Escherichia coli Subtilase Cytotoxin
Abstract
:1. Introduction
2. Basic Biological Characterisation
3. Intracellular Target and Cytotoxic Mechanism
4. Intracellular Trafficking
5. Receptor Specificity
6. Strain Distribution of SubAB
7. Pathological Features and Potential Role in Human Disease
8. Applications of SubAB as a Cell Biological Tool and as a Therapeutic Agent
9. Conclusions
Acknowledgements
References
- Fan, E.; Merritt, E.A.; Verlinde, C.L.M.J.; Hol, W.G.J. AB(5) toxins: Structures and inhibitor design. Curr. Opin. Struct. Biol. 2000, 10, 680–686. [Google Scholar] [PubMed]
- Paton, A.W.; Srimanote, P.; Talbot, U.M.; Wang, H.; Paton, J.C. A new family of potent AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. J. Exp. Med. 2004, 200, 35–46. [Google Scholar] [PubMed]
- Paton, A.W.; Woodrow, M.C.; Doyle, R.M.; Lanser, J.A.; Paton, J.C. Molecular characterization of a Shiga-toxigenic Escherichia coli O113:H21 strain lacking eae responsible for a cluster of cases of hemolytic-uremic syndrome. J. Clin. Microbiol. 1999, 37, 3357–3361. [Google Scholar] [PubMed]
- Paton, J.C.; Paton, A.W. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 1998, 11, 450–479. [Google Scholar] [PubMed]
- Karmali, M.A.; Petric, M.; Lim, C.; Fleming, P.C.; Arbus, G.S.; Lior, H. The asociation between idiopathic hemolytic uremic syndrome and infection by Verotoxin-producing Escherichia coli. J. Infect. Dis. 1985, 151, 775–782. [Google Scholar] [PubMed]
- Siezen, R.J.; Leunissen, J.A.M. Subtilases: The superfamily of subtilisin-like serine proteases. Protein Sci. 1997, 6, 501–523. [Google Scholar] [PubMed]
- Noda, M.; Yutsudo, T.; Nakabayashi, N.; Hirayama, T.; Takeda, Y. Purification and some properties of Shiga-like toxin from Escherichia coli O157:H7 that is immunologically identical to Shiga toxin. Microb. Pathog. 1987, 2, 339–349. [Google Scholar] [PubMed]
- Yutsudo, T.; Nakabayashi, N.; Hirayama, T.; Takeda, Y. Purification and some properties of a Vero toxin from Escherichia coli O157:H7 that is immunologically unrelated to Shiga toxin. Microb. Pathog. 1987, 3, 21–30. [Google Scholar] [PubMed]
- Richardson, S.E.; Rotman, T.A.; Jay, V.; Smith, C.R.; Becker, L.E.; Petric, M.; Olivieri, N.F.; Karmali, M.A. Experimental verocytotoxemia in rabbits. Infect. Immun. 1992, 60, 4154–4167. [Google Scholar] [PubMed]
- Lindgren, S.W.; Samuel, J.E.; Schmitt, C.K.; O'Brien, A.D. The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related toxins of enterohemorrhagic Escherichia coli differ when measured by Vero cell cytotoxicity but not by mouse lethality. Infect. Immun. 1994, 62, 623–631. [Google Scholar] [PubMed]
- Fujii, J.; Matsui, T.; Heatherly, D.P.; Schlegel, K.H.; Lobo, P.I.; Yutsudo, T.; Ciraolo, G.M.; Morris, R.E.; Obrig, T. Rapid apoptosis induced by Shiga toxin in HeLa cells. Infect. Immun. 2003, 71, 2724–2735. [Google Scholar] [PubMed]
- Morinaga, N.; Yahiro, K.; Matsuura, G.; Watanabe, M.; Nomura, F.; Moss, J.; Noda, M. Two distinct cytotoxic activities of subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli. Infect. Immun. 2007, 75, 488–496. [Google Scholar] [PubMed]
- Lass, A.; Kujawa, M.; McConnell, E.; Paton, A.W.; Paton, J.C.; Wójcik, C. Decreased ER-associated degradation of α-TCR induced by Grp78 depletion with the SubAB cytotoxin. Int. J. Biochem. Cell Biol. 2008, 40, 2865–2879. [Google Scholar] [PubMed]
- Paton, A.W.; Beddoe, T.; Thorpe, C.M.; Whisstock, J.C.; Wilce, M.C.J.; Rossjohn, J.; Talbot, U.M.; Paton, J.C. AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 2006, 443, 548–552. [Google Scholar] [PubMed]
- Gething, M.J. Role and regulation of the ER charperone BiP. Cell Devel. Biol. 1999, 10, 465–472. [Google Scholar] [CrossRef]
- Hendershot, L.M. The ER chaperone BiP is a master regulator of ER function. Mt. Sinai J. Med. 2004, 71, 289–297. [Google Scholar] [PubMed]
- Boyce, M.; Yuan, J. Cellular response to endoplasmic reticulum stress: A matter of life or death. Cell Death Differ. 2006, 13, 363–373. [Google Scholar] [PubMed]
- Szegezdi, E.; Logue, S.E.; Gorman, A.M.; Samali, A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Reports 2006, 7, 880–885. [Google Scholar] [CrossRef] [PubMed]
- Wolfson, J.; Thorpe, C.M.; May, K.L.; Paton, J.C.; Jandhyala, D.M.; Paton, A.W. Subtilase cytotoxin activates PERK, ATF6 and IRE1 endoplasmic reticulum stress-signaling pathways. Cell. Microbiol. 2008, 10, 795–806. [Google Scholar] [PubMed]
- Shen, J.; Snapp, E.L.; Lippincott-Schwartz, J.; Prywes, R. Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response. Mol. Cell. Biol. 2005, 25, 921–932. [Google Scholar] [PubMed]
- Wang, H.; Paton, J.C.; Paton, A.W. Pathologic changes in mice induced by subtilase cytotoxin, a potent new Escherichia coli AB5 toxin that targets the endoplasmic reticulum. J. Infect. Dis. 2007, 196, 1093–1101. [Google Scholar] [PubMed]
- Morinaga, N.; Yahiro, K.; Matsuura, G.; Moss, J.; Noda, M. Subtilase cytotoxin, produced by Shiga-toxigenic Escherichia coli, transiently inhibits protein synthesis of Vero cells via degradation of BiP and induces cell cycle arrest at G1 by downregulation of cyclin D1. Cell. Microbiol. 2008, 10, 921–929. [Google Scholar] [CrossRef] [PubMed]
- Matsuura, G.; Morinaga, N.; Yahiro, K.; Komine, R.; Moss, J.; Yoshida, H.; Noda, M. Novel subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli induces apoptosis in vero cells via mitochondrial membrane damage. Infect. Immun. 2009, 77, 2919–2924. [Google Scholar] [PubMed]
- Chong, D.C.; Paton, J.C.; Thorpe, C.M.; Paton, A.W. Clathrin-dependent trafficking of subtilase cytotoxin, a novel AB5 toxin that targets the endoplasmic reticulum chaperone BiP. Cell. Microbiol. 2008, 10, 795–806. [Google Scholar] [CrossRef] [PubMed]
- Smith, R.D.; Willett, R.; Kudlyk, T.; Pokrovskaya, I.; Paton, A.W.; Paton, J.C.; Lupashin, V.V. The COG comples, Rab6 and COPI define a novel Golgi retrograde trafficking pathway that is exploited by SubAB toxin. Traffic 2009, 10, 1502–1517. [Google Scholar] [CrossRef] [PubMed]
- Lencer, W.I.; Tsai, B. The intracellular voyage of cholera toxin: Going retro. Trends Biochem. Sci. 2003, 28, 639–645. [Google Scholar] [PubMed]
- Yu, M.; Haslam, D.B. Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/ERdj3. Infect. Immun. 2005, 73, 2524–2532. [Google Scholar] [PubMed]
- Stein, P.E.; Boodhoo, A.; Armstrong, G.D.; Heerze, L.D.; Cockle, S.A.; Klein, M.H.; Read, R.J. Structure of a pertussis toxin-sugar complex as a model for receptor binding. Nature Struct. Biol. 1994, 1, 591–596. [Google Scholar]
- Yahiro, K.; Morinaga, N.; Satoh, M.; Matsuura, G.; Tomonaga, T.; Nomura, F.; Moss, J.; Noda, M. Identification and characterization of receptors for vacuolating activity of subtilase cytotoxin. Mol. Microbiol. 2006, 62, 480–490. [Google Scholar] [PubMed]
- Kondo, Y.; Tokuda, N.; Fan, X.; Yamashita, T.; Honke, K.; Takematsu, H.; Togayachi, A.; Ohta, M.; Kotzusumi, Y.; Narimatsu, H.; Tajima, O.; Furukawa, K.; Furukawa, K. Glycosphingolipids are not pivotal receptors for Subtilase cytotoxin in vivo: Sensitivity analysis with glycosylation-defective mutant mice. Biochem. Biophys. Res. Commun. 2009, 378, 179–181. [Google Scholar] [CrossRef] [PubMed]
- Byres, E.; Paton, A.W.; Paton, J.C.; Löfling, J.C.; Smith, D.F.; Wilce, M.C.J.; Talbot, U.M.; Chong, D.C.; Yu, H.; Huang, S.; Chen, X.; Varki, N.M.; Varki, A.; Rossjohn, J.; Beddoe, T. Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 2008, 456, 648–652. [Google Scholar] [PubMed]
- Merritt, E.A.; Sarfarty, S.; Jobling, M.G.; Chang, T.; Holmes, R.K.; Hirst, T.R.; Hol, W.G. Structural studies of receptor binding by cholera toxin mutants. Protein Sci. 1997, 6, 1516–1528. [Google Scholar] [PubMed]
- Merritt, E.A.; Sixma, T.K.; Kalk, K.H.; van Zanten, B.A.; Hol, W.G. Galactose-binding site in Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT). Mol. Microbiol. 1994, 13, 745–753. [Google Scholar] [CrossRef] [PubMed]
- Ling, H.; Bast, D.; Brunton, J.L.; Read, R.J. Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry 1998, 37, 1777–1788. [Google Scholar] [PubMed]
- Paton, A.W.; Paton, J.C. Multiplex PCR for direct detection of Shiga toxigenic Escherichia coli producing the novel subtilase cytotoxin. J. Clin. Microbiol. 2005, 43, 2944–2947. [Google Scholar] [PubMed]
- Izumiya, H.; Iyoda, S.; Terajima, J.; Ohnishi, M.; Yamasaki, S.; Watanabe, H. Distribution of the subA gene among LEE-negative STEC isolates in Japan. In Abstracts of the Sixth International Symposium on Shiga toxin (Verocytotoxin) -Producing Escherichia coli Infections (VTEC2006), Sixth International Symposium on Shiga toxin (Verocytotoxin) -Producing Escherichia coli Infections (VTEC2006), Melbourne, Australia; 2006; Abstract P07.2.11, pp. 84–85. [Google Scholar]
- Khaitan, A.; Jandhyala, D.M.; Thorpe, C.M.; Ritchie, J.M.; Paton, A.W. The operon encoding SubAB a novel cytotoxin is present in Shiga toxin-producing Escherichia coli isolates from the United States. J. Clin. Microbiol. 2007, 45, 1374–1375. [Google Scholar] [PubMed]
- Cergole-Novella, M.C.; Nishimura, L.S.; dos Santos, L.F.; Irino, K.; Vaz, T.M.I.; Bergamini, A.M.M.; Guth, B.E.C. Distribution of virulence profiles related to new toxins and putative adhesins in Shiga toxin-producing Escherichia coli isolated from diverse sources in Brazil. FEMS Microbiol. Lett. 2008, 274, 329–334. [Google Scholar]
- Wolfson, J.J.; Jandhyala, D.M.; Gorczyca, L.A.; Qadeer, Z.; Manning, S.D.; Hadler, J.; Rudrik, J.T.; Thorpe, C.M. Prevalence of the operon encoding subtilase cytotoxin in non-O157 Shiga toxin-producing Escherichia coli isolated from humans in the United States. J. Clin. Microbiol. 2009, 47, 3058–3059. [Google Scholar] [PubMed]
- Slanec, T.; Fruth, A.; Creuzburg, K.; Schmidt, H. Molecular analysis of virulence profiles and Shiga toxin genes in food-borne Shiga toxin-producing Escherichia coli. Appl. Environ. Microbiol. 2009, 75, 6187–6197. [Google Scholar] [PubMed]
- Karama, M.; Johnson, R.P.; Holtslander, R.; McEwen, S.A.; Gyles, C.L. Prevalence and characterization of verotoxin-producing Escherichia coli (VTEC) in cattle from an Ontario abattoir. Can. J. Vet. Res. 2008, 72, 297–302. [Google Scholar] [PubMed]
- Irino, K.; Vieira, M.A.M.; Gomes, T.A.T.; Naves, Z.V.F.; Guth, B.E.C.; Oliveira, M.G.; Timm, C.D.; Pigatto, C.P.; Farah, S.M.S.S.; Vaz, T.M.I. The subAB operon encoding the subtilase cytotoxin (SubAB) is present only among Shiga toxin-producing Escherichia coli. In Abstracts of the Seventh International Symposium on Shiga toxin (Verocytotoxin)-Producing Escherichia coli Infections (VTEC2009), Seventh International Symposium on Shiga toxin (Verocytotoxin)-Producing Escherichia coli Infections (VTEC2009), Buenos Aires, Argentina; 10-13 May 2009; Abstract P02.4.7, p. 95. [Google Scholar]
- Gerhardt, E.; Miliwebsky, E.; Rivas, M.; Ibarra, C. Detection of subtilase cytotoxin (SubAB) in Shiga toxin-producing Escherichia colistrains associated with hemolytic uremic syndrome in Argentine children. In Abstracts of the Seventh International Symposium on Shiga toxin (Verocytotoxin)-Producing Escherichia coli Infections (VTEC2009), Seventh International Symposium on Shiga toxin (Verocytotoxin)-Producing Escherichia coli Infections (VTEC2009), Buenos Aires, Argentina; 10-13 May 2009; Abstract P04.4.3, p. 101. [Google Scholar]
- Tozzoli, R.; Caprioli, A.; Cappannella, S.; Michelacci, V.; Marziano, M.L.; Morabito, S. Production of the subtilase AB5 cytotoxin by Shiga toxin-negative Escherichia coli. J. Clin. Microbiol. 2010, 48, 178–183. [Google Scholar] [PubMed]
- Srimanote, P.; Paton, A.W.; Paton, J.C. Characterization of a novel type IV pilus locus carried on the large plasmid of human-virulent strains of locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli. Infect. Immun. 2002, 70, 3094–3100. [Google Scholar] [CrossRef] [PubMed]
- Talbot, U.M.; Paton, J.C.; Paton, A.W. Protective immunization of mice with an active site mutant of subtilase cytotoxin of Shiga toxigenic Escherichia coli. Infect. Immun. 2005, 73, 4432–4436. [Google Scholar] [CrossRef] [PubMed]
- Hu, C.A.; Dougan, S.K.; Winter, S.V.; Paton, A.W.; Paton, J.C.; Ploegh, H.L. Subtilase cytotoxin cleaves newly synthesised BiP and blocks antibody secretion in B lymphocytes. J. Exp. Med. 2009, 206, 2429–2440. [Google Scholar] [PubMed]
- Yamazaki, H.; Hiramatsu, N.; Hayakawa, K.; Okamura, M.; Huang, T.; Nakajima, S.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Activation of the Akt-NF-κB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J. Immunol. 2009, 183, 1480–1487. [Google Scholar] [PubMed]
- Harama, D.; Koyama, K.; Mukai, M.; Shimokawa, N.; Miyata, M.; Nakamura, Y.; Ohnuma, Y.; Ogawa, H.; Matsuoka, S.; Paton, A.W.; Paton, J.C.; Kitamura, M.; Nakao, A. A sub-cytotoxic dose of subtilase cytotoxin prevents LPS-induced inflammatory responses, depending on its capacity to induce the unfolded protein response. J. Immunol. 2009, 183, 1368–1374. [Google Scholar] [PubMed]
- Varki, A. Loss of N-glycolylneuraminic acid in humans: Mechanisms, consequences, and implications for hominid evolution. Am. J. Phys. Anthropol. 2001, Suppl.33, 54–69. [Google Scholar]
- Tangvoranuntakul, P.; Gagneux, P.; Diaz, S.; Bardor, M.; Varki, N.; Varki, A.; Muchmore, E. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc. Natl. Acad. Sci. USA 2003, 100, 12045–12050. [Google Scholar]
- Takano, Y.; Hiramatsu, N.; Okamura, M.; Hayakawa, K.; Shimada, T.; Kasai, A.; Yokouchi, M.; Shitamura, A.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Suppression of cytokine responses by GATA inhibitor K-7174: Implication for unfolded protein response. Biochem. Biophys. Res. Comm. 2007, 360, 470–475. [Google Scholar]
- Hayakawa, K.; Hiramatsu, N.; Okamura, M.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Blunted activation of NF-κB and NF-κB-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response. Biochem. Biophys. Res. Comm. 2008, 365, 47–53. [Google Scholar]
- Hayakawa, K.; Hiramatsu, N.; Okamura, M.; Yamazaki, H.; Nakajima, S.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Acquisition of anergy to proinflammatory cytokines in nonimmune cells through endoplasmic reticulum stress response: A mechanism for subsidence of inflammation. J. Immunol. 2009, 182, 1182–1191. [Google Scholar] [PubMed]
- Du, S.; Hiramatsu, N.; Hayakawa, K.; Kasai, A.; Okamura, M.; Huang, T.; Yao, J.; Takeda, M.; Araki, I.; Sawada, N.; Paton, A.W.; Paton, J.C.; Kitamura, M. Suppression of NF-κB by cyclosporin A and tacrolimus (FK506) via induction of the C/EBP family: Implication for unfolded protein response. J. Immunol. 2009, 182, 7201–7211. [Google Scholar] [PubMed]
- Okamura, M.; Takano, Y.; Hiramatsu, N.; Hayakawa, K.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Suppression of cytokine responses by indomethacin in podocytes: A mechanism through induction of unfolded protein response. Am. J. Physiol. Renal Physiol. 2009, 295, F1495–F1503. [Google Scholar]
- Huang, T.; Wan, Y.; Zhu, Y.; Fang, X.; Hiramatsu, N.; Hayakawa, K.; Paton, A.W.; Paton, J.C.; Kitamura, M.; Yao, J. Downregulation of gap junction expression and function by endoplasmic reticulum stress. J. Cell Biochem. 2009, 107, 973–983. [Google Scholar] [PubMed]
- Buchkovich, N.J.; Maguire, T.G.; Yu, Y.; Paton, A.W.; Paton, J.C.; Alwine, J.C. Human Cytomegalovirus specifically controls the levels of the endoplasmic reticulum chaperone BiP/GRP78, which is required for virion assembly. J. Virol. 2008, 82, 31–39. [Google Scholar] [PubMed]
- Buchkovich, N.J.; Maguire, T.G.; Paton, A.W.; Paton, J.C.; Alwine, J.C. The endoplasmic reticulum chaperone BiP/GRP78 is important in the structure and function of the HCMV assembly compartment. J. Virol. 2009, 83, 11421–11428. [Google Scholar] [PubMed]
- Wati, S.; Soo, M.L.; Zilm, P.; Li, P.; Paton, A.W.; Burrell, C.J.; Beard, M.; Carr, J.M. Dengue virus infection induces GRP78 which acts to chaperone viral antigen production. J. Virol. 2009, 83, 12871–12880. [Google Scholar] [PubMed]
- Macario, A.J.L.; Conway de Macario, E. Sick chaperones, cellular stress and disease. N. Engl. J. Med. 2005, 353, 1489–1501. [Google Scholar] [PubMed]
- Li, J.; Lee, A.S. Stress induction of GRP78/BiP and its role in cancer. Curr. Mol. Med. 2006, 6, 45–54. [Google Scholar] [PubMed]
- Backer, J.M.; Krivoshein, A.; Hamby, C.V.; Pizzonia, J.; Gilbert, K.; Ray, Y.S.; Brand, H.; Paton, A.W.; Paton, J.C.; Backer, M.V. Chaperone-targeting cytotoxin and ER stress-inducing drug synergize to kill cancer cells. Neoplasia 2009, 11, 1165–1173. [Google Scholar] [PubMed]
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Paton, A.W.; Paton, J.C. Escherichia coli Subtilase Cytotoxin. Toxins 2010, 2, 215-228. https://doi.org/10.3390/toxins2020215
Paton AW, Paton JC. Escherichia coli Subtilase Cytotoxin. Toxins. 2010; 2(2):215-228. https://doi.org/10.3390/toxins2020215
Chicago/Turabian StylePaton, Adrienne W., and James C. Paton. 2010. "Escherichia coli Subtilase Cytotoxin" Toxins 2, no. 2: 215-228. https://doi.org/10.3390/toxins2020215