title: The Legionella pneumophila effector protein, LegC7, alters yeast endosomal trafficking.
abstract: The intracellular pathogen, Legionella pneumophila, relies on numerous secreted effector proteins to manipulate host endomembrane trafficking events during pathogenesis, thereby preventing fusion of the bacteria-laden phagosome with host endolysosomal compartments, and thus escaping degradation. Upon expression in the surrogate eukaryotic model Saccharomyces cerevisiae, we find that the L. pneumophila LegC7/YlfA effector protein disrupts the delivery of both biosynthetic and endocytic cargo to the yeast vacuole. We demonstrate that the effects of LegC7 are specific to the endosome:vacuole delivery pathways; LegC7 expression does not disrupt other known vacuole-directed pathways. Deletions of the ESCRT-0 complex member, VPS27, provide resistance to the LegC7 toxicity, providing a possible target for LegC7 function in vivo. Furthermore, a single amino acid substitution in LegC7 abrogates both its toxicity and ability to alter endosomal traffic in vivo, thereby identifying a critical functional domain. LegC7 likely inhibits endosomal trafficking during L. pneumophila pathogenesis to prevent entry of the phagosome into the endosomal maturation pathway and eventual fusion with the lysosome.
authors: Department of Microbiology, University of Georgia, Athens, Georgia, Unites States of America.
authors: Kevin M
authors: KM
authors: O'Brien
authors: Department of Microbiology, University of Georgia, Athens, Georgia, Unites States of America.
authors: Elizabeth L
authors: EL
authors: Lindsay
authors: Department of Microbiology, University of Georgia, Athens, Georgia, Unites States of America; Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
authors: Vincent J
authors: VJ
authors: Starai
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000172:deficiency / Q000235:genetics; D011992:Endosomes / Q000378:metabolism*; D017353:Gene Deletion; D016952:Legionella pneumophila; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014617:Vacuoles / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C119627:VPS27 protein, S cerevisiae
references: Mol Cell Biol. 1988 Nov;8(11):4936-48
references: 3062374
references: EMBO J. 1989 Jul;8(7):2057-65
references: 2676511
references: J Cell Biol. 1992 Oct;119(2):287-99
references: 1400574
references: Mol Biol Cell. 1992 Dec;3(12):1389-402
references: 1493335
references: J Cell Biol. 1994 Apr;125(2):283-98
references: 8163546
references: EMBO J. 1994 Jul 15;13(14):3261-71
references: 8045256
references: J Cell Biol. 1995 Mar;128(5):779-92
references: 7533169
references: Infect Immun. 1995 Sep;63(9):3609-20
references: 7642298
references: EMBO J. 1997 May 15;16(10):2769-82
references: 9184222
references: Yeast. 1998 Jan 30;14(2):115-32
references: 9483801
references: J Cell Biol. 1998 Aug 24;142(4):913-22
references: 9722605
references: J Cell Biol. 1998 Aug 24;142(4):949-61
references: 9722608
references: Cell. 1998 Dec 11;95(6):847-58
references: 9865702
references: Mol Microbiol. 2005 May;56(4):918-33
references: 15853880
references: J Bacteriol. 2005 Nov;187(22):7716-26
references: 16267296
references: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13004-9
references: 16916930
references: J Cell Biol. 2006 Dec 4;175(5):715-20
references: 17130288
references: Mol Biol Cell. 2007 Feb;18(2):697-706
references: 17182850
references: Dev Cell. 2007 Jun;12(6):973-86
references: 17543868
references: PLoS One. 2007;2(10):e1078
references: 17957260
references: J Cell Sci. 2007 Nov 1;120(Pt 21):3729-37
references: 17959629
references: Mol Biol Cell. 2008 Jul;19(7):2936-48
references: 18448668
references: PLoS Pathog. 2008;4(8):e1000117
references: 18670632
references: Cell Microbiol. 2009 Feb;11(2):230-48
references: 19016775
references: J Exp Med. 1983 Dec 1;158(6):2108-26
references: 6644240
references: Cell. 1985 Apr;40(4):1001-9
references: 3886157
references: Infect Immun. 1986 Sep;53(3):553-9
references: 3744550
references: Structure. 2009 Mar 11;17(3):406-16
references: 19278655
references: PLoS Pathog. 2009 Jul;5(7):e1000508
references: 19593377
references: PLoS One. 2009;4(10):e7375
references: 19823575
references: Traffic. 2010 Sep;11(9):1141-50
references: 20626707
references: EMBO J. 2011 Aug 31;30(17):3481-500
references: 21878991
references: J Bacteriol. 2012 Mar;194(6):1389-400
references: 22228731
references: PLoS Pathog. 2012;8(12):e1003082
references: 23271971
references: Traffic. 2012 Apr;13(4):586-98
references: 22212814
references: Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E707-15
references: 23382224
references: PLoS One. 2013;8(2):e56798
references: 23437241
references: Genetics. 2013 Jun;194(2):341-61
references: 23733851
references: FEBS J. 2013 Jun;280(12):2743-57
references: 23351085
references: Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):436-41
references: 24531477
references: Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4560-5
references: 24616501
references: Crit Rev Biochem Mol Biol. 2014 May-Jun;49(3):242-61
references: 24456136
references: Am J Epidemiol. 1981 Sep;114(3):337-47
references: 7304569
references: Mol Cell. 2001 Jun;7(6):1131-41
references: 11430817
references: J Biol Chem. 2001 Aug 3;276(31):29210-7
references: 11382752
references: EMBO J. 2001 Aug 1;20(15):4035-40
references: 11483507
references: J Cell Sci. 2001 Jun;114(Pt 12):2255-63
references: 11493665
references: Cell. 2001 Jul 27;106(2):145-55
references: 11511343
references: J Cell Sci. 2001 Dec;114(Pt 24):4637-50
references: 11792828
references: Cell. 2002 Feb 8;108(3):357-69
references: 11853670
references: J Cell Biol. 2003 Feb 3;160(3):365-74
references: 12566429
references: J Exp Med. 2004 May 3;199(9):1201-11
references: 15117975
references: J Cell Biol. 1975 Jul;66(1):188-93
references: 49354
references: N Engl J Med. 1977 Dec 1;297(22):1197-203
references: 335245
references: Appl Environ Microbiol. 1981 Jan;41(1):9-16
references: 7013702
references: J Biol Chem. 2003 Apr 4;278(14):12513-21
references: 12551915
references: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7626-31
references: 12802020
references: Yeast. 2003 Aug;20(11):985-93
references: 12898713
references: Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):841-6
references: 14715899
references: Science. 2004 Feb 27;303(5662):1358-61
references: 14988561