Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence.
A549 Cells
Animals
Autophagy
/ immunology
Bacterial Outer Membrane Proteins
/ genetics
Cell Line
Chlorocebus aethiops
Cytosol
/ microbiology
Disease Models, Animal
Endothelial Cells
/ microbiology
Female
Gene Knockout Techniques
Humans
Immune Evasion
Macrophages
/ immunology
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins
Polyubiquitin
/ metabolism
Rickettsia
/ genetics
Rickettsia Infections
/ immunology
Transcriptome
Vero Cells
Virulence
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
06
09
2018
accepted:
10
09
2019
pubmed:
16
10
2019
medline:
1
7
2020
entrez:
16
10
2019
Statut:
ppublish
Résumé
Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri. Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy.
Identifiants
pubmed: 31611642
doi: 10.1038/s41564-019-0583-6
pii: 10.1038/s41564-019-0583-6
pmc: PMC6988571
mid: NIHMS1539630
doi:
Substances chimiques
Bacterial Outer Membrane Proteins
0
Map1lc3b protein, mouse
0
Microtubule-Associated Proteins
0
Polyubiquitin
120904-94-1
OMPA outer membrane proteins
149024-69-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2538-2551Subventions
Organisme : NIAID NIH HHS
ID : R01 AI120694
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI138550
Pays : United States
Organisme : NIGMS NIH HHS
ID : T34 GM008718
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI109044
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)
ID : S10 OD020062-01
Pays : International
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NIH HHS
ID : S10 OD020062
Pays : United States
Organisme : NIGMS NIH HHS
ID : F32 GM120956
Pays : United States
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