Global mapping of Salmonella enterica-host protein-protein interactions during infection.
Adaptor Proteins, Signal Transducing
Animals
Bacteria
Bacterial Proteins
/ metabolism
Epithelial Cells
/ microbiology
Female
HeLa Cells
Host-Pathogen Interactions
/ physiology
Humans
Macrophages
/ microbiology
Male
Mice
Protein Interaction Domains and Motifs
RAW 264.7 Cells
Salmonella enterica
/ genetics
Salmonella typhimurium
/ metabolism
FMNL
NPC1
PDZD8
actin bundling
bacterial pathogen
cholesterol trafficking
effectors
protein-protein interactions
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
11 Aug 2021
11 Aug 2021
Historique:
received:
28
04
2020
revised:
24
02
2021
accepted:
21
05
2021
pubmed:
9
7
2021
medline:
15
12
2021
entrez:
8
7
2021
Statut:
ppublish
Résumé
Intracellular bacterial pathogens inject effector proteins to hijack host cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32 Salmonella enterica serovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effectors and quantified PPIs in macrophages and epithelial cells. We identified 446 effector-host PPIs, 25 of which were previously described, and validated 13 by reciprocal co-immunoprecipitation. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. We demonstrate that SseJ, SseL, and SifA modulate cholesterol accumulation at the Salmonella-containing vacuole (SCV) partially via the cholesterol transporter Niemann-Pick C1 protein. PipB recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by phosphorylating formin-like proteins. This study provides a method for probing host-pathogen PPIs during infection and a resource for interrogating STm effector mechanisms.
Identifiants
pubmed: 34237247
pii: S1931-3128(21)00282-1
doi: 10.1016/j.chom.2021.06.004
pmc: PMC8561747
mid: NIHMS1723390
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Bacterial Proteins
0
PDZD8 protein, human
0
PipB protein, Salmonella enterica
0
SifA protein, Salmonella
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1316-1332.e12Subventions
Organisme : Intramural NIH HHS
ID : ZIA AI000909
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
PLoS One. 2014 Jul 09;9(7):e99820
pubmed: 25007190
Cell. 2009 Dec 24;139(7):1255-67
pubmed: 20064372
Mol Biol Cell. 2005 Sep;16(9):4108-23
pubmed: 15987736
Nature. 1981 May 21;291(5812):238-9
pubmed: 7015147
PLoS One. 2016 Sep 14;11(9):e0161965
pubmed: 27627128
Nat Protoc. 2015 Oct;10(10):1567-93
pubmed: 26379230
Cell Syst. 2018 Sep 26;7(3):323-338.e6
pubmed: 30077634
Trends Microbiol. 2012 Aug;20(8):360-8
pubmed: 22652164
Curr Biol. 2012 Jun 5;22(11):1005-12
pubmed: 22608513
J Proteome Res. 2011 Mar 4;10(3):954-67
pubmed: 21138299
Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13497-502
pubmed: 16938850
J Bacteriol. 2011 Oct;193(20):5607-15
pubmed: 21856851
Proteomics. 2009 Dec;9(23):5296-302
pubmed: 19834901
Front Cell Infect Microbiol. 2018 Jan 05;7:528
pubmed: 29354599
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15264-9
pubmed: 11742086
J Biol Chem. 2009 Nov 27;284(48):33151-60
pubmed: 19801640
Bioinformatics. 2008 Jun 15;24(12):1461-2
pubmed: 18441000
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7606-11
pubmed: 17446270
Nat Commun. 2018 Oct 23;9(1):4408
pubmed: 30352994
Bioinformatics. 2009 Apr 15;25(8):1091-3
pubmed: 19237447
Nature. 1970 Aug 15;227(5259):680-5
pubmed: 5432063
Nature. 2011 Dec 21;481(7381):365-70
pubmed: 22190034
Nat Commun. 2017 Mar 22;8:14832
pubmed: 28327544
Bioinformatics. 2002;18 Suppl 1:S96-104
pubmed: 12169536
Methods Mol Biol. 2008;431:201-11
pubmed: 18287758
Mol Cell Proteomics. 2013 Jun;12(6):1632-43
pubmed: 23459991
Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):E123-31
pubmed: 23251033
J Bacteriol. 2013 Mar;195(6):1120-32
pubmed: 23264574
Methods Mol Biol. 2019;1949:137-152
pubmed: 30790254
Cell Mol Immunol. 2020 Jan;17(1):50-63
pubmed: 31804619
Nat Rev Microbiol. 2015 Apr;13(4):191-205
pubmed: 25749450
Bioinformatics. 2012 Jan 15;28(2):288-9
pubmed: 22113085
EMBO J. 2003 Jan 2;22(1):78-88
pubmed: 12505986
Microbes Infect. 2012 Feb;14(2):148-54
pubmed: 21988961
Traffic. 2002 Jun;3(6):407-15
pubmed: 12010459
Mol Microbiol. 2008 Apr;68(1):173-85
pubmed: 18333886
Nat Microbiol. 2019 Dec;4(12):2511-2522
pubmed: 31611645
Front Cell Infect Microbiol. 2013 Nov 26;3:76
pubmed: 24324933
Small GTPases. 2014;5:e29513
pubmed: 24914801
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Mol Cell Biol. 2000 Sep;20(18):6872-81
pubmed: 10958683
J Biol Chem. 1988 Dec 15;263(35):18920-8
pubmed: 3198605
Front Cell Infect Microbiol. 2017 Nov 15;7:467
pubmed: 29188194
RNA Biol. 2011 Sep-Oct;8(5):913-21
pubmed: 21788735
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Traffic. 2008 Dec;9(12):2117-29
pubmed: 18785994
Methods. 2011 Jan;53(1):13-9
pubmed: 20708689
Mol Cell. 2018 Aug 16;71(4):637-648.e5
pubmed: 30118682
Methods Cell Biol. 2012;108:367-93
pubmed: 22325611
Nature. 2011 Dec 21;481(7381):371-5
pubmed: 22190037
Plant Cell. 2016 Oct;28(10):2435-2452
pubmed: 27729395
Nat Microbiol. 2020 Sep;5(9):1119-1133
pubmed: 32514074
Sci Rep. 2015 Aug 13;5:12979
pubmed: 26268777
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17733-8
pubmed: 20876119
Infect Immun. 2011 Nov;79(11):4392-400
pubmed: 21875964
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
pubmed: 10829079
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Cell Microbiol. 2004 Nov;6(11):1041-55
pubmed: 15469433
Nat Commun. 2015 May 12;6:7088
pubmed: 25963737
Methods Mol Biol. 2017;1519:285-296
pubmed: 27815887
Gene. 1989 Apr 15;77(1):61-8
pubmed: 2744488
EMBO J. 2017 Nov 2;36(21):3156-3174
pubmed: 28978670
Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22619-22623
pubmed: 31636202
BMC Biol. 2011 Aug 11;9:54
pubmed: 21834987
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Cell Microbiol. 2008 Jan;10(1):20-30
pubmed: 17645553
ChemMedChem. 2016 May 6;11(9):963-71
pubmed: 26990667
Cell Microbiol. 2009 Nov;11(11):1652-70
pubmed: 19614667
Mol Microbiol. 2003 Aug;49(3):685-704
pubmed: 12864852
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Mol Microbiol. 2002 Mar;43(5):1089-103
pubmed: 11918798
J Biol Chem. 2019 Feb 1;294(5):1706-1709
pubmed: 30710017
Cell Rep. 2019 May 14;27(7):2147-2156.e5
pubmed: 31091452
Sci Rep. 2014 Dec 18;4:7531
pubmed: 25519916
Curr Protoc Bioinformatics. 2015 Mar 09;49:8.19.1-8.19.16
pubmed: 25754993
PLoS Pathog. 2019 Jul 24;15(7):e1007959
pubmed: 31339948
Cell Host Microbe. 2012 Nov 15;12(5):657-68
pubmed: 23159055
mSystems. 2016 Jul 12;1(4):
pubmed: 27822540
Sci Rep. 2017 Aug 29;7(1):9791
pubmed: 28852060
FEBS Lett. 2013 Jun 19;587(12):1823-8
pubmed: 23684642
J Biol Chem. 2012 Jan 27;287(5):3087-98
pubmed: 22094460
Cell Host Microbe. 2008 Nov 13;4(5):434-46
pubmed: 18996344
PLoS Pathog. 2012;8(6):e1002773
pubmed: 22761574
Microbiol Mol Biol Rev. 2012 Jun;76(2):331-82
pubmed: 22688816
Cell Host Microbe. 2017 Aug 9;22(2):217-231
pubmed: 28799907
Science. 2006 Jan 13;311(5758):239-42
pubmed: 16339411
Anal Chem. 2014 Apr 1;86(7):3594-601
pubmed: 24579773
Cell Host Microbe. 2008 Apr 17;3(4):233-44
pubmed: 18407067
PLoS Pathog. 2009 Sep;5(9):e1000595
pubmed: 19779561
Proteomics. 2012 May;12(10):1639-55
pubmed: 22611043
Cell Host Microbe. 2015 Jan 14;17(1):58-71
pubmed: 25500191
Nat Protoc. 2019 Jan;14(1):68-85
pubmed: 30464214
Infect Immun. 2008 Jun;76(6):2722-35
pubmed: 18411289
Sci Rep. 2017 Jan 30;7:41408
pubmed: 28134274
Anal Chem. 2003 Feb 1;75(3):663-70
pubmed: 12585499
Nature. 2020 Jul;583(7816):459-468
pubmed: 32353859
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14141-6
pubmed: 18787122
J Biol Chem. 2011 Jul 8;286(27):24023-35
pubmed: 21566117
Protein Expr Purif. 2005 May;41(1):207-34
pubmed: 15915565
Nat Commun. 2020 Jul 20;11(1):3645
pubmed: 32686675
Front Cell Infect Microbiol. 2017 Oct 04;7:432
pubmed: 29046870
Brief Bioinform. 2015 Jul;16(4):658-74
pubmed: 25378435