Type III–delivered toxins that target signalling pathways

Luís J Mota; Guy R Cornelis

doi:10.1017/CBO9780511546280.007

6 - Type III–delivered toxins that target signalling pathways

Published online by Cambridge University Press: 15 September 2009

Luís J Mota and

Guy R Cornelis

Edited by

Alistair J. Lax

Show author details

Luís J Mota: Affiliation:
Division of Molecular Microbiology, Biozentrum, Universität Basel
Guy R Cornelis: Affiliation:
Division of Molecular Microbiology, Biozentrum, Universität Basel
Alistair J. Lax: Affiliation:
King's College London

Book contents

Get access

Summary

Upon infection, pathogenic bacteria must evade the immune defence of their host in order to multiply. To this end, many bacteria secrete toxins as part of their virulence mechanism. In a classical view, toxins are molecules that cause intoxication upon their release by bacteria into the body fluids. However, in the last 10 years a different class of bacterial toxin has been recognised. These molecules are not simply secreted by the bacterium, but instead they are delivered directly from the bacterial cytoplasm into the cytoplasm of the eukaryotic cell by specialised secretion machines present exclusively in Gram-negative bacteria. These are the so-called type III or type IV secretion systems, depending on whether they use a structure resembling the flagella or conjugative pili, respectively. In this chapter, we will describe the mode of action of toxins delivered by type III secretion systems (TTSSs). These molecules, currently known as type III effectors, have been shown to act on different host signalling pathways controlling a number of responses, and in some cases interfere with cell growth.

TYPE III SECRETION SYSTEMS

TTSSs are present not only in bacteria that are pathogenic for animals but also in bacteria pathogenic for plants or even in symbionts for plants and insects (Cornelis and Van Gijsegem, 2000). We will restrict our analysis to the action of type III effectors of animal pathogens. Among these, type III effectors have been identified in Yersinia spp., in Salmonella spp., in Shigella spp., in enteropathogenic and enterohaemorrhagic Escherichia coli, in Pseudomonas aeruginosa, and more recently, in Burkholderia pseudomallei (Stevens et al., 2003).

Type: Chapter
Information: Bacterial Protein Toxins
Role in the Interference with Cell Growth Regulation
, pp. 117 - 146

DOI: https://doi.org/10.1017/CBO9780511546280.007 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aepfelbacher, M, Trasak, C, Wilharm, G, Wiedemann, A, Trulzsch, K, Krauss, K, Gierschik, P, and Heesemann, J (2003). Characterization of YopT effects on Rho GTPases in Yersinia enterocolitica-infected cells. J. Biol. Chem., 278, 33217–33223CrossRef Google Scholar PubMed

Alonso, A, Bottini, N, Bruckner, S, Rahmouni, S, Williams, S, Schoenberger, S P, and Mustelin, T (2004). Lck dephosphorylation at Tyr394 and inhibition of T cell antigen receptor signalling by Yersinia phosphatase YopH. J. Biol. Chem. 279, 4922–4928CrossRef Google Scholar

Ador, A, Trulzsch, K, Essler, M, Roggenkamp, A, Wiedemann, A, Heesemann, J, and Aepfelbacher, M (2001). YopE of Yersinia, a GAP for Rho GTPases, selectively modulates Rac-dependent actin structures in endothelial cells. Cell Microbiol., 3, 301–310CrossRef Google Scholar

Barbieri, A M, Sha, Q, Bette-Bobillo, P, Stahl, P D, and Vidal, M (2001). ADP-ribosylation of Rab5 by ExoS of Pseudomonas aeruginosa affects endocytosis. Infect. Immun., 69, 5329–5234CrossRef Google Scholar PubMed

Black, D S and Bliska, J B (2000). The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence. Mol. Microbiol., 37, 515–527CrossRef Google Scholar PubMed

Black, D S, Marie-Cardine, A, Schraven, B, and Bliska, J B (2000). The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated signalling complex in macrophages. Cell. Microbiol., 2, 401–414CrossRef Google Scholar PubMed

Bliska, J B and Black, D S (1995). Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia pseudotuberculosis tyrosine phosphatase. Infect Immun., 63, 681–685Google Scholar PubMed

Boise, L H and Collins, C M (2001). Salmonella-induced cell death: Apoptosis, necrosis or programmed cell death?Trends. Microbiol., 9, 64–67CrossRef Google Scholar PubMed

Boland, A and Cornelis, G R (1998). Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection. Infect Immun., 66, 1878–1884Google Scholar PubMed

Boquet, P (2000). Small GTP binding proteins and bacterial virulence. Microbes Infect., 2, 837–843CrossRef Google Scholar PubMed

Bourdet-Sicard, R, Rudiger, M, Jockusch, B M, Gounon, P, Sansonetti, P J, and Nhieu, G T (1999). Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization. EMBO J., 18, 5853–5862CrossRef Google Scholar PubMed

Buttner, D and Bonas, U (2002). Port of entry – the type III secretion translocon. Trends Microbiol., 10, 186–192CrossRef Google Scholar PubMed

Caron, E and Hall, A (1998). Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science, 282, 1717–1721CrossRef Google Scholar PubMed

Chen, L M, Kaniga, K, and Galán, J E (1996a). Salmonella spp. are cytotoxic for cultured macrophages. Mol Microbiol., 21, 1101–1115CrossRef Google Scholar

Chen, Y, Smith, M R, Thirumalai, K, and Zychlinsky, A (1996b). A bacterial invasin induces macrophage apoptosis by binding directly to ICE. EMBO J., 15, 3853–60Google Scholar

Cornelis, G R (2002). Yersinia type III secretion: send in the effectors. J. Cell Biol., 158, 401–408CrossRef Google Scholar PubMed

Cornelis, G R and Gijsegem, F (2000). Assembly and function of type III secretory systems. Annu. Rev. Microbiol., 54, 735–774CrossRef Google Scholar PubMed

Crane, J K, Majumdar, S, and Pickhardt, D P (1999). Host cell death due to enteropathogenic Escherichia coli has features of apoptosis. Infect. Immun., 67, 2575–2584Google Scholar

Crane, J K, McNamara, B P, and Donnenberg, M S (2001). Role of EspF in host cell death induced by enteropathogenic Escherichia coli. Cell. Microbiol., 3, 197–211CrossRef Google Scholar PubMed

Dacheux, D, Goure, J, Chabert, J, Usson, Y, and Attree, I (2001). Pore-forming activity of type III system-secreted proteins leads to oncosis of Pseudomonas aeruginosa-infected macrophages. Mol. Microbiol., 40, 76–85CrossRef Google Scholar PubMed

Deleuil, F, Mogemark, L, Francis, M S, Wolf-Watz, H, and Fallman, M (2003). Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism. Cell. Microbiol., 5, 53–64CrossRef Google Scholar PubMed

Denecker, G, Declercq, W, Geuijen, C A, Boland, A, Benabdillah, R, Gurp, M, Sory, M P, Vandenabeele, P, and Cornelis, G R (2001). Yersinia enterocolitica YopP-induced apoptosis of macrophages involves the apoptotic signalling cascade upstream of Bid. J. Biol. Chem., 276, 19706–19714CrossRef Google Scholar

Denecker, G, Totemeyer, S, Mota, L J, Troisfontaines, P, Lambermont, I, Youta, C, Stainier, I, Ackermann, M, and Cornelis, G R (2002). Effect of low- and high-virulence Yersinia enterocolitica strains on the inflammatory response of human umbilical vein endothelial cells. Infect. Immun., 70, 3510–3520CrossRef Google Scholar PubMed

Dukuzumuremyi, J M, Rosqvist, R, Hallberg, B, Akerstrom, B, Wolf-Watz, H, and Schesser, K (2000). The Yersinia protein kinase A is a host factor inducible RhoA/Rac-binding virulence factor. J. Biol. Chem., 275, 35281–35290CrossRef Google Scholar PubMed

Elliot, S J, Krejany, E O, Mellies, J L, Robins-Browne, R M, Sasakawa, C, and Kaper, J B (2001). EspG, a novel type III system-secreted protein from enteropathogenic Escherichia coli with similarities to VirA of Shigella flexneri. Infect. Immun., 69, 4027–4033CrossRef Google Scholar

Feng, Y, Wente, S R, and Majerus, P W (2001). Overexpression of the inositol phosphatase SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export. Proc. Natl. Acad. Sci. USA, 98, 875–879CrossRef Google Scholar PubMed

Finck-Barbancon, V, Goranson, J, Zhu, L, Sawa, T, Wiener-Kronish, J P, Fleiszig, S M, Wu, C, Mende-Mueller, L, and Frank, D W (1997). ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol. Microbiol., 25, 547–557CrossRef Google Scholar PubMed

Frank, D W (1997). The exoenzyme S regulon of Pseudomonas aeruginosa. Mol. Microbiol., 26, 621–629CrossRef Google Scholar PubMed

Fraylick, J E, LaRocque, J R, Vincent, T S, and Olson, J C (2001). Independent and coordinate effects of ADP-ribosyltransferase and GTPase-activating activities of exoenzyme S on HT-29 epithelial cell function. Infect. Immun., 69, 5318–5328CrossRef Google Scholar PubMed

Fraylick, J E, Riese, M J, Vincent, T S, Barbieri, J T, and Olson, J C (2002). ADP-ribosylation and functional effects of Pseudomonas Exoenzyme S on cellular RalA. Biochem., 41, 9680–9687CrossRef Google Scholar PubMed

Frithz-Lindsten, E, Du, Y, Rosqvist, R, and Forsberg, A (1997). Intracellular targeting of exoenzyme S of Pseudomonas aeruginosa via type III-dependent translocation induces phagocytosis resistance, cytotoxicity and disruption of actin microfilaments. Mol. Microbiol., 25, 1125–1139CrossRef Google Scholar PubMed

Fu, Y and Galán, J E (1999). A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature, 401, 293–297CrossRef Google Scholar PubMed

Galán, J E (2001). Salmonella interactions with host cells: Type III secretion at work. Annu. Rev. Cell Dev. Biol., 17, 53–86CrossRef Google Scholar PubMed

Galyov, E E, Hakansson, S, Forsberg, A, and Wolf-Watz, H (1993). A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. Nature, 361, 730–732CrossRef Google Scholar PubMed

Ganesan, A K, Frank, D W, Misra, R P, Schmidt, G, and Barbieri, J T (1998). Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple sites. J. Biol. Chem., 273, 7332–7337CrossRef Google Scholar PubMed

Ganesan, A K, Vincent, T S, Olson, J C, and Barbieri, J T (1999). Pseudomonas aeruginosa exoenzyme S disrupts Ras-mediated signal transduction by inhibiting guanine nucleotide exchange factor-catalyzed nucleotide exchange. J. Biol. Chem., 274, 21823–21829CrossRef Google Scholar PubMed

Garrington, T P and Johnson, G L (1999). Organization and regulation of mitogen-activated protein kinase signalling pathways. Curr. Opin. Cell Biol., 11, 211–218CrossRef Google Scholar

Garrity-Ryan, L, Kazmierczak, B, Kowal, R, Comolli, J, Hauser, A, and Engel, J N (2000). The arginine finger domain of ExoT contributes to actin cytoskeleton disruption and inhibition of internalization of Pseudomonas aeruginosa by epithelial cells and macrophages. Infect. Immun., 68, 7100–7113CrossRef Google Scholar PubMed

Geiser, T K, Kazmierczak, B I, Garrity-Ryan, L K, Matthay, M A, and Engel, J N (2001). Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. Cell. Microbiol., 3, 223–236CrossRef Google Scholar PubMed

Goehring, U M, Schmidt, G, Pederson, K J, Aktories, K, and Barbieri, J T (1999). The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J. Biol. Chem., 274, 36369–36372CrossRef Google Scholar PubMed

Goosney, D L, Gruenheid, S, and Finlay, B B (2000). Gut feelings: Enteropathogenic E. coli (EPEC) interactions with the host. Annu. Rev. Cell Dev. Biol., 16, 173–189CrossRef Google Scholar

Grosdent, N, Maridonneau-Parini, I, Sory, M P, and Cornelis, G R (2002). Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect. Immun., 70, 4165–4176CrossRef Google Scholar PubMed

Hakansson, S, Galyov, E E, Rosqvist, R, and Wolf-Watz, H (1996). The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol. Microbiol., 20, 593–603CrossRef Google Scholar PubMed

Hall, A (1998). Rho GTPases and the actin cytoskeleton. Science, 279, 509–514CrossRef Google Scholar PubMed

Hamid, N, Gustavsson, A, Andersson, K, McGee, K, Persson, C, Rudd, C E, and Fallman, M (1999). YopH dephosphorylates Cas and Fyn-binding protein in macrophages. Microb. Pathogenesis, 27, 231–242CrossRef Google Scholar PubMed

Haraga, A and Miller, S I (2003). A Salmonella enterica serovar Typhimurium translocated leucine-rich repeat effector protein inhibits NF-κB-dependent gene expression. Infect. Immun., 71, 4052–4058CrossRef Google Scholar

Hardt, W D, Chen, L M, Schuebel, K E, Bustelo, X R, and Galán, J E (1998). S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell, 93, 815–826CrossRef Google Scholar PubMed

Hauser, A R and Engel, J N (1999). Pseudomonas aeruginosa induces type-III-secretion-mediated apoptosis of macrophages and epithelial cells. Infect. Immun., 67, 5530–5537Google Scholar PubMed

Hernandez, L D, Pypaert, M, Flavell, R A, and Galán, J E (2003). A Salmonella protein causes macrophage cell death by inducing autophagy. J. Cell. Biol., 163, 1123–1131CrossRef Google Scholar PubMed

Hersh, D, Monack, D M, Smith, M R, Ghori, N, Falkow, S, and Zychlinsky, A (1999). The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc. Natl. Acad. Sci. USA, 96, 2396–2401CrossRef Google Scholar PubMed

Hilbi, H, Moss, J E, Hersh, D, Chen, Y, Arondel, J, Banerjee, S, Flavell, R A, Yuan, J, Sansonetti, P J, and Zychlinsky, A (1998). Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB. J. Biol. Chem., 273, 32895–32900CrossRef Google Scholar PubMed

Iriarte, M and Cornelis, G R (1998). YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells. Mol. Microbiol., 29, 915–929CrossRef Google Scholar PubMed

Jesenberger, V, Procyk, K J, Yuan, J, Reipert, S, and Baccarini, M (2000). Salmonella-induced caspase-2 activation in macrophages: A novel mechanism in pathogen-mediated apoptosis. J. Exp. Med., 192, 1035–1046CrossRef Google Scholar PubMed

Journet, L, Agrain, C, Brosz, P, and Cornelis, G R (2003). The needle length of bacterial injectisomes is determined by a molecular ruler. Science, 302, 1757–1760CrossRef Google Scholar PubMed

Juris, S J, Rudolph, A E, Huddler, D, Orth, K, and Dixon, J E (2000). A distinctive role for the Yersinia protein kinase: Actin binding, kinase activation, and cytoskeleton disruption. Proc. Natl. Acad. Sci. USA, 97, 9431–9436CrossRef Google Scholar PubMed

Kaniga, K, Uralil, J, Bliska, J B, and Galán, J E (1996). A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium. Mol. Microbiol., 21, 633–641CrossRef Google Scholar PubMed

Karin, M and Lin, A (2002). NF-κB at the crossroads of life and death. Nat. Immunol., 3, 221–227CrossRef Google Scholar PubMed

Kaufman, M R, Jia, J, Zeng, L, Ha, U, Chow, M, and Jin, S (2000). Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS. Microbiology, 146, 2531–2541CrossRef Google Scholar PubMed

Kazmierczak, B I and Engel, J N (2002). Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA, Rac1, and Cdc42. Infect. Immun., 70, 2198–2205CrossRef Google Scholar PubMed

Kenny, B, Ellis, S, Leard, A D, Warawa, J, Mellor, H, and Jepson, M A (2002). Co-ordinate regulation of distinct host cell signalling pathways by multifunctional enteropathogenic Escherichia coli effector molecules. Mol. Microbiol., 44, 1095–1107CrossRef Google Scholar PubMed

Kenny, B and Jepson, M (2000). Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell. Microbiol., 2, 579–90CrossRef Google Scholar PubMed

Krall, R, Schmidt, G, Aktories, K, and Barbieri, J T (2000). Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein. Infect. Immun., 68, 6066–6068CrossRef Google Scholar PubMed

Krall, R, Sun, J, Pederson, K J, and Barbieri, J T (2002). In vivo Rho GTPase-activating protein activity of Pseudomonas aeruginosa cytotoxin ExoS. Infect. Immun., 70, 360–367CrossRef Google Scholar PubMed

Kubori, T and Galán, J (2003). Temporal regulation of Salmonella virulence factor function by proteasome-dependent protein degradation. Cell, 115, 333–342CrossRef Google Scholar

Lindgren, S W, Stojilkovic, I, and Heffron, F (1996). Macrophage killing is an essential virulence mechanism of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA, 93, 4197–4201CrossRef Google Scholar PubMed

Lyczak, J B, Cannon, C L, and Pier, G B (2000). Establishment of Pseudomonas aeruginosa infection: Lessons from a versatile opportunist. Microbes Infect., 2, 1051–1060CrossRef Google Scholar PubMed

Marcus, S L, Wenk, M R, Steele-Mortimer, O, and Finlay, B B (2001). A synaptojanin-homologous region of Salmonella typhimurium SigD is essential for inositol phosphatase activity and Akt activation. FEBS Lett., 494, 201–207CrossRef Google Scholar PubMed

McDonald, C, Vacratsis, P O, Bliska, J B, and Dixon, J E (2003). The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J. Biol. Chem., 278, 18514–18523CrossRef Google Scholar PubMed

McGuffie, E M, Frank, D W, Vincent, T S, and Olson, J C (1998). Modification of Ras in eukaryotic cells by Pseudomonas aeruginosa exoenzyme S. Infect. Immun., 66, 2607–2613Google Scholar PubMed

McNamara, B P, Koutsouris, A, O'Connell, C B, Nougayrede, J P, Donnenberg, M S, and Hecht, G (2001). Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function. J. Clin. Invest., 107, 621–629CrossRef Google Scholar PubMed

Menard, R, Prevost, M C, Gounon, P, Sansonetti, P, and Dehio, C (1996). The secreted Ipa complex of Shigella flexneri promotes entry into mammalian cells. Proc. Natl. Acad. Sci. USA, 93, 1254–1258CrossRef Google Scholar PubMed

Mills, S D, Boland, A, Sory, M P, Smissen, P, Kerbourch, C, Finlay, B B, and Cornelis, G R (1997). Yersinia enterocolitica induces apoptosis in macrophages by a process requiring functional type III secretion and translocation mechanisms and involving YopP, presumably acting as an effector protein. Proc. Natl. Acad. Sci. USA, 94, 12638–12643CrossRef Google Scholar PubMed

Monack, D M, Mecsas, J, Ghori, N, and Falkow, S (1997). Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc. Natl. Acad. Sci. USA, 94, 10385–10390CrossRef Google Scholar PubMed

Monack, D M, Raupach, B, Hromockyj, A E, and Falkow, S (1996). Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proc. Natl. Acad. Sci. USA, 94, 9833–9838CrossRef Google Scholar

Murli, S, Watson, R O, and Galán, J E (2001). Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells. Cell. Microbiol., 3, 795–810CrossRef Google Scholar PubMed

Niebuhr, K, Jouihri, N, Allaoui, A, Gounon, P, Sansonetti, P J, and Parsot, C (2000). IpgD, a protein secreted by the type III secretion machinery of Shigella flexneri, is chaperoned by IpgE and implicated in entry focus formation. Mol. Microbiol., 38, 8–19CrossRef Google Scholar PubMed

Niebuhr, K, Giuriato, S, Pedron, T, Philpott, D J, Gaits, F, Sable, J, Sheetz, M P, Parsot, C, Sansonetti, P J and Payrastre, B (2002). Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the Shigella flexneri effector IpgD reorganizes host cell morphology. EMBO J., 21, 5069–5078CrossRef Google Scholar PubMed

Norris, F A, Wilson, M P, Wallis, T S, Galyov, E E, and Majerus, P W (1998). SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc. Natl. Acad. Sci. USA, 95, 14057–14059CrossRef Google Scholar PubMed

Olson, J C, Fraylick, J E, McGuffie, E M, Dolan, K M, Yahr, T L, Frank, D W, and Vincent, T S (1999). Interruption of multiple cellular processes in HT-29 epithelial cells by Pseudomonas aeruginosa exoenzyme S. Infect. Immun., 67, 2847–54Google Scholar PubMed

Orth, K (2002). Function of the Yersinia effector YopJ. Curr. Opin. Microbiol., 5, 38–43CrossRef Google Scholar PubMed

Orth, K, Palmer, L E, Bao, Z Q, Stewart, S, Rudolph, A E, Bliska, J B, and Dixon, J E (1999). Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science, 285, 1920–1923CrossRef Google Scholar PubMed

Orth, K, Xu, Z, Mudgett, M B, Bao, Z Q, Palmer, L E, Bliska, J B, Mangel, W F, Staskawicz, B, and Dixon, J E (2000). Disruption of signalling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science, 290, 1594–1597CrossRef Google Scholar

Pederson, K J, Vallis, A J, Aktories, K, Frank, D W, and Barbieri, J T (1999). The amino-terminal domain of Pseudomonas aeruginosa ExoS disrupts actin filaments via small-molecular-weight GTP-binding proteins. Mol. Microbiol., 32, 393–401CrossRef Google Scholar PubMed

Persson, C, Nordfelth, R, Andersson, K, Forsberg, A, Wolf-Watz, H, and Fallman, M (1999). Localization of the Yersinia PTPase to focal complexes is an important virulence mechanism. Mol. Microbiol., 33, 828–838CrossRef Google Scholar PubMed

Phillips, R M, Six, D A, Dennis, E A, and Ghosh, P (2003). In vivo phospholipase activity of the Pseudomonas aeruginosa cytotoxin ExoU and protection of mammalian cells with phospholipase A2 inhibitors. J. Biol. Chem., 278, 41326–41332CrossRef Google Scholar PubMed

Riese, M J, Wittinghofer, A, and Barbieri, J T (2001). ADP ribosylation of Arg41 of Rap by ExoS inhibits the ability of Rap to interact with its guanine nucleotide exchange factor, C3G. Biochemistry, 40, 3289–94CrossRef Google Scholar PubMed

Rosqvist, R, Bolin, I, and Wolf-Watz, H (1988). Inhibition of phagocytosis in Yersinia pseudotuberculosis: A virulence plasmid-encoded ability involving the Yop2b protein. Infect. Immun., 56, 2139–2143Google Scholar PubMed

Rosqvist, R, Forsberg, A, and Wolf-Watz, H (1991). Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. Infect. Immun., 59, 4562–4569Google Scholar PubMed

Ruckdeschel, K, Mannel, O, Richter, K, Jacobi, C A, Trulzsch, K, Rouot, B, and Heesemann, J (2001). Yersinia outer protein P of Yersinia enterocolitica simultaneously blocks the nuclear factor-kappa B pathway and exploits lipopolysaccharide signalling to trigger apoptosis in macrophages. J. Immunol., 166, 1823–1831CrossRef Google Scholar

Ruiz-Albert, J, Yu, X J, Beuzon, C R, Blakey, A N, Galyov, E E, and Holden, D W (2002). Complementary activities of SseJ and SifA regulate dynamics of the Salmonella typhimurium vacuolar membrane. Mol. Microbiol., 44, 645–661CrossRef Google Scholar PubMed

Salcedo, S P and Holden, D W (2003). SseG, a virulence protein that targets Salmonella to the Golgi network. EMBO J., 22, 5003–5014CrossRef Google Scholar PubMed

Sansonetti, P J (2001). Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella, making sense of prokaryote-eukaryote cross-talks. FEMS Microbiol. Rev., 25, 3–14Google Scholar PubMed

Sato, H, Frank, D W, Hillard, C J, Feix, J B, Pankhaniya, R R, Moriyama, K, Finck-Barbancon, V, Buchaklian, A, Lei, M, Long, R M, Wiener-Kronish, J, and Sawa, T (2003). The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin, ExoU. EMBO J., 22, 2959–2969CrossRef Google Scholar PubMed

Sauvonnet, N, Lambermont, I, Bruggen, P, and Cornelis, G R (2002). YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway. Mol. Microbiol., 45, 805–815CrossRef Google Scholar PubMed

Schesser, K, Spiik, A K, Dukuzumuremyi, J M, Neurath, M F, Pettersson, S, and Wolf-Watz, H (1998). 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., 28, 1067–1079CrossRef Google Scholar PubMed

Shao, F, Merritt, P M, Bao, Z, Innes, R W, and Dixon, J E (2002). A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell, 109, 575–588CrossRef Google Scholar

Shao, F, Vacratsis, P O, Bao, Z, Bowers, K E, Fierke, C A, and Dixon, J E (2003). Biochemical chracterization of the Yersinia YopT protease: Cleavage site and recognition element in Rho GTPases. Proc. Natl. Acad. Sci. USA, 100, 904–909CrossRef Google Scholar

Skoudy, A, Nhieu, G T, Mantis, N, Arpin, M, Mounier, J, Gounon, P, and Sansonetti, P (1999). A functional role for ezrin during Shigella flexneri entry into epithelial cells. J. Cell Sci., 112, 2059–68Google Scholar PubMed

Steele-Mortimer, O, Knodler, L A, Marcus, S L, Scheid, M P, Goh, B, Pfeifer, C G, Duronio, V, and Finlay, B B (2000). Activation of Akt/protein kinase B in epithelial cells by the Salmonella typhimurium effector sigD. J. Biol. Chem., 275, 37718–37724CrossRef Google Scholar PubMed

Stender, S, Friebel, A, Linder, S, Rohde, M, Mirold, S, and Hardt, W D (2000). Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell. Mol. Microbiol., 36, 1206–1221CrossRef Google Scholar PubMed

Stevens, M P, Friebel, A, Taylor, L A, Wood, M W, Brown, P J, Hardt, W D, and Galyov, E E (2003). A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucelotide exchange factor activity. J. Bacteriol., 185, 4992–4996CrossRef Google Scholar

Sundin, C, Henriksson, M L, Hallberg, B, Forsberg, A, and Frithz-Lindsten, E (2001). Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering with Ras signal transduction. Cell. Microbiol., 3, 237–246CrossRef Google Scholar

Takai, Y, Sasaki, T, and Matosaki, T (2001). Small GTP-binding proteins. Physiol. Rev., 81, 153–208CrossRef Google Scholar PubMed

Terebiznik, M R, Vieira, O V, Marcus, S L, Slade, A, Yip, C M, Trimble, W S, Meyer, T, Finlay, B B, and Grinstein, S (2002). Elimination of host cell PtdIns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella. Nat. Cell. Biol., 4, 766–773CrossRef Google Scholar PubMed

Tran Van Nhieu, G, Bourdet-Sicard, R, Dumenil, G, Blocker, A, and Sansonetti, P J (2000). Bacterial signals and cell responses during Shigella entry into epithelial cells. Cell. Microbiol., 2, 187–193CrossRef Google Scholar PubMed

Nhieu, G T, Caron, E, Hall, A, and Sansonetti, P J (1999). IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J., 18, 3249–3262CrossRef Google Scholar

Uchiya, K, Tobe, T, Komatsu, K, Suzuki, T, Watarai, M, Fukuda, I, Yoshikawa, M, and Sasakawa, C (1995). Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading. Mol. Microbiol., 17, 241–250CrossRef Google Scholar PubMed

Vallis, A J, Finck-Barbancon, V, Yahr, T L, and Frank, D W (1999). Biological effects of Pseudomonas aeruginosa type III-secreted proteins on CHO cells. Infect. Immun., 67, 2040–2044Google Scholar PubMed

Velden, A W, Lindgren, S W, Worley, M J, and Heffron, F (2000). Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype Typhimurium. Infect. Immun., 68, 5702–5709CrossRef Google Scholar PubMed

Vanhaesebroeck, B and Alessi, D R (2000). The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J., 346, 561–576Google Scholar PubMed

Viboud, G I, So, S S K, Ryndak, M B, and Bliska, J B (2003). Proinflammatory signalling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with Yersinia pseudotuberculosis. Mol. Microbiol., 47, 1305–1315CrossRef Google Scholar PubMed

Vincent, T S, Fraylick, J E, McGuffie, E M, and Olson, J C (1999). ADP-ribosylation of oncogenic Ras proteins by Pseudomonas aeruginosa exoenzyme S in vivo. Mol. Microbiol., 32, 1054–1064CrossRef Google Scholar PubMed

Visser, L G, Annema, A, and vanFurth, R (1995). Role of Yops in inhibition of phagocytosis and killing of opsonized Yersinia enterocolitica by human granulocytes. Infect. Immun., 63, 2570–2575Google Scholar PubMed

Pawel-Rammingen, U, Telepnev, M V, Schmidt, G, Aktories, K, Wolf-Watz, H, and Rosqvist, R (2000). GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: A mechanism for disruption of actin microfilament structure. Mol. Microbiol., 36, 737–748CrossRef Google Scholar

Yao, T, Mecsas, J, Healy, J I, Falkow, S, and Chien, Y (1999). Suppression of T and B lymphocyte activation by a Yersinia pseudotuberculosis virulence factor, YopH. J. Exp. Med., 190, 1343–50CrossRef Google Scholar

Waterman, S R and Holden, D W (2003). Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell. Microbiol., 5, 510–511CrossRef Google Scholar PubMed

Yoshida, S, Katayama, E, Kuwae, A, Mimuro, H, Suzuki, T, and Sasakawa, C (2002). Shigella deliver an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization. EMBO J., 21, 2923–2935CrossRef Google Scholar PubMed

Zhou, D, Chen, L M, Hernandez, L, Shears, S B, and Gálan, J E (2001). A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol., 39, 248–259CrossRef Google Scholar PubMed

Zumbihl, R, Aepfelbacher, M, Andor, A, Jacobi, C A, Ruckdeschel, K, Rouot, B, and Heesemann, J (1999). The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA. J. Biol. Chem. 274, 29289–29293CrossRef Google Scholar

Zychlinsky, A, Kenny, B, Menard, R, Prevost, M C, Holland, I B, and Sansonetti, P J (1994). IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol. Microbiol., 11, 619–627CrossRef Google Scholar PubMed

Zychlinsky, A, Prevost, M C, and Sansonetti, P J (1992). Shigella flexneri induces apoptosis in infected macrophages. Nature, 358, 167–169CrossRef Google Scholar PubMed

Zychlinsky, A, Thirumalai, K, Arondel, J, Cantey, J R, Aliprantis, A O, and Sansonetti, P J (1996). In vivo apoptosis in Shigella flexneri infections. Infect. Immun. 64, 5357–5365Google Scholar PubMed

Book contents

6 - Type III–delivered toxins that target signalling pathways

Summary

Access options

References

Save book to Kindle

Save book to Dropbox

Save book to Google Drive