title: The spectrin cytoskeleton is crucial for adherent and invasive bacterial pathogenesis.
abstract: Various enteric bacterial pathogens target the host cell cytoskeletal machinery as a crucial event in their pathogenesis. Despite thorough studies detailing strategies microbes use to exploit these components of the host cell, the role of the spectrin-based cytoskeleton has been largely overlooked. Here we show that the spectrin cytoskeleton is a host system that is hijacked by adherent (Entropathogenic Escherichia coli [EPEC]), invasive triggering (Salmonella enterica serovar Typhimurium [S. Typhimurium]) and invasive zippering (Listeria monocytogenes) bacteria. We demonstrate that spectrin cytoskeletal proteins are recruited to EPEC pedestals, S. Typhimurium membrane ruffles and Salmonella containing vacuoles (SCVs), as well as sites of invasion and comet tail initiation by L. monocytogenes. Spectrin was often seen co-localizing with actin filaments at the cell periphery, however a disconnect between the actin and spectrin cytoskeletons was also observed. During infections with S. Typhimurium ΔsipA, actin-rich membrane ruffles at characteristic sites of bacterial invasion often occurred in the absence of spectrin cytoskeletal proteins. Additionally, early in the formation of L. monocytogenes comet tails, spectrin cytoskeletal elements were recruited to the surface of the internalized bacteria independent of actin filaments. Further studies revealed the presence of the spectrin cytoskeleton during SCV and Listeria comet tail formation, highlighting novel cytoplasmic roles for the spectrin cytoskeleton. SiRNA targeted against spectrin and the spectrin-associated proteins severely diminished EPEC pedestal formation as well as S. Typhimurium and L. monocytogenes invasion. Ultimately, these findings identify the spectrin cytoskeleton as a ubiquitous target of enteric bacterial pathogens and indicate that this cytoskeletal system is critical for these infections to progress.
authors: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Tyson
authors: T
authors: Ruetz
authors: Steve
authors: S
authors: Cornick
authors: Julian Andrew
authors: JA
authors: Guttman
references: Cell Motil Cytoskeleton. 2009 Oct;66(10):816-23
references: 19296488
references: APMIS. 2000 Jan;108(1):45-50
references: 10698084
references: Biol Cell. 2006 May;98(5):279-93
references: 16336193
references: Am J Pathol. 1967 Jul;51(1):137-61
references: 19971038
references: PLoS One. 2010 Feb 24;5(2):e9406
references: 20195380
references: Curr Opin Microbiol. 2009 Feb;12(1):101-9
references: 19144561
references: Int J Med Microbiol. 2002 Feb;291(6-7):479-85
references: 11890547
references: Infect Immun. 2003 Jun;71(6):3310-9
references: 12761113
references: J Cell Biol. 1998 Aug 24;142(4):937-47
references: 9722607
references: Protoplasma. 2010 Aug;244(1-4):99-131
references: 20668894
references: Nat Cell Biol. 2001 Sep;3(9):856-9
references: 11533668
references: Science. 1999 Mar 26;283(5410):2092-5
references: 10092234
references: Nat Cell Biol. 2005 Sep;7(9):894-900
references: 16113677
references: Science. 2004 Apr 9;304(5668):242-8
references: 15073367
references: Curr Opin Microbiol. 2006 Feb;9(1):40-5
references: 16406772
references: Cell. 1997 Nov 14;91(4):511-20
references: 9390560
references: J Biol Chem. 2007 Jan 19;282(3):2029-37
references: 17074766
references: J Cell Biol. 1984 Jun;98(6):2055-63
references: 6144685
references: Cell Host Microbe. 2007 Nov 15;2(5):340-51
references: 18005755
references: EMBO J. 2001 Mar 15;20(6):1245-58
references: 11250891
references: Mol Microbiol. 2001 Sep;41(6):1445-58
references: 11580847
references: Trends Cell Biol. 2003 Jan;13(1):23-31
references: 12480337
references: Microbes Infect. 2009 Sep;11(10-11):850-8
references: 19450704
references: Pharm Res. 1997 Dec;14(12):1835-7
references: 9453077
references: Mol Microbiol. 2000 Jun;36(6):1206-21
references: 10931274
references: Physiol Rev. 2001 Jul;81(3):1353-92
references: 11427698
references: J Cell Sci. 2005 Apr 1;118(Pt 7):1537-47
references: 15769844
references: Mol Microbiol. 1997 Sep;25(5):903-12
references: 9364916
references: Am J Physiol. 1996 May;270(5 Pt 1):C1263-70
references: 8967424
references: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7996-8000
references: 7644527
references: Anat Rec (Hoboken). 2007 Feb;290(2):199-205
references: 17441212
references: Infect Immun. 2010 Aug;78(8):3316-22
references: 20515931
references: Infect Immun. 2002 Mar;70(3):1087-96
references: 11854187
references: Curr Opin Microbiol. 2008 Feb;11(1):38-45
references: 18304858
references: J Cell Biol. 1986 Nov;103(5):1751-65
references: 3023391
references: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2574-9
references: 9482928
references: Biochem Soc Trans. 2009 Aug;37(Pt 4):796-803
references: 19614597
references: J Cell Sci. 1993 Jul;105 ( Pt 3):699-710
references: 8408297
references: J Biol Chem. 1999 Dec 10;274(50):35908-13
references: 10585476
references: Science. 2003 Sep 26;301(5641):1918-21
references: 14512630
references: Trends Cell Biol. 2008 May;18(5):220-7
references: 18396046
references: Cell Motil Cytoskeleton. 1998;41(1):74-86
references: 9744301