Cited by 35Tuberculosis Research and EpidemiologyBacterial Genetics and BiotechnologyMycobacterium research and diagnosis

EspL is essential for virulence and stabilizes EspE, EspF and EspH levels in Mycobacterium tuberculosis

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Sala, Claudia, Odermatt, Nina T., Soler-Arnedo, Paloma, Gülen, Muhammet F., von Schultz, Sofia, Benjak, Andrej, Cole, Stewart T.·2018·PLOS Pathogens

Abstract

The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis, one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 115 amino acids, is essential for mediating ESX-1-dependent virulence and for stabilization of EspE, EspF and EspH protein levels. Indeed, an espL knock-out mutant was unable to replicate intracellularly, secrete ESX-1 substrates or stimulate innate cytokine production. Moreover, proteomic studies detected greatly reduced amounts of EspE, EspF and EspH in the espL mutant as compared to the wild type strain, suggesting a role for EspL as a chaperone. The latter conclusion was further supported by discovering that EspL interacts with EspD, which was previously demonstrated to stabilize the ESX-1 substrates and effector proteins, EspA and EspC. Loss of EspL also leads to downregulation in M. tuberculosis of WhiB6, a redox-sensitive transcriptional activator of ESX-1 genes. Overall, our data highlight the importance of a so-far overlooked, though conserved, component of the ESX-1 secretion system and begin to delineate the role played by EspE, EspF and EspH in virulence and host-pathogen interaction.

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Authors
Sala, C., Odermatt, N. T., Soler-Arnedo, P., Gülen, M. F., von Schultz, S., Benjak, A., & Cole, S. T.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
  • Sala, Claudia
  • Cole, Stewart T.
Venue
PLOS Pathogens
Published
2018-12-20
Volume
14
Issue
12
Pages
e1007491
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W2904946914
Cited by
35
References
69
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 8
FWCI
3.78
Type
journal article
Language
en
Open access
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_162641)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Keywords
ESX-1 secretion system, Mycobacterium tuberculosis, virulence, ESPE, EspF, EspD, molecular chaperones, protein stabilization, intracellular replication, host-pathogen interaction, type VII secretion system
MeSH terms
THP-1 Cells, Antigens, Bacterial, Bacterial Proteins, Humans, Mycobacterium tuberculosis, Tuberculosis, Virulence, Virulence Factors

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