title: Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.
abstract: Bacterially induced cell death in human lymphocytes is an important virulence factor for pathogenic bacteria. Previously discovered mechanisms of bacterially induced cell death are predominantly based on the transfer of bacterial proteins to the target host cell, such as the toxins secreted through type I, II, and VI secretion systems or effector proteins injected through type III, IV, and Vb secretion systems. Here, we report a mechanism employed by the Gram-negative oral pathogen Fusobacterium nucleatum for cell death induction of human lymphocytes via two outer membrane proteins (OMPs), Fap2 and RadD, which share regions homologous to autotransporter secretion systems (type Va secretion systems). Genetic and physiological studies established that inactivation of the two OMPs led to significantly reduced ability to trigger cell death in Jurkat cells, while the corresponding double mutant was almost completely attenuated. Additional biochemical and molecular analyses demonstrated that cell-free F. nucleatum membranes are sufficient to induce cell death in Jurkat cells, suggesting that no active process or effector protein transfer was necessary to induce eukaryotic cell death.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kaplan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Ma
authors.forename: Avina
authors.initials: A
authors.lastname: Paranjpe
authors.forename: Anahid
authors.initials: A
authors.lastname: Jewett
authors.forename: Renate
authors.initials: R
authors.lastname: Lux
authors.forename: Susan
authors.initials: S
authors.lastname: Kinder-Haake
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D016967:Fusobacterium nucleatum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000821:virology*
chemical_list: D001425:Bacterial Outer Membrane Proteins
references.citation: Cancer Res. 2003 Mar 1;63(5):951-7
references.pmid: 12615708
references.citation: Infect Immun. 2002 Mar;70(3):1657-63
references.pmid: 11854262
references.citation: Nature. 1981 Dec 17;294(5842):665-7
references.pmid: 7031483
references.citation: Infect Immun. 2001 Aug;69(8):5080-7
references.pmid: 11447189
references.citation: Infect Immun. 1982 Nov;38(2):651-67
references.pmid: 7141708
references.citation: Clin Microbiol Rev. 2005 Apr;18(2):326-82
references.pmid: 15831828
references.citation: Mol Microbiol. 1993 Aug;9(4):653-60
references.pmid: 8231801
references.citation: Infect Immun. 2005 Mar;73(3):1543-52
references.pmid: 15731052
references.citation: Microbiol Mol Biol Rev. 2004 Dec;68(4):692-744
references.pmid: 15590781
references.citation: J Bacteriol. 2000 Feb;182(4):1176-80
references.pmid: 10648549
references.citation: Infect Immun. 1985 May;48(2):507-19
references.pmid: 3988344
references.citation: J Immunol. 1984 May;132(5):2357-62
references.pmid: 6715883
references.citation: Mol Microbiol. 2009 Jan;71(1):35-47
references.pmid: 19007407
references.citation: J Bioenerg Biomembr. 1990 Jun;22(3):473-91
references.pmid: 2202728
references.citation: J Periodontal Res. 1993 Jan;28(1):21-6
references.pmid: 8426279
references.citation: J Periodontol. 1988 Nov;59(11):741-9
references.pmid: 3204481
references.citation: Infect Immun. 1982 Dec;38(3):1137-48
references.pmid: 7152665
references.citation: Trends Microbiol. 2005 Dec;13(12):581-8
references.pmid: 16216510
references.citation: J Biol Chem. 1998 Dec 4;273(49):32895-900
references.pmid: 9830039
references.citation: Clin Microbiol Rev. 1996 Jan;9(1):55-71
references.pmid: 8665477
references.citation: Biochim Biophys Acta. 2005 Jul 30;1713(2):92-112
references.pmid: 15993836
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15508-13
references.pmid: 17873062
references.citation: J Dent Res. 2005 Aug;84(8):700-4
references.pmid: 16040725
references.citation: J Biol Chem. 1997 Nov 28;272(48):30463-9
references.pmid: 9374538
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1244-63
references.pmid: 9841671
references.citation: Nature. 1992 Jul 9;358(6382):167-9
references.pmid: 1614548
references.citation: J Bacteriol. 2005 Aug;187(15):5330-40
references.pmid: 16030227
references.citation: Infect Immun. 2007 Jun;75(6):2903-13
references.pmid: 17420236
references.citation: J Bacteriol. 2002 Apr;184(7):2005-18
references.pmid: 11889109
references.citation: Infect Immun. 1984 Nov;46(2):332-9
references.pmid: 6334029
references.citation: Microbiology (Reading). 2005 Jan;151(Pt 1):157-166
references.pmid: 15632435
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18578-83
references.pmid: 16339899
references.citation: Clin Microbiol Rev. 2007 Oct;20(4):535-49
references.pmid: 17934073
references.citation: Infect Immun. 1988 May;56(5):1314-9
references.pmid: 2451642
references.citation: Plasmid. 2006 Jan;55(1):27-38
references.pmid: 16115683
references.citation: Genome Res. 2003 Jun;13(6A):1180-9
references.pmid: 12799352
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4918-23
references.pmid: 16549796
references.citation: Infect Immun. 2000 Apr;68(4):1893-8
references.pmid: 10722579
references.citation: Microbes Infect. 2000 Nov;2(14):1705-19
references.pmid: 11137044
references.citation: Infect Immun. 1986 Jun;52(3):650-6
references.pmid: 3710577
references.citation: Infect Immun. 1996 Apr;64(4):1335-41
references.pmid: 8606098
references.citation: Mol Plant Microbe Interact. 2005 Sep;18(9):891-8
references.pmid: 16167759