In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2022-8-12), p. 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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010771
DOI:
10.1371/journal.ppat.1010771.g001
DOI:
10.1371/journal.ppat.1010771.g002
DOI:
10.1371/journal.ppat.1010771.g003
DOI:
10.1371/journal.ppat.1010771.g004
DOI:
10.1371/journal.ppat.1010771.s001
DOI:
10.1371/journal.ppat.1010771.s002
DOI:
10.1371/journal.ppat.1010771.s003
DOI:
10.1371/journal.ppat.1010771.s004
DOI:
10.1371/journal.ppat.1010771.s005
DOI:
10.1371/journal.ppat.1010771.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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