title: ActA promotes Listeria monocytogenes aggregation, intestinal colonization and carriage.
abstract: Listeria monocytogenes (Lm) is a ubiquitous bacterium able to survive and thrive within the environment and readily colonizes a wide range of substrates, often as a biofilm. It is also a facultative intracellular pathogen, which actively invades diverse hosts and induces listeriosis. So far, these two complementary facets of Lm biology have been studied independently. Here we demonstrate that the major Lm virulence determinant ActA, a PrfA-regulated gene product enabling actin polymerization and thereby promoting its intracellular motility and cell-to-cell spread, is critical for bacterial aggregation and biofilm formation. We show that ActA mediates Lm aggregation via direct ActA-ActA interactions and that the ActA C-terminal region, which is not involved in actin polymerization, is essential for aggregation in vitro. In mice permissive to orally-acquired listeriosis, ActA-mediated Lm aggregation is not observed in infected tissues but occurs in the gut lumen. Strikingly, ActA-dependent aggregating bacteria exhibit an increased ability to persist within the cecum and colon lumen of mice, and are shed in the feces three order of magnitude more efficiently and for twice as long than bacteria unable to aggregate. In conclusion, this study identifies a novel function for ActA and illustrates that in addition to contributing to its dissemination within the host, ActA plays a key role in Lm persistence within the host and in transmission from the host back to the environment.
authors: Biology of Infection Unit, Institut Pasteur, Paris, France.
authors: Laetitia
authors: L
authors: Travier
authors: Stéphanie
authors: S
authors: Guadagnini
authors: Edith
authors: E
authors: Gouin
authors: Alexandre
authors: A
authors: Dufour
authors: Viviane
authors: V
authors: Chenal-Francisque
authors: Pascale
authors: P
authors: Cossart
authors: Jean-Christophe
authors: JC
authors: Olivo-Marin
authors: Jean-Marc
authors: JM
authors: Ghigo
authors: Olivier
authors: O
authors: Disson
authors: Marc
authors: M
authors: Lecuit
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002432:Cecum / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D003106:Colon / Q000378:metabolism* / Q000382:microbiology; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D008089:Listeria monocytogenes / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D037521:Virulence Factors; C072980:actA protein, Listeria monocytogenes
references: Microbiology (Reading). 2010 Dec;156(Pt 12):3782-3790
references: 20724383
references: FEMS Microbiol Lett. 2007 Sep;274(2):163-72
references: 17610513
references: Curr Biol. 1995 May 1;5(5):517-25
references: 7583101
references: Nature. 2009 Jun 18;459(7249):950-6
references: 19448609
references: Mol Microbiol. 1997 Jul;25(2):285-94
references: 9282740
references: Biochemistry. 2001 Sep 25;40(38):11390-404
references: 11560487
references: Appl Environ Microbiol. 2007 Oct;73(19):6125-33
references: 17675424
references: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17333-8
references: 20855622
references: Cell. 1992 Feb 7;68(3):521-31
references: 1739966
references: J Exp Med. 2011 Oct 24;208(11):2263-77
references: 21967767
references: Annu Rev Microbiol. 1995;49:711-45
references: 8561477
references: Appl Environ Microbiol. 2010 May;76(10):3391-7
references: 20348313
references: J Bacteriol. 2002 Feb;184(3):621-8
references: 11790730
references: Appl Environ Microbiol. 2010 Dec;76(23):7854-60
references: 20889779
references: EMBO J. 1997 Apr 1;16(7):1531-40
references: 9130698
references: Mol Microbiol. 1991 Sep;5(9):2273-83
references: 1662763
references: Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):183-93
references: 19309566
references: Science. 2001 Jun 1;292(5522):1722-5
references: 11387478
references: Mol Microbiol. 2005 Apr;56(2):383-96
references: 15813732
references: Cell. 1994 Feb 11;76(3):505-17
references: 8313471
references: Infect Immun. 2006 Jan;74(1):765-8
references: 16369036
references: Curr Opin Microbiol. 2011 Apr;14(2):118-27
references: 21388862
references: J Biol Chem. 1999 Nov 19;274(47):33616-26
references: 10559250
references: Cell. 1991 Jun 28;65(7):1127-41
references: 1905979
references: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19484-91
references: 22114192
references: Curr Microbiol. 2011 Aug;63(2):186-92
references: 21656247
references: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6152-7
references: 15073336
references: Crit Rev Microbiol. 2012 Feb;38(1):17-29
references: 21995731
references: Science. 2001 Oct 26;294(5543):849-52
references: 11679669
references: J Bacteriol. 1992 Feb;174(3):947-52
references: 1732227
references: EMBO J. 2011 Aug 12;30(18):3864-74
references: 21841773
references: Appl Environ Microbiol. 1992 Feb;58(2):765-8
references: 1610204
references: Appl Environ Microbiol. 2004 Nov;70(11):6887-91
references: 15528558
references: J Cell Biol. 2000 Aug 7;150(3):527-38
references: 10931865
references: Appl Environ Microbiol. 2006 Apr;72(4):2644-50
references: 16597969
references: Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10034-9
references: 9294158
references: Infection. 1988;16 Suppl 2:S149-56
references: 3138189
references: Epidemiol Infect. 1991 Feb;106(1):157-66
references: 1993449
references: Infect Immun. 1998 Sep;66(9):4461-8
references: 9712801
references: Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16684-9
references: 23012479
references: EMBO J. 1995 Apr 3;14(7):1314-21
references: 7729410
references: Nature. 2008 Oct 23;455(7216):1114-8
references: 18806773
references: Infect Immun. 2012 Feb;80(2):720-32
references: 22083714
references: Mol Microbiol. 1995 Apr;16(2):251-61
references: 7565087
references: Cell Microbiol. 2005 Dec;7(12):1697-706
references: 16309456
references: Infect Immun. 2006 Mar;74(3):1819-27
references: 16495556
references: Mol Microbiol. 1995 Nov;18(3):413-23
references: 8748026
references: Mol Microbiol. 1994 Mar;11(6):1141-50
references: 8022283
references: Int J Food Microbiol. 2010 Jan 31;137(1):100-5
references: 19913932
references: Poult Sci. 2006 Jun;85(6):960-73
references: 16776463
references: Infect Immun. 1989 Nov;57(11):3629-36
references: 2509366
references: Eur J Clin Microbiol Infect Dis. 2003 Jan;22(1):16-20
references: 12582739
references: Nat Protoc. 2009;4(6):799-810
references: 19444238
references: J Bacteriol. 2000 Sep;182(17):4789-96
references: 10940019
references: Mol Microbiol. 1995 Nov;18(3):425-36
references: 8748027
references: Appl Environ Microbiol. 2010 Jun;76(11):3625-36
references: 20363781
references: Nat Cell Biol. 2009 Oct;11(10):1233-40
references: 19749745
references: Infect Immun. 1995 Jul;63(7):2729-37
references: 7790091
references: Science. 1998 Jul 3;281(5373):105-8
references: 9651243
references: Int J Food Microbiol. 2011 Jan 31;145(1):1-8
references: 21276634
references: Foodborne Pathog Dis. 2006 Winter;3(4):319-36
references: 17199514
references: J Cell Biol. 1996 Nov;135(3):647-60
references: 8909540
references: J Bacteriol. 2002 Aug;184(15):4177-86
references: 12107135
references: Appl Environ Microbiol. 2010 Mar;76(6):1992-5
references: 20097825
references: Foodborne Pathog Dis. 2011 Apr;8(4):465-87
references: 21117940
references: J Cell Sci. 1993 Jul;105 ( Pt 3):699-710
references: 8408297
references: Cell Microbiol. 2001 Dec;3(12):853-64
references: 11736996
references: PLoS Pathog. 2006 Jan;2(1):e3
references: 16446782
references: J Cell Sci. 2000 Sep;113 ( Pt 18):3277-87
references: 10954425
references: Philos Trans R Soc Lond B Biol Sci. 2009 Sep 27;364(1530):2709-23
references: 19687040
references: EMBO J. 1995 Jun 15;14(12):2731-44
references: 7796802
references: J Bacteriol. 2010 Aug;192(15):3969-76
references: 20511507
references: J Biol Chem. 2007 May 18;282(20):15065-72
references: 17389602
references: Nat Rev Microbiol. 2008 Dec;6(12):904-12
references: 19008890