Effector functions of pathogenic Yersinia species

Martin Aepfelbacher; Claudia Trasak; Klaus Ruckdeschel

doi:10.1160/TH07-03-0173

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(03): 521-529
DOI: 10.1160/TH07-03-0173

Theme Issue Article

Schattauer GmbH

Effector functions of pathogenic Yersinia species

Martin Aepfelbacher

¹Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Diagnostikzentrum, Universitätsklinikum Eppendorf, Hamburg, Germany

,

Claudia Trasak

¹Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Diagnostikzentrum, Universitätsklinikum Eppendorf, Hamburg, Germany

,

Klaus Ruckdeschel

¹Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Diagnostikzentrum, Universitätsklinikum Eppendorf, Hamburg, Germany

› Author Affiliations

Abstract

Summary

Pathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins;Yops) into immune cells.Yops often exert unique biochemical activities for modulating the activity of Rho GTP-binding proteins, focal adhesion proteins, inflammatory pathways and cell survival/apoptosis. In this review we will put emphasis on the biochemistry, cell- and infection biology ofYersinia effector Yops.

Keywords

Yersinia - Yops - Rho GTPases - signalling - anti-inflammation - apoptosis

Full Text

References

References
1 Cornelis GR, Boland A, Boyd AP. et al. The virulence plasmid of Yersinia, an antihost genome. Microbiol Mol Biol Rev 1998; 62: 1315-1352.
2 Heesemann J, Sing A, Trulzsch K. Yersinia’s stratagem: targeting innate and adaptive immune defense. Curr Opin Microbiol 2006; 9: 55-61.
3 Isberg RR, Hamburger Z, Dersch P. Signaling and invasin-promoted uptake via integrin receptors. Microbes Infect 2000; 2: 793-801.
4 Aepfelbacher M. Modulation of Rho GTPases by type III secretion system translocated effectors ofYersinia . Rev Physiol Biochem Pharmacol 2004; 152: 65-77.
5 Bliska JB. Yop effectors of Yersinia spp. and actin rearrangements. Trends Microbiol 2000; 8: 205-208.
6 Juris SJ, Shao F, Dixon JE. Yersinia effectors target mammalian signalling pathways. Cell Microbiol 2002; 4: 201-211.
7 Hoffmann C, Pop M, Leemhuis J. et al. TheYersinia pseudotuberculosis cytotoxic necrotizing factor (CNFY) selectively activates RhoA. J Biol Chem 2004; 279: 16026-16032.
8 Lockman HA, Gillespie RA, Baker BD. et al. Yersinia pseudotuberculosis produces a cytotoxic necrotizing factor. Infect Immun 2002; 70: 2708-2714.
9 Ruckdeschel K. Immunomodulation of macrophages by pathogenic Yersinia species. Arch Immunol Ther Exp (Warsz) 2002; 50: 131-137.
10 Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499-511.
11 Cornelis GR. The Yersinia Ysc-Yop ‘type III’ weaponry. Nat Rev Mol Cell Biol 2002; 3: 742-752.
12 Cornelis GR. The type III secretion injectisome. Nat Rev Microbiol 2006; 4: 811-825.
13 El Tahir Y, Skurnik M. YadA, the multifaceted Yersinia adhesin. Int J Med Microbiol 2001; 291: 209-218.
14 Heise T, Dersch P. Identification of a domain inYersinia virulence factor YadA that is crucial for extracellular matrix-specific cell adhesion and uptake. Proc Natl Acad Sci USA 2006; 103: 3375-3380.
15 Brugirard-Ricaud K, Duchaud E, Givaudan A. et al. Site-specific antiphagocytic function of the Photorhabdus luminescens type III secretion system during insect colonization. Cell Microbiol 2005; 7: 363-371.
16 Shao F, Merritt PM, Bao Z. et al. AYersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 2002; 109: 575-588.
17 Zhu M, Shao F, Innes RW. et al. The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site. Proc Natl Acad Sci USA 2004; 101: 302-307.
18 Sorg I, Hoffmann C, Dumbach J. et al. The C terminus ofYopT is crucial for activity and the N terminus is crucial for substrate binding. Infect Immun 2003; 71: 4623-4632.
19 Iriarte M, Cornelis GR. YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells. Mol Microbiol 1998; 29: 915-929.
20 Viboud GI, Mejia E, Bliska JB. Comparison of YopE and YopT activities in counteracting host signalling responses to Yersinia pseudotuberculosis infection. Cell Microbiol 2006; 8: 1504-1515.
21 Shao F, Vacratsis PO, Bao Z. et al. Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases. Proc Natl Acad Sci USA 2003; 100: 904-909.
22 Fueller F, Bergo MO, Young SG. et al. Endoproteolytic processing of RhoA by Rce1 is required for the cleavage of RhoA by Yersinia enterocolitica outer protein T. Infect Immun 2006; 74: 1712-1717.
23 Zumbihl R, Aepfelbacher M, Andor A. et al. The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA. J Biol Chem 1999; 274: 29289-29293.
24 Aepfelbacher M, Trasak C, Wilharm G. et al. Characterization ofYopT effects on Rho GTPases inYersinia enterocolitica-infected cells. J Biol Chem 2003; 278: 33217-33223.
25 Wong KW, Isberg RR. Yersinia pseudotuberculosis spatially controls activation and misregulation of host cell Rac1. PLoS Pathog 2005; 1: e16.
26 Grosdent N, Maridonneau-Parini I, Sory MP. et al. Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect Immun 2002; 70: 4165-4176.
27 Hoffmann R, vErp K, Trulzsch K. et al. Transcriptional responses of murine macrophages to infection with Yersinia enterocolitica . Cell Microbiol 2004; 6: 377-390.
28 Fritz G, Kaina B. Rho GTPases: promising cellular targets for novel anticancer drugs. Curr Cancer Drug Targets 2006; 6: 1-14.
29 Andor A, Trulzsch K, Essler M. et al. YopE of Yersinia, a GAP for Rho GTPases, selectively modulates Rac-dependent actin structures in endothelial cells. Cell Microbiol 2001; 3: 301-310.
30 Black D, Bliska J. The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxinYopE is required for antiphagocytic function and virulence. Mol Microbiol 2000; 37: 515-527.
31 Von Pawel-Rammingen U, Telepnev MV, Schmidt G. et al. GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure. Mol Microbiol 2000; 36: 737-748.
32 Scheffzek K, Ahmadian MR, Wittinghofer A. GTPase-activating proteins: helping hands to complement an active site. Trends Biochem Sci 1998; 23: 257-262.
33 Evdokimov AG, Tropea JE, Routzahn KM. et al. Crystal structure of theYersinia pestis GTPase activator YopE. Protein Sci 2002; 11: 401-408.
34 Krall R, Zhang Y, Barbieri JT. Intracellular membrane localization of pseudomonas ExoS and Yersinia YopE in mammalian cells. J Biol Chem 2004; 279: 2747-2753.
35 Ruckdeschel K, Pfaffinger G, Trulzsch K. et al. The proteasome pathway destabilizes Yersinia outer protein E and represses its antihost cell activities. J Immunol 2006; 176: 6093-6102.
36 Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 2003; 13: 13-22.
37 Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 2005; 21: 247-269.
38 Van Aelst L, D’Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev 1997; 11: 2295-2322.
39 Aili M, Isaksson EL, Hallberg B. et al. Functional analysis of the YopE GTPase-activating protein (GAP) activity of Yersinia pseudotuberculosis . Cell Microbiol 2006; 8: 1020-1033.
40 Michaelson D, Silletti J, Murphy G. et al. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J Cell Biol 2001; 152: 111-126.
41 Schotte P, Denecker G, Van Den Broeke A. et al. Targeting Rac1 by theYersinia effector proteinYopE inhibits caspase-1-mediated maturation and release of interleukin- 1beta. J Biol Chem 2004; 279: 25134-25142.
42 Viboud GI, Bliska JB. A bacterial type III secretion system inhibits actin polymerization to prevent pore formation in host cell membranes. Embo J 2001; 20: 5373-5382.
43 Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002; 82: 373-428.
44 Fällman M, Andersson K, Hakansson S. et al. Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774 cells. Infect Immun 1995; 63: 3117-3124.
45 Ruckdeschel K, Roggenkamp A, Schubert S. et al. Differential contribution of Yersinia enterocolitica virulence factors to evasion of microbicidal action of neutrophils. Infect Immun 1996; 64: 724-733.
46 Rosqvist R, Bolin I, Wolf-Watz H. Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving theYop2b protein. Infect Immun 1988; 56: 2139-2143.
47 Logsdon LK, Mecsas J. Requirement of theYersinia pseudotuberculosis effectors YopH and YopE in colonization and persistence in intestinal and lymph tissues. Infect Immun 2003; 71: 4595-4607.
48 Galyov EE, Hakansson S, Forsberg A. et al. A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. Nature 1993; 361: 730-732.
49 Hakansson S, Galyov EE, Rosqvist R. et al. TheYersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol Microbiol 1996; 20: 593-603.
50 Dukuzumuremyi JM, Rosqvist R, Hallberg B. et al. The Yersinia protein kinase A is a host factor inducible RhoA/Rac-binding virulence factor. J Biol Chem 2000; 275: 35281-35290.
51 Letzelter M, Sorg I, Mota LJ. et al. The discovery of SycO highlights a new function for type III secretion effector chaperones. Embo J 2006; 25: 3223-3233.
52 Trasak C, Zenner G, Vogel A. et al. Yersinia protein kinase YopO is activated by a novel G-actin binding process. J Biol Chem 2007; 282: 2268-2277.
53 Prehna G, Ivanov MI, Bliska JB. et al. Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors. Cell 2006; 126: 869-880.
54 Juris SJ, Rudolph AE, Huddler D. et al. A distinctive role for the Yersinia protein kinase: actin binding, kinase activation, and cytoskeleton disruption. Proc Natl Acad Sci USA 2000; 97: 9431-9436.
55 Wiley DJ, Nordfeldth R, Rosenzweig J. et al. The Ser/Thr kinase activity of the Yersinia protein kinase A (YpkA) is necessary for full virulence in the mouse, mollifying phagocytes, and disrupting the eukaryotic cytoskeleton. Microb Pathog 2006; 40: 234-243.
56 Juris J S, Shah K, Shokat K. et al. Identification of otubain 1 as a novel substrate for theYersinia protein kinase using chemical genetics and mass spectrometry. FEBS Lett 2006; 580: 179-183.
57 Soares L, Seroogy C, Skrenta H. et al. Two isoforms of otubain 1 regulate T cell anergy via GRAIL. Nat Immunol 2004; 5: 45-54.
58 Trulzsch K, Sporleder T, Igwe EI. et al. Contribution of the major secreted yops of Yersinia enterocolitica O:8 to pathogenicity in the mouse infection model. Infect Immun 2004; 72: 5227-5234.
59 Logsdon LK, Mecsas J. The proinflammatory response induced by wild-typeYersinia pseudotuberculosis infection inhibits survival of yop mutants in the gastrointestinal tract and Peyer’s patches. Infect Immun 2006; 74: 1516-1527.
60 Barnes PD, Bergman MA, Mecsas J. et al. Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine. J Exp Med 2006; 203: 1591-1601.
61 Black D, Bliska J. Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. Embo J 1997; 16: 2730-2744.
62 Persson C, Carballeira N, Wolf-Watz H. et al. The PTPaseYopH inhibits uptake ofYersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. Embo J 1997; 16: 2307-2318.
63 Black D, Montagna L, Zitsmann S. et al. Identification of an amino-terminal substrate-binding domain in theYersinia tyrosine phosphatase that is required for efficient recognition of focal adhesion targets. Mol Microbiol 1998; 29: 1263-1274.
64 Montagna LG, Ivanov MI, Bliska JB. Identification of residues in the N-terminal domain of the Yersinia tyrosine phosphatase that are critical for substrate recognition. J Biol Chem 2001; 276: 5005-5011.
65 Ivanov MI, Stuckey JA, Schubert HL. et al. Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence. Mol Microbiol 2005; 55: 1346-1356.
66 Yuan M, Deleuil F, Fallman M. Interaction between the Yersinia tyrosine phosphatase YopH and its macrophage substrate, Fyn-binding protein, Fyb. J Mol Microbiol Biotechnol 2005; 9: 214-223.
67 Hamid N, Gustavsson A, Andersson K. et al. YopH dephosphorylates Cas and Fyn-binding protein in macrophages. Microb Pathog 1999; 27: 231-242.
68 Brakebusch C, Fassler R. The integrin-actin connection, an eternal love affair. Embo J 2003; 22: 2324-2333.
69 Giancotti FG. Complexity and specificity of integrin signalling. Nat Cell Biol 2000; 2: E13-14.
70 Mogemark L, McGee K, Yuan M. et al. Disruption of target cell adhesion structures by the Yersinia effectorYopH requires interaction with the substrate domain of p130Cas. Eur J Cell Biol 2005; 84: 477-489.
71 Fisher ML, Castillo C, Mecsas J. Intranasal inoculation of mice with Yersinia pseudotuberculosis causes a lethal lung infection that is dependent on Yersinia outer proteins and PhoP. Infect Immun 2007; 75: 429-442.
72 Alonso A, Bottini N, Bruckner S, Rahmouni S. et al. Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH. J Biol Chem 2004; 279: 4922-4928.
73 Bruckner S, Rhamouni S, Tautz L. et al. Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells. J Biol Chem 2005; 280: 10388-10394.
74 Viboud GI, Bliska JB. Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 2005; 59: 69-89.
75 Gerke C, Falkow S, Chien YH. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. J Exp Med 2005; 201: 361-371.
76 Benabdillah R, Mota LJ, Lutzelschwab S. et al. Identification of a nuclear targeting signal in YopM from Yersinia spp. Microb Pathog 2004; 36: 247-261.
77 Skrzypek E, Cowan C, Straley SC. Targeting of the Yersinia pestis YopM protein into HeLa cells and intracellular trafficking to the nucleus. Mol Microbiol 1998; 30: 1051-1065.
78 McDonald C, Vacratsis PO, Bliska JB. et al. The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J Biol Chem 2003; 278: 18514-18523.
79 Sauvonnet N, Pradet-Balade B, Garcia-Sanz JA. et al. Regulation of mRNA expression in macrophages after Yersinia enterocolitica infection. Role of different Yop effectors. J Biol Chem 2002; 277: 25133-25142.
80 Heusipp G, Spekker K, Brast S. et al. YopM of Yersinia enterocolitica specifically interacts with alpha1-antitrypsin without affecting the anti-protease activity. Microbiology 2006; 152: 1327-1335.
81 Reisner BS, Straley SC. Yersinia pestis YopM: thrombin binding and overexpression. Infect Immun 1992; 60: 5242-5252.
82 Leung KY, Reisner BS, Straley SC. YopM inhibits platelet aggregation and is necessary for virulence of Yersinia pestis in mice. Infect Immun 1990; 58: 3262-3327.
83 Kerschen EJ, Cohen DA, Kaplan AM. et al. The plague virulence protein YopM targets the innate immune response by causing a global depletion of NK cells. Infect Immun 2004; 72: 4589-4602.
84 Boland A, Cornelis GR. Role of YopP in suppression of TNFα release by macrophages during Yersinia infection. Infect Immun 1998; 66: 1878-1884.
85 Palmer LE, Hobbie S, Galan JE. et al. YopJ of Y. pseudotuberculosis is required for the inhibition of macrophage TNFα production and downregulation of the MAP kinases p38 and JNK. Mol Microbiol 1998; 27: 953-965.
86 Schesser K, Spiik AK, Dukuzumuremyi JM. et al. The yopJ locus is required for Yersinia-mediated inhibition of NF-κB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol Microbiol 1998; 28: 1067-1079.
87 Orth K, Palmer LE, Bao ZQ. et al. Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science 1999; 285: 1920-1923.
88 Orth K, Xu Z, Mudgett MB. et al. Disruption of signaling byYersinia effectorYopJ, a ubiquitin-like protein protease. Science 2000; 290: 1594-1597.
89 Zhou H, Monack DM, Kayagaki N. et al. Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-?B activation. J Exp Med 2005; 202: 1327-1332.
90 Chen ZJ. Ubiquitin signalling in the NF-κB pathway. Nat Cell Biol 2005; 7: 758-765.
91 Mukherjee S, Keitany G, Li Y. et al. Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science 2006; 312: 1211-1214.
92 Mittal R, Peak-Chew SY, McMahon HT. Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling. Proc Natl Acad Sci USA 2006; 103: 18574-18579.
93 Haase R, Richter K, Pfaffinger G. et al. Yersinia outer protein P suppresses transforming growth factor- β-activated kinase-1 activity to impair innate immune signaling in Y. enterocolitica-infected cells. J Immunol 2005; 175: 8209-8217.
94 Thiefes A, Wolf A, Doerrie A. et al. TheY. enterocolitica effectorYopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway. EMBO Rep 2006; 7: 838-844.
95 Erfurth SE, Grobner S, Kramer U. et al. Y.enterocolitica induces apoptosis and inhibits surface molecule expression and cytokine production in murine dendritic cells. Infect Immun 2004; 72: 7045-7054.
96 Monack DM, Mecsas J, Bouley D. et al. Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice. J Exp Med 1998; 188: 2127-2137.
97 Trülzsch K, Sporleder T, Igwe EI. et al. Contribution of the major secreted yops of Y. enterocolitica O:8 to pathogenicity in the mouse infection model. Infect Immun 2004; 72: 5227-5234.
98 Ruckdeschel K, Mannel O, Richter K. et al. Yersinia outer protein P of Y. enterocolitica simultaneously blocks the NF-κB pathway and exploits lipopolysac-charide signaling to trigger apoptosis in macrophages. J Immunol 2001; 166: 1823-1831.
99 Zhang Y, Ting AT, Marcu KB. et al. Inhibition of MAPK and NF-κB pathways is necessary for rapid apoptosis in macrophages infected with Yersinia . J Immunol 2005; 74: 7939-7949.
100 Ruckdeschel K, Pfaffinger G, Haase R. et al. Signaling of apoptosis through TLRs critically involves toll/IL-1 receptor domain-containing adapter inducing IFNβ, but not MyD88, in bacteria-infected murine macrophages. J Immunol 2004; 173: 3320-3328.
101 Sing A, Rost D, Tvardovskaia N. et al. Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression. J Exp Med 2002; 196: 1017-1024.
102 Mueller CA, Broz P, Muller SA. et al. The V-antigen ofYersinia forms a distinct structure at the tip of injectisome needles. Science 2005; 310: 674-676.
103 Sing A, Reithmeier-Rost D, Granfors K. et al. A hypervariable N-terminal region of Yersinia LcrV determines Toll-like receptor 2-mediated IL-10 induction and mouse virulence. Proc Natl Acad Sci USA 2005; 102: 16049-16054.
104 Reithmeier-Rost D, Hill J, Elvin SJ. et al. The weak interaction of LcrV and TLR2 does not contribute to the virulence of Yersinia pestis . Microbes Infect 2007; 9: 997-1002.
105 Pouliot K, Pan N, Wang S. et al. Evaluation of the role of LcrV-Toll-like receptor 2-mediated immunomodulation in the virulence of Yersinia pestis . Infect Immun 2007; 75: 3571-3580.
106 Auerbuch V, Isberg RR. Growth of Yersinia pseudotuberculosis in mice occurs independently of Tolllike receptor 2 expression and induction of interleukin- 10. Infect Immun 2007; 75: 3561-3570.