title: Proteolytic processing of the Yersinia pestis YapG autotransporter by the omptin protease Pla and the contribution of YapG to murine plague pathogenesis.
abstract: Autotransporter protein secretion represents one of the simplest forms of secretion across Gram-negative bacterial membranes. Once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. Autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. To better understand the role of autotransporters in disease, our research focused on the autotransporters of Yersinia pestis, the aetiological agent of plague. Y. pestis strain CO92 has nine functional conventional autotransporters, referred to as Yaps for Yersinia autotransporter proteins. Three Yaps have been directly implicated in virulence using established mouse models of plague infection (YapE, YapJ and YapK). Whilst previous studies from our laboratory have shown that most of the CO92 Yaps are cell associated, YapE and YapG are processed and released by the omptin protease Pla. In this study, we identified the Pla cleavage sites in YapG that result in many released forms of YapG in Y. pestis, but not in the evolutionarily related gastrointestinal pathogen, Yersinia pseudotuberculosis, which lacks Pla. Furthermore, we showed that YapG does not contribute to Y. pestis virulence in established mouse models of bubonic and pneumonic infection. As Y. pestis has a complex life cycle involving a wide range of mammalian hosts and a flea vector for transmission, it remains to be elucidated whether YapG has a measurable role in any other stage of plague disease.
authors: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: M Chelsea
authors: MC
authors: Lane
authors: Department of Molecular Microbiology, Washington University, St Louis, MO 63110, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.|Division of Biology and Biomedical Sciences, Washington University, St Louis, MO 63110, USA.
authors: Jonathan D
authors: JD
authors: Lenz
authors: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Virginia L
authors: VL
authors: Miller
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D010930:Plague / Q000382:microbiology*; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors; D015010:Yersinia pestis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D037521:Virulence Factors; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; C057840:omptin outer membrane protease
references: J Mol Med (Berl). 1997 Sep;75(9):645-52
references: 9351703
references: Annu Rev Microbiol. 2007;61:89-112
references: 17506669
references: J Bacteriol. 2004 Mar;186(5):1249-57
references: 14973035
references: Mol Microbiol. 2001 Jun;40(5):1097-111
references: 11401715
references: Gut Microbes. 2010 Sep;1(5):339-344
references: 21327044
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references: 10829079
references: J Bacteriol. 2004 May;186(9):2724-34
references: 15090514
references: Infect Immun. 2007 Jul;75(7):3233-44
references: 17420234
references: PLoS Pathog. 2011 Feb;7(2):e1001298
references: 21383970
references: J Bacteriol. 2009 Nov;191(21):6571-83
references: 19734313
references: Infect Immun. 2010 Nov;78(11):4882-94
references: 20805336
references: J Bacteriol. 2012 Nov;194(21):5769-82
references: 22904291
references: J Bacteriol. 2011 Nov;193(21):5936-49
references: 21873491
references: Infect Immun. 2010 Apr;78(4):1659-69
references: 20145097
references: Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13514-9
references: 16938880
references: PLoS Pathog. 2010 Jul 22;6(7):e1001010
references: 20661475
references: Mol Microbiol. 2005 Jul;57(1):196-211
references: 15948960
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D302-5
references: 22053084
references: Infect Immun. 1982 Aug;37(2):506-12
references: 6749681
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references: 19920124
references: Am J Pathol. 2005 May;166(5):1427-39
references: 15855643
references: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13826-31
references: 15358858
references: Vector Borne Zoonotic Dis. 2010 Oct;10(8):749-56
references: 20055582
references: Plasmid. 2012 Jul;68(1):33-42
references: 22445322
references: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17786-91
references: 16306265
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D225-9
references: 21109532
references: Cold Spring Harb Protoc. 2018 Mar 1;2018(3):
references: 29496819
references: J Bacteriol. 2009 Aug;191(16):5169-79
references: 19525348
references: Infect Immun. 2012 Oct;80(10):3693-705
references: 22802344
references: Infect Immun. 2004 Oct;72(10):5919-24
references: 15385494
references: J Bacteriol. 1961 Apr;81:605-8
references: 13714203
references: Science. 2007 Jan 26;315(5811):509-13
references: 17255510
references: Microbes Infect. 1999 Apr;1(4):323-33
references: 10602666
references: Trends Microbiol. 1998 Sep;6(9):370-8
references: 9778731
references: Nat Rev Microbiol. 2003 Oct;1(1):55-64
references: 15040180
references: Clin Lab Med. 1999 Sep;19(3):523-36, vi
references: 10549424
references: Bioorg Med Chem Lett. 2008 Jan 1;18(1):427-31
references: 17981463
references: Infect Immun. 1989 May;57(5):1517-23
references: 2651310
references: J Bacteriol. 2008 Jun;190(12):4147-61
references: 18424525
references: J Biol Chem. 2011 Aug 26;286(34):29771-9
references: 21757737
references: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5526-30
references: 16567636
references: Microbiology (Reading). 2009 Dec;155(Pt 12):3982-3991
references: 19815580
references: Infect Immun. 2012 Jan;80(1):321-32
references: 21930758
references: Adv Exp Med Biol. 2007;603:268-78
references: 17966423
references: Microbiology (Reading). 2008 Jun;154(Pt 6):1802-1812
references: 18524935
references: Microbiol Mol Biol Rev. 2004 Dec;68(4):692-744
references: 15590781
references: Nature. 2001 Oct 4;413(6855):523-7
references: 11586360
references: Infect Immun. 2001 Mar;69(3):1231-43
references: 11179284
references: Clin Microbiol Rev. 1997 Jan;10(1):35-66
references: 8993858
references: Bioinformatics. 2001 Sep;17(9):847-8
references: 11590104
references: Annu Rev Microbiol. 2005;59:69-89
references: 15847602
references: J Bacteriol. 2004 Sep;186(17):5919-25
references: 15317797
references: Microbiology (Reading). 2007 Jul;153(Pt 7):2321-2331
references: 17600076
references: Mol Microbiol. 2008 May;68(4):997-1017
references: 18430084
references: J Infect Dis. 1958 Sep-Oct;103(2):183-7
references: 13588071
references: FEMS Microbiol Rev. 2001 Dec;25(5):531-52
references: 11742690
references: Infect Immun. 2009 Jan;77(1):317-26
references: 18936182
references: Microb Pathog. 2011 Sep;51(3):169-77
references: 21554944
references: Am J Clin Pathol. 2003 Jun;119 Suppl:S78-85
references: 12951845
references: Infect Immun. 1981 Feb;31(2):839-41
references: 7216478
references: Microbiology (Reading). 1996 Dec;142 ( Pt 12):3415-24
references: 9004504
references: Infect Immun. 2011 Dec;79(12):4753-63
references: 21911462
references: J Biol Chem. 2010 Dec 17;285(51):39682-90
references: 20959450
references: Am J Trop Med Hyg. 1994 Jul;51(1):109-14
references: 8059908
references: J Bacteriol. 2004 Jul;186(13):4056-66
references: 15205407
references: J Bacteriol. 2008 Feb;190(3):1054-63
references: 18055599