title: The phage shock protein PspA facilitates divalent metal transport and is required for virulence of Salmonella enterica sv. Typhimurium.
abstract: The phage shock protein (Psp) system is induced by extracytoplasmic stress and thought to be important for the maintenance of proton motive force. We investigated the contribution of PspA to Salmonella virulence. A pspA deletion mutation significantly attenuates the virulence of Salmonella enterica serovar Typhimurium following intraperitoneal inoculation of C3H/HeN (Ity(r) ) mice. PspA was found to be specifically required for virulence in mice expressing the natural resistance-associated macrophage protein 1 (Nramp1) (Slc11a1) divalent metal transporter, which restricts microbial growth by limiting the availability of essential divalent metals within the phagosome. Salmonella competes with Nramp1 by expressing multiple metal uptake systems including the Nramp-homologue MntH, the ABC transporter SitABCD and the ZIP family transporter ZupT. PspA was found to facilitate Mn(2+) transport by MntH and SitABCD, as well as Zn(2+) and Mn(2+) transport by ZupT. In vitro uptake of (54) Mn(2+) by MntH and ZupT was reduced in the absence of PspA. Transport-deficient mutants exhibit reduced viability in the absence of PspA when grown under metal-limited conditions. Moreover, the ZupT transporter is required for Salmonella enterica serovar Typhimurium virulence in Nramp1-expressing mice. We propose that PspA promotes Salmonella virulence by maintaining proton motive force, which is required for the function of multiple transporters mediating bacterial divalent metal acquisition during infection.
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Karlinsey
authors.forename: Michael E
authors.initials: ME
authors.lastname: Maguire
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Becker
authors.forename: Marie-Laure V
authors.initials: ML
authors.lastname: Crouch
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence; D015032:Zinc / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D006360:Heat-Shock Proteins; D007501:Iron; D008345:Manganese; D026901:Membrane Transport Proteins; D015032:Zinc; D000099173:Natural Resistance-associated Macrophage Protein 1; C069816:phage shock protein, Bacteria
references.citation: Mol Microbiol. 2003 May;48(4):1131-43
references.pmid: 12753201
references.citation: Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2191-5
references.pmid: 8134371
references.citation: Mol Microbiol. 2005 May;56(3):811-23
references.pmid: 15819634
references.citation: J Bacteriol. 2002 Feb;184(3):864-6
references.pmid: 11790762
references.citation: Annu Rev Cell Biol. 1992;8:67-113
references.pmid: 1282354
references.citation: Mol Microbiol. 2004 Nov;54(3):823-35
references.pmid: 15491370
references.citation: Infect Immun. 2005 Jan;73(1):88-102
references.pmid: 15618144
references.citation: J Exp Med. 2000 Nov 6;192(9):1237-48
references.pmid: 11067873
references.citation: J Bacteriol. 2002 Jun;184(12):3159-66
references.pmid: 12029031
references.citation: J Bacteriol. 2005 Mar;187(5):1604-11
references.pmid: 15716430
references.citation: Nature. 2008 Jan 24;451(7177):489-92
references.pmid: 18216859
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 15;10(5):489-95
references.pmid: 8548327
references.citation: J Biol Chem. 2004 Dec 31;279(53):55707-14
references.pmid: 15485810
references.citation: Annu Rev Biochem. 2004;73:241-68
references.pmid: 15189142
references.citation: Microbiology (Reading). 2003 Sep;149(Pt 9):2385-2396
references.pmid: 12949164
references.citation: Mol Microbiol. 2004 Jan;51(2):483-95
references.pmid: 14756788
references.citation: Mol Microbiol. 2005 Aug;57(3):621-8
references.pmid: 16045608
references.citation: J Ind Microbiol Biotechnol. 2005 Jun;32(6):215-26
references.pmid: 15889311
references.citation: Infect Immun. 2008 Mar;76(3):1024-35
references.pmid: 18160484
references.citation: Nat Rev Microbiol. 2006 May;4(5):383-94
references.pmid: 16715050
references.citation: Genomics. 1994 Sep 1;23(1):51-61
references.pmid: 7829102
references.citation: Infect Immun. 2009 Mar;77(3):1155-64
references.pmid: 19103764
references.citation: Mol Microbiol. 2002 Sep;45(6):1599-611
references.pmid: 12354228
references.citation: Infect Immun. 2005 Jan;73(1):459-63
references.pmid: 15618185
references.citation: Mol Microbiol. 2004 Apr;52(1):169-87
references.pmid: 15049819
references.citation: Biochim Biophys Acta. 2000 May 1;1465(1-2):190-8
references.pmid: 10748254
references.citation: Mol Microbiol. 1997 Apr;24(2):255-61
references.pmid: 9159513
references.citation: J Infect Dis. 1976 Jan;133(1):72-8
references.pmid: 1107437
references.citation: Clin Exp Immunol. 1977 Oct;30(1):130-40
references.pmid: 606434
references.citation: J Bacteriol. 1996 Apr;178(7):1936-45
references.pmid: 8606168
references.citation: Mol Microbiol. 2005 May;56(3):789-99
references.pmid: 15819632
references.citation: Biochim Biophys Acta. 2004 Nov 11;1694(1-3):121-34
references.pmid: 15546662
references.citation: J Bacteriol. 2004 Jul;186(13):4199-208
references.pmid: 15205422
references.citation: Curr Opin Microbiol. 1999 Apr;2(2):159-65
references.pmid: 10322173
references.citation: Annu Rev Biophys Biophys Chem. 1990;19:7-41
references.pmid: 2141983
references.citation: Mol Microbiol. 2000 Mar;35(5):1146-55
references.pmid: 10712695
references.citation: Mol Microbiol. 2000 Jun;36(5):1085-100
references.pmid: 10844693
references.citation: Curr Opin Microbiol. 2004 Apr;7(2):157-62
references.pmid: 15063853
references.citation: Infect Immun. 1999 Mar;67(3):1386-92
references.pmid: 10024586
references.citation: Cell Microbiol. 2001 Dec;3(12):773-84
references.pmid: 11736990
references.citation: J Biol Chem. 2007 Dec 7;282(49):35646-56
references.pmid: 17932044
references.citation: Infect Immun. 2002 Aug;70(8):4721-5
references.pmid: 12117991
references.citation: J Exp Med. 1997 Feb 17;185(4):717-30
references.pmid: 9034150
references.citation: Proc Natl Acad Sci U S A. 1990 Feb;87(3):862-6
references.pmid: 2105503
references.citation: Biochem J. 2001 Mar 15;354(Pt 3):511-9
references.pmid: 11237855
references.citation: Microbes Infect. 2001 Jun;3(7):549-59
references.pmid: 11418329
references.citation: J Biol Chem. 2004 Jan 30;279(5):3318-26
references.pmid: 14607838
references.citation: J Leukoc Biol. 2001 Jan;69(1):43-9
references.pmid: 11200066
references.citation: Curr Opin Microbiol. 2005 Apr;8(2):122-6
references.pmid: 15802241
references.citation: Mol Microbiol. 2000 Mar;35(5):1065-78
references.pmid: 10712688
references.citation: Mol Microbiol. 2005 Jun;56(5):1119-28
references.pmid: 15882407
references.citation: Infect Immun. 2004 Jul;72(7):4004-9
references.pmid: 15213145
references.citation: Biochim Biophys Acta. 2006 Jul;1763(7):609-20
references.pmid: 16908340
references.citation: J Bacteriol. 1973 Jan;113(1):105-13
references.pmid: 4567134
references.citation: Infect Immun. 2001 Oct;69(10):6463-74
references.pmid: 11553591
references.citation: Immunobiology. 2007;212(9-10):751-7
references.pmid: 18086376
references.citation: J Bacteriol. 2003 Nov;185(22):6707-11
references.pmid: 14594846
references.citation: Methods Enzymol. 2007;421:199-209
references.pmid: 17352924
references.citation: J Exp Med. 2006 Oct 2;203(10):2363-75
references.pmid: 17000865
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references.pmid: 10829079
references.citation: J Immunol. 1981 Dec;127(6):2417-21
references.pmid: 6795274
references.citation: Pflugers Arch. 2004 Feb;447(5):571-9
references.pmid: 14530973
references.citation: Cell Microbiol. 2009 Sep;11(9):1365-81
references.pmid: 19500110
references.citation: Infect Immun. 1999 Apr;67(4):1974-81
references.pmid: 10085045
references.citation: J Membr Biol. 1998 Nov 1;166(1):1-7
references.pmid: 9784581
references.citation: Infect Immun. 2004 Sep;72(9):5522-5
references.pmid: 15322058
references.citation: Genomics Proteomics Bioinformatics. 2006 Feb;4(1):1-9
references.pmid: 16689696
references.citation: Mol Microbiol. 2002 Feb;43(3):771-82
references.pmid: 11929531
references.citation: Blood. 2003 Sep 1;102(5):1884-92
references.pmid: 12750164
references.citation: Mol Microbiol. 1999 Apr;32(1):51-62
references.pmid: 10216859
references.citation: Infect Immun. 2004 Aug;72(8):4654-61
references.pmid: 15271926
references.citation: Mol Microbiol. 2004 May;52(3):613-9
references.pmid: 15101969
references.citation: J Bacteriol. 2003 Feb;185(4):1174-80
references.pmid: 12562786
references.citation: Trends Microbiol. 2001 Aug;9(8):397-403
references.pmid: 11514223
references.citation: Mol Microbiol. 2005 May;56(4):1004-16
references.pmid: 15853886
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11008-13
references.pmid: 10984518
references.citation: EMBO J. 2006 Nov 15;25(22):5241-9
references.pmid: 17082772
references.citation: Infect Immun. 2007 Aug;75(8):3913-24
references.pmid: 17517869
references.citation: Cell Mol Life Sci. 2004 Nov;61(22):2812-26
references.pmid: 15558211
references.citation: Annu Rev Microbiol. 2001;55:591-624
references.pmid: 11544368
references.citation: Infect Immun. 1996 Aug;64(8):2923-9
references.pmid: 8757814
references.citation: Mol Microbiol. 2007 Jul;65(2):477-93
references.pmid: 17630976
references.citation: EMBO J. 1996 Jan 2;15(1):162-71
references.pmid: 8598199
references.citation: Mol Microbiol. 2004 Feb;51(3):659-74
references.pmid: 14731270
references.citation: Nature. 2008 Jan 24;451(7177):485-8
references.pmid: 18216858
references.citation: J Bacteriol. 2000 Jan;182(2):311-9
references.pmid: 10629175
references.citation: Infect Immun. 2002 Nov;70(11):6032-42
references.pmid: 12379679
references.citation: FEBS Lett. 2008 Oct 29;582(25-26):3585-9
references.pmid: 18789328
references.citation: Microbes Infect. 2001 Nov-Dec;3(14-15):1281-91
references.pmid: 11755416
references.citation: Microbes Infect. 2007 Nov-Dec;9(14-15):1662-70
references.pmid: 18024118
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(16):6383-7
references.pmid: 2548211
references.citation: Mol Microbiol. 1995 Jul;17(1):169-81
references.pmid: 7476203
references.citation: Mol Microbiol. 2003 Jan;47(1):103-18
references.pmid: 12492857
references.citation: Mol Microbiol. 2001 Jan;39(2):429-44
references.pmid: 11136463
references.citation: J Leukoc Biol. 1999 Nov;66(5):757-62
references.pmid: 10577506
references.citation: J Leukoc Biol. 1999 Jul;66(1):113-9
references.pmid: 10410998
references.citation: Methods Mol Biol. 2007;394:289-305
references.pmid: 18363241
references.citation: Genes Dev. 1997 Aug 1;11(15):2012-21
references.pmid: 9271123
references.citation: Infect Immun. 1999 Apr;67(4):1560-8
references.pmid: 10084987
references.citation: Mol Microbiol. 2007 Oct;66(1):100-9
references.pmid: 17725563
references.citation: Biochem J. 2002 Apr 1;363(Pt 1):89-94
references.pmid: 11903051
references.citation: J Mol Biol. 1991 Jul 5;220(1):35-48
references.pmid: 1712397
references.citation: Annu Rev Microbiol. 2006;60:187-209
references.pmid: 16704341
references.citation: Microbiology (Reading). 1998 Feb;144 ( Pt 2):353-359
references.pmid: 9493373
references.citation: Mol Microbiol. 2009 Mar;71(5):1228-38
references.pmid: 19170886
references.citation: Mol Microbiol. 2008 Mar;67(5):971-83
references.pmid: 18194158
references.citation: DNA. 1984 Dec;3(6):437-47
references.pmid: 6096099