A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication.
ADP-Ribosylation Factor 6
/ metabolism
Animals
Bacterial Proteins
/ metabolism
Brucella abortus
/ physiology
Brucellosis
/ immunology
Endosomes
/ metabolism
GTPase-Activating Proteins
/ metabolism
HeLa Cells
Host-Pathogen Interactions
/ genetics
Humans
Mice
Models, Biological
Protein Binding
Protein Transport
Type IV Secretion Systems
Vacuoles
/ microbiology
rab GTP-Binding Proteins
/ metabolism
trans-Golgi Network
Brucella
ACAP1
pathogenesis
retrograde membrane transport
type IV secretion
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
revised:
26
07
2021
received:
06
01
2021
accepted:
30
07
2021
pubmed:
24
8
2021
medline:
15
12
2021
entrez:
23
8
2021
Statut:
ppublish
Résumé
Remodeling of host cellular membrane transport pathways is a common pathogenic trait of many intracellular microbes that is essential to their intravacuolar life cycle and proliferation. The bacterium Brucella abortus generates a host endoplasmic reticulum-derived vacuole (rBCV) that supports its intracellular growth, via VirB Type IV secretion system-mediated delivery of effector proteins, whose functions and mode of action are mostly unknown. Here, we show that the effector BspF specifically promotes Brucella replication within rBCVs by interfering with vesicular transport between the trans-Golgi network (TGN) and recycling endocytic compartment. BspF targeted the recycling endosome, inhibited retrograde traffic to the TGN, and interacted with the Arf6 GTPase-activating Protein (GAP) ACAP1 to dysregulate Arf6-/Rab8a-dependent transport within the recycling endosome, which resulted in accretion of TGN-associated vesicles by rBCVs and enhanced bacterial growth. Altogether, these findings provide mechanistic insight into bacterial modulation of membrane transport used to promote their own proliferation within intracellular vacuoles.
Identifiants
pubmed: 34423453
doi: 10.15252/embj.2021107664
pmc: PMC8488576
doi:
Substances chimiques
ACAP1 protein, human
0
ADP-Ribosylation Factor 6
0
Bacterial Proteins
0
GTPase-Activating Proteins
0
Rab8a protein, mouse
0
Type IV Secretion Systems
0
Arf6 protein, mouse
EC 3.6.5.2
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e107664Subventions
Organisme : NIAID NIH HHS
ID : R01 AI129992
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008336
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI000954
Pays : United States
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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