Shigella hijacks the exocyst to cluster macropinosomes for efficient vacuolar escape.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
06
04
2020
accepted:
20
07
2020
revised:
11
09
2020
pubmed:
1
9
2020
medline:
6
10
2020
entrez:
1
9
2020
Statut:
epublish
Résumé
Shigella flexneri invades host cells by entering within a bacteria-containing vacuole (BCV). In order to establish its niche in the host cytosol, the bacterium ruptures its BCV. Contacts between S. flexneri BCV and infection-associated macropinosomes (IAMs) formed in situ have been reported to enhance BCV disintegration. The mechanism underlying S. flexneri vacuolar escape remains however obscure. To decipher the molecular mechanism priming the communication between the IAMs and S. flexneri BCV, we performed mass spectrometry-based analysis of the magnetically purified IAMs from S. flexneri-infected cells. While proteins involved in host recycling and exocytic pathways were significantly enriched at the IAMs, we demonstrate more precisely that the S. flexneri type III effector protein IpgD mediates the recruitment of the exocyst to the IAMs through the Rab8/Rab11 pathway. This recruitment results in IAM clustering around S. flexneri BCV. More importantly, we reveal that IAM clustering subsequently facilitates an IAM-mediated unwrapping of the ruptured vacuole membranes from S. flexneri, enabling the naked bacterium to be ready for intercellular spread via actin-based motility. Taken together, our work untangles the molecular cascade of S. flexneri-driven host trafficking subversion at IAMs to develop its cytosolic lifestyle, a crucial step en route for infection progression at cellular and tissue level.
Identifiants
pubmed: 32866204
doi: 10.1371/journal.ppat.1008822
pii: PPATHOGENS-D-20-00683
pmc: PMC7485983
doi:
Substances chimiques
Bacterial Proteins
0
Virulence Factors
0
rab11 protein
EC 3.6.1.-
RAB8A protein, human
EC 3.6.1.-.
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008822Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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