The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness.
Lagune, M
Le Moigne, V
Johansen, MD
Vásquez Sotomayor, F
Daher, W
Petit, C
Cosentino, G
Paulowski, L
Gutsmann, T
Wilmanns, M
Maurer, FP
Herrmann, J-L
Girard-Misguich, F
Kremer, L
- Publisher:
- Public Library of Science (PLoS)
- Publication Type:
- Journal Article
- Citation:
- PLoS Pathogens, 2022, 18, (8), pp. 1-21
- Issue Date:
- 2022-08
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Lagune, M | |
dc.contributor.author | Le Moigne, V | |
dc.contributor.author | Johansen, MD | |
dc.contributor.author | Vásquez Sotomayor, F | |
dc.contributor.author | Daher, W | |
dc.contributor.author | Petit, C | |
dc.contributor.author | Cosentino, G | |
dc.contributor.author | Paulowski, L | |
dc.contributor.author | Gutsmann, T | |
dc.contributor.author | Wilmanns, M | |
dc.contributor.author | Maurer, FP | |
dc.contributor.author | Herrmann, J-L | |
dc.contributor.author | Girard-Misguich, F | |
dc.contributor.author | Kremer, L | |
dc.date.accessioned | 2022-12-14T02:24:02Z | |
dc.date.available | 2022-07-27 | |
dc.date.available | 2022-12-14T02:24:02Z | |
dc.date.issued | 2022-08 | |
dc.identifier.citation | PLoS Pathogens, 2022, 18, (8), pp. 1-21 | |
dc.identifier.issn | 1553-7366 | |
dc.identifier.issn | 1553-7374 | |
dc.identifier.uri | http://hdl.handle.net/10453/164393 | |
dc.description.abstract | ESX type VII secretion systems are complex secretion machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake and conjugation. We previously reported the role of ESX-4 in modulating Mycobacterium abscessus intracellular survival. The loss of EccB4 was associated with limited secretion of two effector proteins belonging to the WXG-100 family, EsxU and EsxT, and encoded by the esx-4 locus. This prompted us to investigate the function of M. abscessus EsxU and EsxT in vitro and in vivo. Herein, we show that EsxU and EsxT are substrates of ESX-4 and form a stable 1:1 heterodimer that permeabilizes artificial membranes. While expression of esxU and esxT was up-regulated in M. abscessus-infected macrophages, their absence in an esxUT deletion mutant prevented phagosomal membrane disruption while maintaining M. abscessus in an unacidified phagosome. Unexpectedly, the esxUT deletion was associated with a hyper-virulent phenotype, characterised by increased bacterial loads and mortality in mouse and zebrafish infection models. Collectively, these results demonstrate that the presence of EsxU and EsxT dampens survival and persistence of M. abscessus during infection. | |
dc.format | Electronic-eCollection | |
dc.language | eng | |
dc.publisher | Public Library of Science (PLoS) | |
dc.relation.ispartof | PLoS Pathogens | |
dc.relation.isbasedon | 10.1371/journal.ppat.1010771 | |
dc.rights | Copyright: © 2022 Lagune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology | |
dc.subject.classification | Virology | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Bacterial Proteins | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mycobacterium | |
dc.subject.mesh | Mycobacterium abscessus | |
dc.subject.mesh | Mycobacterium marinum | |
dc.subject.mesh | Mycobacterium tuberculosis | |
dc.subject.mesh | Type VII Secretion Systems | |
dc.subject.mesh | Zebrafish | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Bacterial Proteins | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mycobacterium | |
dc.subject.mesh | Mycobacterium abscessus | |
dc.subject.mesh | Mycobacterium marinum | |
dc.subject.mesh | Mycobacterium tuberculosis | |
dc.subject.mesh | Type VII Secretion Systems | |
dc.subject.mesh | Zebrafish | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Zebrafish | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mycobacterium | |
dc.subject.mesh | Mycobacterium marinum | |
dc.subject.mesh | Mycobacterium tuberculosis | |
dc.subject.mesh | Bacterial Proteins | |
dc.subject.mesh | Type VII Secretion Systems | |
dc.subject.mesh | Mycobacterium abscessus | |
dc.title | The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness. | |
dc.type | Journal Article | |
utslib.citation.volume | 18 | |
utslib.location.activity | United States | |
utslib.for | 0605 Microbiology | |
utslib.for | 1107 Immunology | |
utslib.for | 1108 Medical Microbiology | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CFI - Centre for Inflammation | |
utslib.copyright.status | open_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2022-12-14T02:23:49Z | |
pubs.issue | 8 | |
pubs.publication-status | Published | |
pubs.volume | 18 | |
utslib.citation.issue | 8 |
Abstract:
ESX type VII secretion systems are complex secretion machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake and conjugation. We previously reported the role of ESX-4 in modulating Mycobacterium abscessus intracellular survival. The loss of EccB4 was associated with limited secretion of two effector proteins belonging to the WXG-100 family, EsxU and EsxT, and encoded by the esx-4 locus. This prompted us to investigate the function of M. abscessus EsxU and EsxT in vitro and in vivo. Herein, we show that EsxU and EsxT are substrates of ESX-4 and form a stable 1:1 heterodimer that permeabilizes artificial membranes. While expression of esxU and esxT was up-regulated in M. abscessus-infected macrophages, their absence in an esxUT deletion mutant prevented phagosomal membrane disruption while maintaining M. abscessus in an unacidified phagosome. Unexpectedly, the esxUT deletion was associated with a hyper-virulent phenotype, characterised by increased bacterial loads and mortality in mouse and zebrafish infection models. Collectively, these results demonstrate that the presence of EsxU and EsxT dampens survival and persistence of M. abscessus during infection.
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