Acknowledgement
This work was supported by the KRIBB Research Initiative Program (KGS1352221, KGM5322214) and a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2018M3A9H3023077, 2021M3A9H3016046) and and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) (2022R1A2C1003699) and also the "Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ015001022022)" Rural Development Administration, Republic of Korea.
References
- Lee MS, Tesh VL. 2019. Roles of shiga toxins in immunopathology. Toxins (Basel) 11: 212.
- Park JY, Jeong YJ, Park SK, Yoon SJ, Choi S, Jeong DG, et al. 2017. Shiga toxins induce apoptosis and ER stress in human retinal pigment epithelial cells. Toxins (Basel) 9: 319.
- Lee KS, Lee J, Lee P, Kim CU, Kim DJ, Jeong YJ, et al. 2020. Exosomes released from Shiga toxin 2a-treated human macrophages modulate inflammatory responses and induce cell death in toxin receptor expressing human cells. Cell. Microbiol. 22: e13249.
- Heredia N, Garcia S. 2018. Animals as sources of food-borne pathogens: A review. Anim. Nutr. 4: 250-255. https://doi.org/10.1016/j.aninu.2018.04.006
- Griffin PM, Tauxe RV. 1991. The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol. Rev. 13: 60-98. https://doi.org/10.1093/oxfordjournals.epirev.a036079
- Majowicz SE, Scallan E, Jones-Bitton A, Sargeant JM, Stapleton J, Angulo FJ, et al. 2014. Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis. Foodborne Pathog. Dis. 11: 447-455. https://doi.org/10.1089/fpd.2013.1704
- Tarr PI, Gordon CA, Chandler WL. 2005. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365: 1073-1086. https://doi.org/10.1016/S0140-6736(05)74232-X
- Kaper JB, Nataro JP, Mobley HL. 2004. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2: 123-140. https://doi.org/10.1038/nrmicro818
- Havelaar AH, Kirk MD, Torgerson PR, Gibb HJ, Hald T, Lake RJ, et al. 2015. World health organization global estimates and regional comparisons of the burden of foodborne disease in 2010. PLoS Med. 12: e1001923.
- Fukushima H, Hashizume T, Morita Y, Tanaka J, Azuma K, Mizumoto Y, et al. 1999. Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr. Int. 41: 213-217. https://doi.org/10.1046/j.1442-200X.1999.4121041.x
- Bielaszewska M, Middendorf B, Kock R, Friedrich AW, Fruth A, Karch H, et al. 2008. Shiga toxin-negative attaching and effacing Escherichia coli: distinct clinical associations with bacterial phylogeny and virulence traits and inferred in-host pathogen evolution. Clin. Infect. Dis. 47: 208-217. https://doi.org/10.1086/589245
- Pires SM, Majowicz S, Gill A, Devleesschauwer B. 2019. Global and regional source attribution of Shiga toxin-producing Escherichia coli infections using analysis of outbreak surveillance data. Epidemiol. Infect. 147: e236.
- Erickson MC, Doyle MP. 2007. Food as a vehicle for transmission of Shiga toxin-producing Escherichia coli. J. Food Prot. 70: 2426-2449. https://doi.org/10.4315/0362-028X-70.10.2426
- Persad AK, LeJeune JT. 2014. Animal reservoirs of Shiga toxin-producing Escherichia coli. Microbiol. Spectr. 2: EHEC-0027-2014.
- Espinosa L, Gray A, Duffy G, Fanning S, McMahon BJ. 2018. A scoping review on the prevalence of Shiga-toxigenic Escherichia coli in wild animal species. Zoonoses Public Health 65: 911-920. https://doi.org/10.1111/zph.12508
- Kim JS, Lee MS, Kim JH. 2020. Recent updates on outbreaks of Shiga toxin-producing Escherichia coli and its potential reservoirs. Front. Cell Infect. Microbiol. 10: 273.
- LeJeune JT, Besser TE, Merrill NL, Rice DH, Hancock DD. 2001. Livestock drinking water microbiology and the factors influencing the quality of drinking water offered to cattle. J. Dairy Sci. 84: 1856-1862. https://doi.org/10.3168/jds.S0022-0302(01)74626-7
- Caprioli A, Morabito S, Brugere H, Oswald E. 2005. Enterohaemorrhagic Escherichia coli: emerging issues on virulence and modes of transmission. Vet. Res. 36: 289-311. https://doi.org/10.1051/vetres:2005002
- Gyles CL. 2007. Shiga toxin-producing Escherichia coli: an overview. J. Anim. Sci. 85: E45-62. https://doi.org/10.2527/jas.2006-508
- Ferens WA, Hovde CJ. 2011. Escherichia coli O157:H7: animal reservoir and sources of human infection. Foodborne Pathog. Dis. 8: 465-487. https://doi.org/10.1089/fpd.2010.0673
- Pruimboom-Brees IM, Morgan TW, Ackermann MR, Nystrom ED, Samuel JE, Cornick NA, et al. 2000. Cattle lack vascular receptors for Escherichia coli O157:H7 Shiga toxins. Proc. Natl. Acad. Sci. USA 97: 10325-10329. https://doi.org/10.1073/pnas.190329997
- Galiero G, Conedera G, Alfano D, Caprioli A. 2005. Isolation of verocytotoxin-producing Escherichia coli O157 from water buffaloes (Bubalus bubalis) in southern Italy. Vet. Rec. 156: 382-383. https://doi.org/10.1136/vr.156.12.382
- French E, Rodriguez-Palacios A, LeJeune JT. 2010. Enteric bacterial pathogens with zoonotic potential isolated from farm-raised deer. Foodborne Pathog. Dis. 7: 1031-1037. https://doi.org/10.1089/fpd.2009.0486
- Chandran A, Mazumder A. 2013. Prevalence of diarrhea-associated virulence genes and genetic diversity in Escherichia coli isolates from fecal material of various animal hosts. Appl. Environ. Microbiol. 79: 7371-7380. https://doi.org/10.1128/AEM.02653-13
- Mohammed Hamzah A, Mohammed Hussein A, Mahmoud Khalef J. 2013. Isolation of Escherichia coli 0157:H7 strain from fecal samples of zoo animal. ScientificWorldJ. 2013: 843968.
- Nyholm O, Heinikainen S, Pelkonen S, Hallanvuo S, Haukka K, Siitonen A. 2015. Hybrids of shigatoxigenic and enterotoxigenic Escherichia coli (STEC/ETEC) among human and animal isolates in Finland. Zoonoses Public Health 62: 518-524. https://doi.org/10.1111/zph.12177
- Beutin L, Geier D, Steinrϋck H, Zimmermann S, Scheutz F. 1993. Prevalence and some properties of verotoxin (Shiga-like toxin)-producing Escherichia coli in seven different species of healthy domestic animals. J. Clin. Microbiol. 31: 2483-2488. https://doi.org/10.1128/jcm.31.9.2483-2488.1993
- DeVinney R, Stein M, Reinscheid D, Abe A, Ruschkowski S, Finlay BB. 1999. Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated. Infect. Immun. 67: 2389-2398. https://doi.org/10.1128/iai.67.5.2389-2398.1999
- Jerse AE, Yu J, Tall BD, Kaper JB. 1990. A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells. Proc. Natl. Acad. Sci. USA 87: 7839-7843. https://doi.org/10.1073/pnas.87.20.7839
- Kenny B, DeVinney R, Stein M, Reinscheid DJ, Frey EA, Finlay BB. 1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91: 511-520. https://doi.org/10.1016/S0092-8674(00)80437-7
- Nagy B, Fekete PZ. 2005. Enterotoxigenic Escherichia coli in veterinary medicine. Int. J. Med. Microbiol. 295: 443-454. https://doi.org/10.1016/j.ijmm.2005.07.003
- Melton-Celsa AR. 2014. Shiga Toxin (Stx) csification, structure, and function. Microbiol. Spectr. 2: EHEC-0024-2013.
- Plunkett G, 3rd, Rose DJ, Durfee TJ, Blattner FR. 1999. Sequence of Shiga toxin 2 phage 933W from Escherichia coli O157:H7: Shiga toxin as a phage late-gene product. J. Bacteriol. 181: 1767-1778. https://doi.org/10.1128/jb.181.6.1767-1778.1999
- Krϋger A, Lucchesi PM. 2015. Shiga toxins and stx phages: highly diverse entities. Microbiology (Reading) 161: 451-462. https://doi.org/10.1099/mic.0.000003
- Coburn B, Sekirov I, Finlay BB. 2007. Type III secretion systems and disease. Clin. Microbiol. Rev. 20: 535-549. https://doi.org/10.1128/CMR.00013-07
- McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB. 1995. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc. Natl. Acad. Sci. USA 92: 1664-1668. https://doi.org/10.1073/pnas.92.5.1664
- Dean P, Kenny B. 2009. The effector repertoire of enteropathogenic E. coli: ganging up on the host cell. Curr. Opin. Microbiol. 12: 101-109. https://doi.org/10.1016/j.mib.2008.11.006
- Brunder W, Schmidt H, Karch H. 1996. KatP, a novel catalaseperoxidase encoded by the large plasmid of enterohaemorrhagic Escherichia coli O157:H7. Microbiology (Reading) 142 (Pt 11): 3305-3315. https://doi.org/10.1099/13500872-142-11-3305
- Brunder W, Schmidt H, Karch H. 1997. EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V. Mol. Microbiol. 24: 767-778. https://doi.org/10.1046/j.1365-2958.1997.3871751.x
- Scheutz F, Teel LD, Beutin L, Pierard D, Buvens G, Karch H, et al. 2012. Multicenter evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J. Clin. Microbiol. 50: 2951-2963. https://doi.org/10.1128/JCM.00860-12
- Bai X, Fu S, Zhang J, Fan R, Xu Y, Sun H, et al. 2018. Identification and pathogenomic analysis of an Escherichia coli strain producing a novel Shiga toxin 2 subtype. Sci. Rep. 8: 6756.
- Lacher DW, Gangiredla J, Patel I, Elkins CA, Feng PC. 2016. Use of the Escherichia coli identification microarray for characterizing the health risks of Shiga toxin-producing Escherichia coli Isolated from foods. J. Food Prot. 79: 1656-1662. https://doi.org/10.4315/0362-028X.JFP-16-176
- Fao/Who Stec Expert G. 2019. Hazard identification and characterization: Criteria for categorizing Shiga toxin-producing Escherichia coli on a risk basis(dagger). J. Food Prot. 82: 7-21. https://doi.org/10.4315/0362-028x.jfp-18-291
- Ng TB, Wong JH, Wang H. 2010. Recent progress in research on ribosome inactivating proteins. Curr. Protein Pept. Sci. 11: 37-53. https://doi.org/10.2174/138920310790274662
- Endo Y, Tsurugi K, Yutsudo T, Takeda Y, Ogasawara T, Igarashi K. 1988. Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins. Eur. J. Biochem. 171: 45-50. https://doi.org/10.1111/j.1432-1033.1988.tb13756.x
- Ling H, Boodhoo A, Hazes B, Cummings MD, Armstrong GD, Brunton JL, et al. 1998. Structure of the shiga-like toxin I Bpentamer complexed with an analogue of its receptor Gb3. Biochemistry 37: 1777-1788. https://doi.org/10.1021/bi971806n
- Stahl AL, Arvidsson I, Johansson KE, Chromek M, Rebetz J, Loos S, et al. 2015. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles. PLoS Pathog. 11: e1004619.
- Watanabe-Takahashi M, Yamasaki S, Murata M, Kano F, Motoyama J, Yamate J, et al. 2018. Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice. Sci. Rep. 8: 10776.
- Brigotti M, Carnicelli D, Arfilli V, Tamassia N, Borsetti F, Fabbri E, et al. 2013. Identification of TLR4 as the receptor that recognizes Shiga toxins in human neutrophils. J. Immunol. 191: 4748-4758. https://doi.org/10.4049/jimmunol.1300122
- Schϋller S, Heuschkel R, Torrente F, Kaper JB, Phillips AD. 2007. Shiga toxin binding in normal and inflamed human intestinal mucosa. Microbes Infect. 9: 35-39. https://doi.org/10.1016/j.micinf.2006.10.005
- Zoja C, Morigi M, Remuzzi G. 2001. The role of the endothelium in hemolytic uremic syndrome. J. Nephrol. 14 Suppl 4: S58-62.
- Goldstein J, Loidl CF, Creydt VP, Boccoli J, Ibarra C. 2007. Intracerebroventricular administration of Shiga toxin type 2 induces striatal neuronal death and glial alterations: an ultrastructural study. Brain Res. 1161: 106-115. https://doi.org/10.1016/j.brainres.2007.05.067
- Obrig TG. 2010. Escherichia coli Shiga toxin mechanisms of action in renal disease. Toxins (Basel) 2: 2769-2794. https://doi.org/10.3390/toxins2122769
- Bosse M, Sibold J, Scheidt HA, Patalag LJ, Kettelhoit K, Ries A, et al. 2019. Shiga toxin binding alters lipid packing and the domain structure of Gb3-containing membranes: a solid-state NMR study. Phys. Chem. Chem. Phys. 21: 15630-15638. https://doi.org/10.1039/c9cp02501d
- Okuda T, Tokuda N, Numata S, Ito M, Ohta M, Kawamura K, et al. 2006. Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J. Biol. Chem. 281: 10230-10235. https://doi.org/10.1074/jbc.M600057200
- van de Kar NC, Monnens LA, Karmali MA, van Hinsbergh VW. 1992. Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood 80: 2755-2764. https://doi.org/10.1182/blood.v80.11.2755.2755
- Zumbrun SD, Melton-Celsa AR, Smith MA, Gilbreath JJ, Merrell DS, O'Brien AD. 2013. Dietary choice affects Shiga toxin-producing Escherichia coli (STEC) O157:H7 colonization and disease. Proc. Natl. Acad. Sci. USA 110: E2126-2133.
- Sandvig K, Olsnes S, Brown JE, Petersen OW, van Deurs B. 1989. Endocytosis from coated pits of Shiga toxin: a glycolipid-binding protein from Shigella dysenteriae 1. J. Cell Biol. 108: 1331-1343. https://doi.org/10.1083/jcb.108.4.1331
- Lauvrak SU, Walchli S, Iversen TG, Slagsvold HH, Torgersen ML, Spilsberg B, et al. 2006. Shiga toxin regulates its entry in a Syk-dependent manner. Mol. Biol. Cell 17: 1096-1109. https://doi.org/10.1091/mbc.E05-08-0766
- Torgersen ML, Lauvrak SU, Sandvig K. 2005. The A-subunit of surface-bound Shiga toxin stimulates clathrin-dependent uptake of the toxin. FEBS J. 272: 4103-4113. https://doi.org/10.1111/j.1742-4658.2005.04835.x
- Lauvrak SU, Torgersen ML, Sandvig K. 2004. Efficient endosome-to-Golgi transport of Shiga toxin is dependent on dynamin and clathrin. J. Cell Sci. 117: 2321-2331. https://doi.org/10.1242/jcs.01081
- Saint-Pol A, Yelamos B, Amessou M, Mills IG, Dugast M, Tenza D, et al. 2004. Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes. Dev. Cell 6: 525-538. https://doi.org/10.1016/S1534-5807(04)00100-5
- Renard HF, Garcia-Castillo MD, Chambon V, Lamaze C, Johannes L. 2015. Shiga toxin stimulates clathrin-independent endocytosis of the VAMP2, VAMP3 and VAMP8 SNARE proteins. J. Cell Sci. 128: 2891-2902. https://doi.org/10.1242/jcs.171116
- Malyukova I, Murray KF, Zhu C, Boedeker E, Kane A, Patterson K, et al. 2009. Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G78-92. https://doi.org/10.1152/ajpgi.90347.2008
- Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR. 1993. Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 12: 677-682. https://doi.org/10.1002/j.1460-2075.1993.tb05701.x
- Itin C, Rancano C, Nakajima Y, Pfeffer SR. 1997. A novel assay reveals a role for soluble N-ethylmaleimide-sensitive fusion attachment protein in mannose 6-phosphate receptor transport from endosomes to the trans Golgi network. J. Biol. Chem. 272: 27737-27744. https://doi.org/10.1074/jbc.272.44.27737
- Itin C, Ulitzur N, Mϋhlbauer B, Pfeffer SR. 1999. Mapmodulin, cytoplasmic dynein, and microtubules enhance the transport of mannose 6-phosphate receptors from endosomes to the trans-golgi network. Mol. Biol. Cell 10: 2191-2197. https://doi.org/10.1091/mbc.10.7.2191
- Miwako I, Yamamoto A, Kitamura T, Nagayama K, Ohashi M. 2001. Cholesterol requirement for cation-independent mannose 6-phosphate receptor exit from multivesicular late endosomes to the Golgi. J. Cell Sci. 114: 1765-1776. https://doi.org/10.1242/jcs.114.9.1765
- Iversen TG, Skretting G, Llorente A, Nicoziani P, van Deurs B, Sandvig K. 2001. Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9- and Rab11-GTPases. Mol. Biol. Cell 12: 2099-2107. https://doi.org/10.1091/mbc.12.7.2099
- Sandvig K, Grimmer S, Lauvrak SU, Torgersen ML, Skretting G, van Deurs B, et al. 2002. Pathways followed by ricin and Shiga toxin into cells. Histochem. Cell Biol. 117: 131-141. https://doi.org/10.1007/s00418-001-0346-2
- Lauvrak SU, Llorente A, Iversen TG, Sandvig K. 2002. Selective regulation of the Rab9-independent transport of ricin to the Golgi apparatus by calcium. J. Cell Sci. 115: 3449-3456. https://doi.org/10.1242/jcs.115.17.3449
- Mallard F, Antony C, Tenza D, Salamero J, Goud B, Johannes L. 1998. Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of shiga toxin B-fragment transport. J. Cell Biol. 143: 973-990. https://doi.org/10.1083/jcb.143.4.973
- Wilcke M, Johannes L, Galli T, Mayau V, Goud B, Salamero J. 2000. Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network. J. Cell Biol. 151: 1207-1220. https://doi.org/10.1083/jcb.151.6.1207
- Utskarpen A, Slagsvold HH, Dyve AB, Skanland SS, Sandvig K. 2007. SNX1 and SNX2 mediate retrograde transport of Shiga toxin. Biochem. Biophys. Res. Commun. 358: 566-570. https://doi.org/10.1016/j.bbrc.2007.04.159
- Johannes L, Popoff V. 2008. Tracing the retrograde route in protein trafficking. Cell 135: 1175-1187. https://doi.org/10.1016/j.cell.2008.12.009
- Jackson ME, Simpson JC, Girod A, Pepperkok R, Roberts LM, Lord JM. 1999. The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum. J. Cell Sci. 112 (Pt 4): 467-475. https://doi.org/10.1242/jcs.112.4.467
- White J, Johannes L, Mallard F, Girod A, Grill S, Reinsch S, et al. 1999. Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells. J.Cell Biol. 147: 743-760. https://doi.org/10.1083/jcb.147.4.743
- Girod A, Storrie B, Simpson JC, Johannes L, Goud B, Roberts LM, et al. 1999. Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum. Nat. Cell Biol. 1: 423-430. https://doi.org/10.1038/15658
- Chan YS, Ng TB. 2016. Shiga toxins: from structure and mechanism to applications. Appl. Microbiol. Biotechnol. 100: 1597-1610. https://doi.org/10.1007/s00253-015-7236-3
- Amessou M, Carrez D, Patin D, Sarr M, Grierson DS, Croisy A, et al. 2008. Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)3 selectively potentiates its photodynamic activity. Bioconjug. Chem. 19: 532-538. https://doi.org/10.1021/bc7003999
- Garred O, Dubinina E, Polesskaya A, Olsnes S, Kozlov J, Sandvig K. 1997. Role of the disulfide bond in Shiga toxin A-chain for toxin entry into cells. J. Biol. Chem. 272: 11414-11419. https://doi.org/10.1074/jbc.272.17.11414
- Nowakowska-Golacka J, Sominka H, Sowa-Rogozinska N, Slominska-Wojewodzka M. 2019. Toxins utilize the endoplasmic reticulum-associated protein degradation pathway in their intoxication process. Int. J. Mol. Sci. 20: 1307.
- Yu M, Haslam DB. 2005. Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/ERdj3. Infect. Immun. 73: 2524-2532. https://doi.org/10.1128/IAI.73.4.2524-2532.2005
- Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35: 495-516. https://doi.org/10.1080/01926230701320337
- Ching JC, Jones NL, Ceponis PJ, Karmali MA, Sherman PM. 2002. Escherichia coli shiga-like toxins induce apoptosis and cleavage of poly(ADP-ribose) polymerase via in vitro activation of caspases. Infect. Immun. 70: 4669-4677. https://doi.org/10.1128/IAI.70.8.4669-4677.2002
- Tang B, Li Q, Zhao XH, Wang HG, Li N, Fang Y, et al. 2015. Shiga toxins induce autophagic cell death in intestinal epithelial cells via the endoplasmic reticulum stress pathway. Autophagy 11: 344-354. https://doi.org/10.1080/15548627.2015.1023682
- Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, et al. 2019. A comprehensive review on MAPK: A promising therapeutic target in cancer. Cancers (Basel) 11: 1618.
- Kyriakis JM, Avruch J. 2001. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81: 807-869. https://doi.org/10.1152/physrev.2001.81.2.807
- Wada T, Penninger JM. 2004. Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23: 2838-2849. https://doi.org/10.1038/sj.onc.1207556
- Smith WE, Kane AV, Campbell ST, Acheson DW, Cochran BH, Thorpe CM. 2003. Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells. Infect. Immun. 71: 1497-1504. https://doi.org/10.1128/IAI.71.3.1497-1504.2003
- Cherla RP, Lee SY, Mees PL, Tesh VL. 2006. Shiga toxin 1-induced cytokine production is mediated by MAP kinase pathways and translation initiation factor eIF4E in the macrophage-like THP-1 cell line. J. Leukoc. Biol. 79: 397-407. https://doi.org/10.1189/jlb.0605313
- Jandhyala DM, Ahluwalia A, Obrig T, Thorpe CM. 2008. ZAK: a MAP3Kinase that transduces Shiga toxin and ricin-induced proinflammatory cytokine expression. Cell Microbiol. 10: 1468-1477. https://doi.org/10.1111/j.1462-5822.2008.01139.x
- Ketelut-Carneiro N, Fitzgerald KA. 2022. Apoptosis, pyroptosis, and necroptosis-oh my! the many ways a cell can die. J. Mol. Biol. 434: 167378.
- Coll RC, Schroder K, Pelegrin P. 2022. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol. Sci. 43: 653-668. https://doi.org/10.1016/j.tips.2022.04.003
- Platnich JM, Chung H, Lau A, Sandall CF, Bondzi-Simpson A, Chen HM, et al. 2018. Shiga toxin/lipopolysaccharide activates caspase-4 and gasdermin D to trigger mitochondrial reactive oxygen species upstream of the NLRP3 inflammasome. Cell Rep. 25: 1525-1536 e1527.
- Pinatih KJP, Suardana IW, Widiasih DA, Suharsono H. 2021. Shiga-like toxin produced by local isolates of Escherichia coli O157:H7 induces apoptosis of the T47 breast cancer cell line. Breast Cancer (Auckl) 15: 11782234211010120.
- Kim I, Xu W, Reed JC. 2008. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7: 1013-1030. https://doi.org/10.1038/nrd2755
- Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, et al. 2002. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415: 92-96. https://doi.org/10.1038/415092a
- Lee AH, Iwakoshi NN, Glimcher LH. 2003. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell Biol. 23: 7448-7459. https://doi.org/10.1128/MCB.23.21.7448-7459.2003
- Hetz C. 2012. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell Biol. 13: 89-102. https://doi.org/10.1038/nrm3270
- Lee SY, Lee MS, Cherla RP, Tesh VL. 2008. Shiga toxin 1 induces apoptosis through the endoplasmic reticulum stress response in human monocytic cells. Cell. Microbiol. 10: 770-780. https://doi.org/10.1111/j.1462-5822.2007.01083.x
- Lee KS, Lee J, Lee P, Jeon BC, Song MY, Kwak S, et al. 2022. Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host. EMBO Mol. Med. 14: e14678.
- Parello CS, Mayer CL, Lee BC, Motomochi A, Kurosawa S, Stearns-Kurosawa DJ. 2015. Shiga toxin 2-induced endoplasmic reticulum stress is minimized by activated protein C but does not correlate with lethal kidney injury. Toxins (Basel) 7: 170-186. https://doi.org/10.3390/toxins7010170
- Coe H, Michalak M. 2009. Calcium binding chaperones of the endoplasmic reticulum. Gen. Physiol. Biophys. 28 Spec No Focus: F96-F103.
- Kuznetsov G, Brostrom MA, Brostrom CO. 1992. Demonstration of a calcium requirement for secretory protein processing and export. Differential effects of calcium and dithiothreitol. J. Biol. Chem. 267: 3932-3939. https://doi.org/10.1016/S0021-9258(19)50615-9
- Sattler R, Tymianski M. 2000. Molecular mechanisms of calcium-dependent excitotoxicity. J. Mol. Med. (Berl). 78: 3-13. https://doi.org/10.1007/s001090000077
- Johansson KE, Stahl AL, Arvidsson I, Loos S, Tontanahal A, Rebetz J, et al. 2019. Shiga toxin signals via ATP and its effect is blocked by purinergic receptor antagonism. Sci. Rep. 9: 14362.
- Kostova EB, Beuger BM, Klei TR, Halonen P, Lieftink C, Beijersbergen R, et al. 2015. Identification of signalling cascades involved in red blood cell shrinkage and vesiculation. Biosci. Rep. 35: e00187.
- Liu R, Klich I, Ratajczak J, Ratajczak MZ, Zuba-Surma EK. 2009. Erythrocyte-derived microvesicles may transfer phosphatidylserine to the surface of nucleated cells and falsely 'mark' them as apoptotic. Eur. J. Haematol. 83: 220-229. https://doi.org/10.1111/j.1600-0609.2009.01271.x
- Majka M, Kijowski J, Lesko E, Gozdizk J, Zupanska B, Ratajczak MZ. 2007. Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34+ hematopoietic stem/progenitor cells--implication for the pathogenesis of immune thrombocytopenias. Folia Histochem. Cytobiol. 45: 27-32.
- Janowska-Wieczorek A, Majka M, Kijowski J, Baj-Krzyworzeka M, Reca R, Turner AR, et al. 2001. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 98: 3143-3149. https://doi.org/10.1182/blood.V98.10.3143
- Tkach M, Kowal J, Zucchetti AE, Enserink L, Jouve M, Lankar D, et al. 2017. Qualitative differences in T-cell activation by dendritic cell-derived extracellular vesicle subtypes. EMBO J. 36: 3012-3028. https://doi.org/10.15252/embj.201696003
- Cho BS, Kim JO, Ha DH, Yi YW. 2018. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res. Ther. 9: 187.
- van Niel G, D'Angelo G, Raposo G. 2018. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19: 213-228. https://doi.org/10.1038/nrm.2017.125
- He C, Hu X, Weston TA, Jung RS, Sandhu J, Huang S, et al. 2018. Macrophages release plasma membrane-derived particles rich in accessible cholesterol. Proc. Natl. Acad. Sci. USA 115: E8499-E8508.
- Kim KM, Abdelmohsen K, Mustapic M, Kapogiannis D, Gorospe M. 2017. RNA in extracellular vesicles. Wiley Interdiscip Rev. RNA. 8: 10.1002/wrna.1413. doi: 10.1002/wrna.1413.
- Latifkar A, Hur YH, Sanchez JC, Cerione RA, Antonyak MA. 2019. New insights into extracellular vesicle biogenesis and function. J. Cell Sci. 132: jcs222406.
- Stahl AL, Sartz L, Nelsson A, Bekassy ZD, Karpman D. 2009. Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome. PLoS One 4: e6990.
- Arvidsson I, Stahl AL, Hedstrom MM, Kristoffersson AC, Rylander C, Westman JS, et al. 2015. Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome. J. Immunol. 194: 2309-2318. https://doi.org/10.4049/jimmunol.1402470
- Ge S, Hertel B, Emden SH, Beneke J, Menne J, Haller H, von Vietinghoff S. 2012. Microparticle generation and leucocyte death in Shiga toxin-mediated HUS. Nephrol. Dial. Transplant. 27: 2768-2775. https://doi.org/10.1093/ndt/gfr748
- Iordanov MS, Pribnow D, Magun JL, Dinh TH, Pearson JA, Chen SL, et al. 1997. Ribotoxic stress response: activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol. Cell Biol. 17: 3373-3381. https://doi.org/10.1128/MCB.17.6.3373
- Lee MS, Cherla RP, Leyva-Illades D, Tesh VL. 2009. Bcl-2 regulates the onset of shiga toxin 1-induced apoptosis in THP-1 cells. Infect. Immun. 77: 5233-5244. https://doi.org/10.1128/IAI.00665-09
- Lim HS, Kim YJ, Kim BY, Park G, Jeong SJ. 2018. The anti-neuroinflammatory activity of tectorigenin pretreatment via downregulated NF-kappaB and ERK/JNK pathways in BV-2 microglial and microglia inactivation in mice with lipopolysaccharide. Front. Pharmacol. 9: 462.
- Gray JS, Bae HK, Li JC, Lau AS, Pestka JJ. 2008. Double-stranded RNA-activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, Shiga toxin 1, and ricin in monocytes. Toxicol. Sci. 105: 322-330. https://doi.org/10.1093/toxsci/kfn128
- Elliott TS, Shelton A, Greenwood D. 1987. The response of Escherichia coli to ciprofloxacin and norfloxacin. J. Med. Microbiol. 23: 83-88. https://doi.org/10.1099/00222615-23-1-83
- Angel Villegas N, Baronetti J, Albesa I, Etcheverria A, Becerra MC, Padola NL, et al. 2015. Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms. Toxicol. In Vitro 29: 1692-1700. https://doi.org/10.1016/j.tiv.2015.06.025
- Ichinohe N, Ohara-Nemoto Y, Nemoto TK, Kimura S, Ichinohe S. 2009. Effects of fosfomycin on Shiga toxin-producing Escherichia coli: quantification of copy numbers of Shiga toxin-encoding genes and their expression levels using real-time PCR. J. Med. Microbiol. 58: 971-973. https://doi.org/10.1099/jmm.0.008573-0
- Griffin DE, Gentry MK, Brown JE. 1983. Isolation and characterization of monoclonal antibodies to Shiga toxin. Infect. Immun. 41: 430-433. https://doi.org/10.1128/iai.41.1.430-433.1983
- Strockbine NA, Marques LR, Holmes RK, O'Brien AD. 1985. Characterization of monoclonal antibodies against Shiga-like toxin from Escherichia coli. Infect. Immun. 50: 695-700. https://doi.org/10.1128/iai.50.3.695-700.1985
- Melton-Celsa A, Mohawk K, Teel L, O'Brien A. 2012. Pathogenesis of Shiga-toxin producing escherichia coli. Curr. Top. Microbiol. Immunol. 357: 67-103. https://doi.org/10.1007/82_2011_176
- Cheng LW, Henderson TD, Patfield S, Stanker LH, He X. 2013. Mouse in vivo neutralization of Escherichia coli Shiga toxin 2 with monoclonal antibodies. Toxins (Basel) 5: 1845-1858. https://doi.org/10.3390/toxins5101845
- Smith MJ, Melton-Celsa AR, Sinclair JF, Carvalho HM, Robinson CM, O'Brien AD. 2009. Monoclonal antibody 11E10, which neutralizes shiga toxin type 2 (Stx2), recognizes three regions on the Stx2 A subunit, blocks the enzymatic action of the toxin in vitro, and alters the overall cellular distribution of the toxin. Infect. Immun. 77: 2730-2740. https://doi.org/10.1128/IAI.00005-09
- Nakanishi K, Morikane S, Ichikawa S, Kurohane K, Niwa Y, Akimoto Y, et al. 2017. Protection of human colon cells from Shiga toxin by plant-based recombinant secretory IgA. Sci. Rep. 7: 45843.
- Ruano-Gallego D, Yara DA, Di Ianni L, Frankel G, Schϋller S, Fernandez LA. 2019. A nanobody targeting the translocated intimin receptor inhibits the attachment of enterohemorrhagic E. coli to human colonic mucosa. PLoS Pathog. 15: e1008031.
- Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DW, et al. 2003. Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial. JAMA 290: 1337-1344. https://doi.org/10.1001/jama.290.10.1337
- Nishikawa K, Matsuoka K, Kita E, Okabe N, Mizuguchi M, Hino K, et al. 2002. A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli O157:H7. Proc. Natl. Acad. Sci. USA 99: 7669-7674. https://doi.org/10.1073/pnas.112058999
- Nishikawa K, Matsuoka K, Watanabe M, Igai K, Hino K, Hatano K, et al. 2005. Identification of the optimal structure required for a Shiga toxin neutralizer with oriented carbohydrates to function in the circulation. J. Infect. Dis. 191: 2097-2105. https://doi.org/10.1086/430388
- Watanabe M, Matsuoka K, Kita E, Igai K, Higashi N, Miyagawa A, et al. 2004. Oral therapeutic agents with highly clustered globotriose for treatment of Shiga toxigenic Escherichia coli infections. J. Infect. Dis. 189: 360-368. https://doi.org/10.1086/381124
- LaCasse EC, Bray MR, Patterson B, Lim WM, Perampalam S, Radvanyi LG, et al. 1999. Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation. Blood 94: 2901-2910.
- Arab S, Russel E, Chapman WB, Rosen B, Lingwood CA. 1997. Expression of the verotoxin receptor glycolipid, globotriaosylceramide, in ovarian hyperplasias. Oncol. Res. 9: 553-563.
- Maak M, Nitsche U, Keller L, Wolf P, Sarr M, Thiebaud M, et al. 2011. Tumor-specific targeting of pancreatic cancer with Shiga toxin B-subunit. Mol. Cancer Ther. 10: 1918-1928. https://doi.org/10.1158/1535-7163.MCT-11-0006
- Ohyama C, Fukushi Y, Satoh M, Saitoh S, Orikasa S, Nudelman E, et al. 1990. Changes in glycolipid expression in human testicular tumor. Int. J. Cancer 45: 1040-1044. https://doi.org/10.1002/ijc.2910450610
- El Alaoui A, Schmidt F, Amessou M, Sarr M, Decaudin D, Florent JC, et al. 2007. Shiga toxin-mediated retrograde delivery of a topoisomerase I inhibitor prodrug. Angew. Chem. Int. Ed. Engl. 46: 6469-6472. https://doi.org/10.1002/anie.200701270
- El Alaoui A, Schmidt F, Sarr M, Decaudin D, Florent JC, Johannes L. 2008. Synthesis and properties of a mitochondrial peripheral benzodiazepine receptor conjugate. ChemMedChem. 3: 1687-1695. https://doi.org/10.1002/cmdc.200800249
- Farkas-Himsley H, Hill R, Rosen B, Arab S, Lingwood CA. 1995. The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1. Proc. Natl. Acad. Sci. USA 92: 6996-7000. https://doi.org/10.1073/pnas.92.15.6996
- Salhia B, Rutka JT, Lingwood C, Nutikka A, Van Furth WR. 2002. The treatment of malignant meningioma with verotoxin. Neoplasia 4: 304-311. https://doi.org/10.1038/sj.neo.7900243
- Heath-Engel HM, Lingwood CA. 2003. Verotoxin sensitivity of ECV304 cells in vitro and in vivo in a xenograft tumour model: VT1 as a tumour neovascular marker. Angiogenesis 6: 129-141. https://doi.org/10.1023/B:AGEN.0000011799.47529.fd
- Ishitoya S, Kurazono H, Nishiyama H, Nakamura E, Kamoto T, Habuchi T, et al. 2004. Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice. J. Urol. 171: 1309-1313. https://doi.org/10.1097/01.ju.0000100110.11129.85
- Arab S, Rutka J, Lingwood C. 1999. Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice. Oncol. Res. 11: 33-39.
- Palermo MS, Exeni RA, Fernandez GC. 2009. Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev. Anti. Infect. Ther. 7: 697-707. https://doi.org/10.1586/eri.09.49
- Lee MS, Kwon H, Lee EY, Kim DJ, Park JH, Tesh VL, et al. 2016. Shiga toxins activate the NLRP3 inflammasome pathway to promote both production of the proinflammatory cytokine interleukin-1beta and apoptotic cell death. Infect. Immun. 84: 172-186. https://doi.org/10.1128/IAI.01095-15
- Shu Q, Gill HS. 2002. Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20) against Escherichia coli O157:H7 infection in mice. FEMS Immunol. Med. Microbiol. 34: 59-64. https://doi.org/10.1111/j.1574-695X.2002.tb00603.x
- Shu Q, Gill HS. 2001. A dietary probiotic (Bifidobacterium lactis HN019) reduces the severity of Escherichia coli O157:H7 infection in mice. Med. Microbiol. Immunol. 189: 147-152. https://doi.org/10.1007/s430-001-8021-9