title: A novel contribution of spvB to pathogenesis of Salmonella Typhimurium by inhibiting autophagy in host cells.
abstract: Salmonella plasmid virulence genes (spv) are highly conserved in strains of clinically important Salmonella serovars. It is essential for Salmonella plasmid-correlated virulence, although the exact mechanism remains to be elucidated. Autophagy has been reported to play an important role in host immune responses limiting Salmonella infection. Our previous studies demonstrated that Salmonella conjugative plasmid harboring spv genes could enhance bacterial cytotoxicity by inhibiting autophagy. In the present study, we investigated whether spvB, which is one of the most important constituents of spv ORF could intervene in autophagy pathway. Murine macrophage-like cells J774A.1, human epithelial HeLa cells, and BALB/c mice infected with Salmonella Typhimurium wild type, mutant and complementary strains (carrying or free spvB or complemented only with ADP-ribosyltransferase activity of SpvB) were used in vitro and in vivo assay, respectively. To further explore the molecular mechanisms, both SpvB ectopic eukaryotic expression system and cells deficient in essential autophagy components by siRNA were generated. Results indicated that spvB could suppress autophagosome formation through its function in depolymerizing actin, and aggravate inflammatory injury of the host in response to S. Typhimurium infection. Our studies demonstrated virulence of spvB involving in inhibition of autophagic flux for the first time, which could provide novel insights into Salmonella pathogenesis, and have potential application to develop new antibacterial strategies for Salmonellosis.
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D001343:Autophagy; D001426:Bacterial Proteins / Q000378:metabolism*; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012480:Salmonella Infections / Q000382:microbiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D037521:Virulence Factors
keywords: Salmonella; autophagic flux; autophagy; spvB
references.citation: Int J Med Microbiol. 2011 Feb;301(2):117-24
references.pmid: 21036103
references.citation: Front Microbiol. 2011 Jun 14;2:129
references.pmid: 21716657
references.citation: Mol Cell. 2014 Jul 17;55(2):238-52
references.pmid: 24954904
references.citation: Infect Immun. 1996 Nov;64(11):4739-43
references.pmid: 8890234
references.citation: Mol Microbiol. 2007 Dec;66(6):1548-56
references.pmid: 18005098
references.citation: Cell Host Microbe. 2012 Jun 14;11(6):563-75
references.pmid: 22704617
references.citation: Gastroenterology. 2013 Dec;145(6):1347-57
references.pmid: 23973919
references.citation: Cell. 2010 Feb 5;140(3):313-26
references.pmid: 20144757
references.citation: Mol Cell. 2014 Apr 24;54(2):224-33
references.pmid: 24766886
references.citation: Nat Immunol. 2012 Jan 29;13(3):255-63
references.pmid: 22286270
references.citation: PLoS Genet. 2013 Apr;9(4):e1003456
references.pmid: 23637626
references.citation: J Biol Chem. 2009 Nov 20;284(47):32602-9
references.pmid: 19783656
references.citation: Nat Commun. 2014 May 22;5:3920
references.pmid: 24849286
references.citation: EMBO J. 2011 Jul 22;30(16):3213-4
references.pmid: 21785408
references.citation: J Biol Chem. 2006 Apr 21;281(16):11374-83
references.pmid: 16495224
references.citation: Science. 2011 Jul 8;333(6039):228-33
references.pmid: 21617041
references.citation: J Bacteriol. 1992 Oct;174(20):6418-23
references.pmid: 1400193
references.citation: Nature. 2012 Jan 15;482(7385):414-8
references.pmid: 22246324
references.citation: Nat Commun. 2013;4:2250
references.pmid: 23907271
references.citation: Cell Death Dis. 2014 Feb 20;5:e1066
references.pmid: 24556681
references.citation: Cell Death Dis. 2014 Jul 03;5:e1315
references.pmid: 24991767
references.citation: FEMS Immunol Med Microbiol. 2008 Mar;52(2):194-201
references.pmid: 18248436
references.citation: Microbes Infect. 2014 Jul;16(7):553-61
references.pmid: 24857879
references.citation: Autophagy. 2007 Sep-Oct;3(5):452-60
references.pmid: 17534139
references.citation: Gastroenterology. 2014 Aug;147(2):528-30
references.pmid: 24953625
references.citation: J Bacteriol. 2001 Aug;183(15):4652-8
references.pmid: 11443102
references.citation: Infect Immun. 2002 Dec;70(12):7126-35
references.pmid: 12438395
references.citation: Autophagy. 2012 Nov;8(11):1590-603
references.pmid: 22863730
references.citation: PLoS Pathog. 2014 Nov 20;10(11):e1004409
references.pmid: 25412422
references.citation: Cell Microbiol. 2007 Nov;9(11):2562-70
references.pmid: 17714514
references.citation: Methods Enzymol. 2009;452:325-43
references.pmid: 19200891
references.citation: Immunology. 2011 Nov;134(3):341-8
references.pmid: 21978003
references.citation: Cell Host Microbe. 2013 Jun 12;13(6):723-34
references.pmid: 23768496
references.citation: Clin Microbiol Rev. 2013 Apr;26(2):308-41
references.pmid: 23554419
references.citation: Nature. 2013 Sep 26;501(7468):512-6
references.pmid: 24005326