title: Enhanced Actin Pedestal Formation by Enterohemorrhagic Escherichia coli O157:H7 Adapted to the Mammalian Host.
abstract: Upon intestinal colonization, enterohemorrhagic Escherichia coli (EHEC) induces epithelial cells to generate actin "pedestals" beneath bound bacteria, lesions that promote colonization. To induce pedestals, EHEC utilizes a type III secretion system to translocate into the mammalian cell bacterial effectors such as translocated intimin receptor (Tir), which localizes in the mammalian cell membrane and functions as a receptor for the bacterial outer membrane protein intimin. Whereas EHEC triggers efficient pedestal formation during mammalian infection, EHEC cultured in vitro induces pedestals on cell monolayers with relatively low efficiency. To determine whether growth within the mammalian host enhances EHEC pedestal formation, we compared in vitro-cultivated bacteria with EHEC directly isolated from infected piglets. Mammalian adaptation by EHEC was associated with a dramatic increase in the efficiency of cell attachment and pedestal formation. The amounts of intimin and Tir were significantly higher in host-adapted than in in vitro-cultivated bacteria, but increasing intimin or Tir expression, or artificially increasing the level of bacterial attachment to mammalian cells, did not enhance pedestal formation by in vitro-cultivated EHEC. Instead, a functional assay suggested that host-adapted EHEC translocate Tir much more efficiently than does in vitro-cultivated bacteria. These data suggest that adaptation of EHEC to the mammalian intestine enhances bacterial cell attachment, expression of intimin and Tir, and translocation of effectors that promote actin signaling.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School Worcester, MA, USA.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Brady
authors.forename: Padhma
authors.initials: P
authors.lastname: Radhakrishnan
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Loranne
authors.initials: L
authors.lastname: Magoun
authors.forename: Kenan C
authors.initials: KC
authors.lastname: Murphy
authors.forename: Jean
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Arthur
authors.initials: A
authors.lastname: Donohue-Rolfe
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
references.citation: Cell Microbiol. 2008 Mar;10(3):549-56
references.pmid: 18053003
references.citation: Appl Environ Microbiol. 2009 Aug;75(15):4975-83
references.pmid: 19525268
references.citation: Mol Microbiol. 1998 Oct;30(1):147-61
references.pmid: 9786192
references.citation: Mol Microbiol. 2002 Mar;43(5):1227-41
references.pmid: 11918809
references.citation: Dev Cell. 2004 Aug;7(2):217-28
references.pmid: 15296718
references.citation: Appl Environ Microbiol. 2008 Feb;74(4):1087-93
references.pmid: 18083855
references.citation: Infect Immun. 1995 Jan;63(1):301-8
references.pmid: 7806370
references.citation: Mol Microbiol. 1996 Apr;20(1):87-100
references.pmid: 8861207
references.citation: Cell. 1997 Nov 14;91(4):511-20
references.pmid: 9390560
references.citation: Mol Microbiol. 2003 May;48(3):795-809
references.pmid: 12694622
references.citation: Mol Microbiol. 2001 Dec;42(5):1269-80
references.pmid: 11886558
references.citation: Dig Dis. 1997 Jan-Apr;15(1-2):67-91
references.pmid: 9101130
references.citation: BMC Mol Biol. 2003 Dec 13;4:11
references.pmid: 14672541
references.citation: Infect Immun. 1989 Apr;57(4):1290-8
references.pmid: 2647635
references.citation: Infect Immun. 1987 Dec;55(12):3117-25
references.pmid: 3316033
references.citation: J Bacteriol. 1993 Aug;175(15):4670-80
references.pmid: 8393004
references.citation: Infect Immun. 1992 Dec;60(12):5302-6
references.pmid: 1452364
references.citation: J Biol Chem. 1996 Aug 23;271(34):20359-64
references.pmid: 8702771
references.citation: J Bacteriol. 2001 May;183(9):2823-33
references.pmid: 11292802
references.citation: Microbiology (Reading). 2007 Feb;153(Pt 2):464-473
references.pmid: 17259617
references.citation: Cell Microbiol. 2005 Aug;7(8):1163-72
references.pmid: 16008583
references.citation: PLoS One. 2011 Feb 28;6(2):e17424
references.pmid: 21387009
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1664-8
references.pmid: 7878036
references.citation: Clin Microbiol Rev. 1989 Jan;2(1):15-38
references.pmid: 2644022
references.citation: Microbes Infect. 2007 Sep;9(11):1316-24
references.pmid: 17890132
references.citation: Mol Microbiol. 1998 Jul;29(2):559-70
references.pmid: 9720872
references.citation: Mol Microbiol. 1999 Oct;34(1):67-81
references.pmid: 10540286
references.citation: J Mol Biol. 1980 Apr;138(2):179-207
references.pmid: 6997493
references.citation: Mol Biol Cell. 2011 Jul 15;22(14):2436-47
references.pmid: 21613538
references.citation: PLoS Pathog. 2010 Aug 19;6(8):e1001056
references.pmid: 20808845
references.citation: Gene. 1997 Jan 3;184(1):107-14
references.pmid: 9016959
references.citation: Infect Immun. 1996 Mar;64(3):966-73
references.pmid: 8641808
references.citation: Mol Microbiol. 2009 Aug;73(3):446-65
references.pmid: 19570135
references.citation: Nature. 2002 Jun 6;417(6889):642-5
references.pmid: 12050664
references.citation: Clin Microbiol Rev. 1998 Jan;11(1):142-201
references.pmid: 9457432
references.citation: J Bacteriol. 2009 Jan;191(1):411-21
references.pmid: 18952791
references.citation: Proc Natl Acad Sci U S A. 1990 Oct;87(20):7839-43
references.pmid: 2172966
references.citation: N Engl J Med. 1983 Mar 24;308(12):681-5
references.pmid: 6338386
references.citation: Infect Immun. 1999 May;67(5):2389-98
references.pmid: 10225900
references.citation: Trends Microbiol. 2011 May;19(5):217-24
references.pmid: 21333542
references.citation: J Bacteriol. 2008 Jan;190(1):438-41
references.pmid: 17981979
references.citation: Infect Immun. 1996 Jun;64(6):2225-33
references.pmid: 8675331
references.citation: J Clin Microbiol. 2003 Jul;41(7):3438-40
references.pmid: 12843115
references.citation: Cell Microbiol. 2000 Feb;2(1):1-9
references.pmid: 11207558
references.citation: Mol Microbiol. 2009 Oct;74(2):347-63
references.pmid: 19703108
references.citation: Cell Microbiol. 2004 Dec;6(12):1167-83
references.pmid: 15527496
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15196-201
references.pmid: 10611361
references.citation: Microbiology (Reading). 2009 Sep;155(Pt 9):2907-2918
references.pmid: 19497950
references.citation: Infect Immun. 1997 Jan;65(1):320-6
references.pmid: 8975932
references.citation: Mol Microbiol. 1997 Jan;23(2):399-407
references.pmid: 9044273
references.citation: Infect Immun. 1986 Jan;51(1):16-23
references.pmid: 3510166
references.citation: FEMS Microbiol Lett. 2006 Feb;255(2):187-202
references.pmid: 16448495
references.citation: Mol Microbiol. 1999 Feb;31(4):1229-41
references.pmid: 10096089
references.citation: Microbiology (Reading). 2010 Aug;156(Pt 8):2271-2282
references.pmid: 20488878
references.citation: Infect Immun. 1987 Feb;55(2):455-61
references.pmid: 2879796
references.citation: J Infect Dis. 2000 May;181(5):1825-9
references.pmid: 10823794
references.citation: Nat Rev Microbiol. 2006 May;4(5):358-70
references.pmid: 16582930
references.citation: J Clin Invest. 2007 Nov;117(11):3519-29
references.pmid: 17948128
references.citation: Infect Immun. 2007 Sep;75(9):4199-210
references.pmid: 17576759
references.citation: Mol Microbiol. 2010 Jan;75(2):308-23
references.pmid: 19889090
references.citation: Mol Microbiol. 2002 Sep;45(6):1557-73
references.pmid: 12354225
references.citation: Mol Microbiol. 2007 Mar;63(5):1468-81
references.pmid: 17302821
references.citation: Infect Immun. 2006 Jan;74(1):758-64
references.pmid: 16369035
references.citation: Infect Immun. 1984 Oct;46(1):251-9
references.pmid: 6148308
references.citation: Mol Microbiol. 1992 Nov;6(22):3427-37
references.pmid: 1362446
references.citation: Infect Immun. 1999 Apr;67(4):2045-9
references.pmid: 10085058
references.citation: Infect Immun. 1991 Nov;59(11):3924-9
references.pmid: 1682254
references.citation: Cell Microbiol. 2008 Apr;10(4):836-47
references.pmid: 18067584
references.citation: Infect Immun. 1996 Nov;64(11):4472-9
references.pmid: 8890194
references.citation: Infect Immun. 1995 Sep;63(9):3621-7
references.pmid: 7642299
references.citation: Curr Opin Microbiol. 2003 Feb;6(1):82-90
references.pmid: 12615225
references.citation: Appl Environ Microbiol. 2009 Sep;75(18):5779-86
references.pmid: 19633120
references.citation: FEBS J. 2010 Jun;277(11):2390-402
references.pmid: 20477869
references.citation: J Biol Chem. 2002 Jan 25;277(4):2876-85
references.pmid: 11704679