PUBLICATION
The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness
- Authors
- Lagune, M., Le Moigne, V., Johansen, M.D., Vásquez Sotomayor, F., Daher, W., Petit, C., Cosentino, G., Paulowski, L., Gutsmann, T., Wilmanns, M., Maurer, F.P., Herrmann, J.L., Girard-Misguich, F., Kremer, L.
- ID
- ZDB-PUB-220813-9
- Date
- 2022
- Source
- PLoS pathogens 18: e1010771 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Mice
- Mycobacterium*/genetics
- Mycobacterium abscessus*/genetics
- Mycobacterium marinum*/metabolism
- Mycobacterium tuberculosis*/genetics
- Type VII Secretion Systems*/genetics
- Type VII Secretion Systems*/metabolism
- Zebrafish/metabolism
- PubMed
- 35960766 Full text @ PLoS Pathog.
Citation
Lagune, M., Le Moigne, V., Johansen, M.D., Vásquez Sotomayor, F., Daher, W., Petit, C., Cosentino, G., Paulowski, L., Gutsmann, T., Wilmanns, M., Maurer, F.P., Herrmann, J.L., Girard-Misguich, F., Kremer, L. (2022) The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness. PLoS pathogens. 18:e1010771.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping