secretion and virulence. However, our data also indicate for the first time that blockage of M. tuberculosis ESAT-6 and CFP-10 secretion in vitro and attenuation are mutually exclusive.
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