Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
권호 표지
DOI QR코드

DOI QR Code

Physiological understanding of host-microbial pathogen interactions in the gut

  • Lee, Sei-Jung (Department of Veterinary Physiology, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Research, College of Veterinary Medicine) ;
  • Choi, Sang Ho (National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University) ;
  • Han, Ho Jae (Department of Veterinary Physiology, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Research, College of Veterinary Medicine)
  • Received : 2016.03.14
  • Accepted : 2016.04.29
  • Published : 2016.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The gut epithelial barrier, which is composed of the mucosal layer and the intestinal epithelium, has multiple defense mechanisms and interconnected regulatory mechanisms against enteric microbial pathogens. However, many bacterial pathogens have highly evolved infectious stratagems that manipulate mucin production, epithelial cell-cell junctions, cell death, and cell turnover to promote their replication and pathogenicity in the gut epithelial barrier. In this review, we focus on current knowledge about how bacterial pathogens regulate mucin levels to circumvent the epithelial mucus barrier and target cell-cell junctions to invade deeper tissues and increase their colonization. We also describe how bacterial pathogens manipulate various modes of epithelial cell death to facilitate bacterial dissemination and virulence effects. Finally, we discuss recent investigating how bacterial pathogens regulate epithelial cell turnover and intestinal stem cell populations to modulate intestinal epithelium homeostasis.

Keywords

References

  1. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003, 300, 1430-1434. https://doi.org/10.1126/science.1081919
  2. An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun J, Xia L. Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J Exp Med 2007, 204, 1417-1429. https://doi.org/10.1084/jem.20061929
  3. Arbeloa A, Garnett J, Lillington J, Bulgin RR, Berger CN, Lea SM, Matthews S, Frankel G. EspM2 is a RhoA guanine nucleotide exchange factor. Cell Microbiol 2010, 12, 654-664. https://doi.org/10.1111/j.1462-5822.2009.01423.x
  4. Ashida H, Mimuro H, Ogawa M, Kobayashi T, Sanada T, Kim M, Sasakawa C. Cell death and infection: a double-edged sword for host and pathogen survival. J Cell Biol 2011, 195, 931-942. https://doi.org/10.1083/jcb.201108081
  5. Ashida H, Mimuro H, Sasakawa C. Shigella manipulates host immune responses by delivering effector proteins with specific roles. Front Immunol 2015, 6, 219.
  6. Ashida H, Ogawa M, Kim M, Mimuro H, Sasakawa C. Bacteria and host interactions in the gut epithelial barrier. Nat Chem Biol 2012, 8, 36-45. https://doi.org/10.1038/nchembio.741
  7. Babbin BA, Sasaki M, Gerner-Schmidt KW, Nusrat A, Klapproth JM. The bacterial virulence factor lymphostatin compromises intestinal epithelial barrier function by modulating rho GTPases. Am J Pathol 2009, 174, 1347-1357. https://doi.org/10.2353/ajpath.2009.080640
  8. Bagnoli F, Buti L, Tompkins L, Covacci A, Amieva MR. Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. Proc Natl Acad Sci U S A 2005, 102, 16339-16344. https://doi.org/10.1073/pnas.0502598102
  9. Barbieri JT, Riese MJ, Aktories K. Bacterial toxins that modify the actin cytoskeleton. Annu Rev Cell Dev Biol 2002, 18, 315-344. https://doi.org/10.1146/annurev.cellbio.18.012502.134748
  10. Barbuddhe SB, Chakraborty T. Listeria as an enteroinvasive gastrointestinal pathogen. Curr Top Microbiol Immunol 2009, 337, 173-195.
  11. Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol 2014, 15, 19-33.
  12. Birmingham CL, Canadien V, Gouin E, Troy EB, Yoshimori T, Cossart P, Higgins DE, Brumell JH. Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy 2007, 3, 442-451. https://doi.org/10.4161/auto.4450
  13. Birmingham CL, Smith AC, Bakowski MA, Yoshimori T, Brumell JH. Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 2006, 281, 11374-11383. https://doi.org/10.1074/jbc.M509157200
  14. Biswas D, Qureshi OS, Lee WY, Croudace JE, Mura M, Lammas DA. ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunol 2008, 9, 35. https://doi.org/10.1186/1471-2172-9-35
  15. Brodsky IE, Palm NW, Sadanand S, Ryndak MB, Sutterwala FS, Flavell RA, Bliska JB, Medzhitov R. A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. Cell Host Microbe 2010, 7, 376-387. https://doi.org/10.1016/j.chom.2010.04.009
  16. Carneiro LAM, Travassos LH, Soares F, Tattoli I, Magalhaes JG, Bozza MT, Plotkowski MC, Sansonetti PJ, Molkentin JD, Philpott DJ, Girardin SE. Shigella induces mitochondrial dysfunction and cell death in nonmyleoid cells. Cell Host Microbe 2009, 5, 123-136. https://doi.org/10.1016/j.chom.2008.12.011
  17. Caron TJ, Scott KE, Fox JG, Hagen SJ. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier. World J Gastroenterol 2015, 21, 11411-11427. https://doi.org/10.3748/wjg.v21.i40.11411
  18. Cemma M, Brumell JH. Interactions of pathogenic bacteria with autophagy systems. Curr Biol 2012, 22, R540-R545. https://doi.org/10.1016/j.cub.2012.06.001
  19. Cheng L, Mirko R, Sara L, Medea P, Caroline B, Eva B, Myrthe J, Bram F, Wim VD, Richard D, Freddy H, Annemieke S. The Helicobacter heilmannii hofE and hofF genes are essential for colonization of the gastric mucosa and play a role in IL-$1{\beta}$-induced gastric MUC13 expression. Helicobacter 2016. Epub ahead of print. doi: 10.1111/hel.12307.
  20. Dharmani P, Srivastava V, Kissoon-Singh V, Chadee K. Role of intestinal mucins in innate host defense mechanisms against pathogens. J Innate Immun 2009, 1, 123-135. https://doi.org/10.1159/000163037
  21. Etzold S, Juge N. Structural insights into bacterial recognition of intestinal mucins. Curr Opin Struct Biol 2014, 28, 23-31. https://doi.org/10.1016/j.sbi.2014.07.002
  22. Fassino S, Svrakic D, Abbate-Daga G, Leombruni P, Amianto F, Stanic S, Rovera GG. Anorectic family dynamics: temperament and character data. Compr Psychiatry 2002, 43, 114-120. https://doi.org/10.1053/comp.2002.30806
  23. Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 2005, 73, 1907-1916. https://doi.org/10.1128/IAI.73.4.1907-1916.2005
  24. Finlay BB, Falkow S. Common themes in microbial pathogenicity revisited. Microbiol Mol Biol Rev 1997, 61, 136-169.
  25. Gopal A, Iyer SC, Gopal U, Devaraj N, Halagowder D. Shigella dysenteriae modulates BMP pathway to induce mucin gene expression in vivo and in vitro. PLoS One 2014, 9, e111408. https://doi.org/10.1371/journal.pone.0111408
  26. Gutierrez-Jimenez J, Arciniega I, Navarro-Garcia F. The serine protease motif of Pic mediates a dose-dependent mucolytic activity after binding to sugar constituents of the mucin substrate. Microb Pathog 2008, 45, 115-123. https://doi.org/10.1016/j.micpath.2008.04.006
  27. Hamada T, Goto M, Tsutsumida H, Nomoto M, Higashi M, Sugai T, Nakamura S, Yonezawa S. Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing. Cancer Lett 2005, 227, 175-184. https://doi.org/10.1016/j.canlet.2004.11.058
  28. Hansson GC. Role of mucus layers in gut infection and inflammation. Curr Opin Microbiol 2012, 15, 57-62. https://doi.org/10.1016/j.mib.2011.11.002
  29. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009, 43, 67-93. https://doi.org/10.1146/annurev-genet-102808-114910
  30. Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, Thornton DJ, Png CW, Crockford TL, Cornall RJ, Adams R, Kato M, Nelms KA, Hong NA, Florin TH, Goodnow CC, McGuckin MA. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med 2008, 5, e54. https://doi.org/10.1371/journal.pmed.0050054
  31. Hemrajani C, Berger CN, Robinson KS, Marches O, Mousnier A, Frankel G. NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection. Proc Natl Acad Sci U S A 2010, 107, 3129-3134. https://doi.org/10.1073/pnas.0911609106
  32. Hiyoshi H, Okada R, Matsuda S, Gotoh K, Akeda Y, Iida T, Kodama T. Interaction between the type III effector VopO and GEF-H1 activates the RhoA-ROCK pathway. PLoS Pathog 2015, 11, e1004694. https://doi.org/10.1371/journal.ppat.1004694
  33. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993, 75, 241-251. https://doi.org/10.1016/0092-8674(93)80066-N
  34. In J, Foulke-Abel J, Zachos NC, Hansen AM, Kaper JB, Bernstein HD, Halushka M, Blutt S, Estes MK, Donowitz M, Kovbasnjuk O. Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cell Mol Gastroenterol Hepatol 2016, 2, 48-62.e3. https://doi.org/10.1016/j.jcmgh.2015.10.001
  35. Jones RM, Wu H, Wentworth C, Luo L, Collier-Hyams L, Neish AS. Salmonella AvrA coordinates suppression of host immune and apoptotic defenses via JNK pathway blockade. Cell Host Microbe 2008, 3, 233-244. https://doi.org/10.1016/j.chom.2008.02.016
  36. Keilberg D, Ottemann KM. How Helicobacter pylori senses, targets, and interacts with the gastric epithelium. Environ Microbiol 2016, 18, 791-806. https://doi.org/10.1111/1462-2920.13222
  37. Ki MR, Lee HR, Goo MJ, Hong IH, Do SH, Jeong DH, Yang HJ, Yuan DW, Park JK, Jeong KS. Differential regulation of ERK1/2 and p38 MAP kinases in VacA-induced apoptosis of gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol 2008, 294, G635-647. https://doi.org/10.1152/ajpgi.00281.2007
  38. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290, 1717-1721. https://doi.org/10.1126/science.290.5497.1717
  39. Knodler LA, Finlay BB, Steele-Mortimer O. The Salmonella effector protein SopB protects epithelial cells from apoptosis by sustained activation of Akt. J Biol Chem 2005, 280, 9058-9064. https://doi.org/10.1074/jbc.M412588200
  40. Krokowski S, Mostowy S. Interactions between Shigella flexneri and the autophagy machinery. Front Cell Infect Microbiol 2016, 6, 17.
  41. Kusumoto K, Kawahara T, Kuwano Y, Teshima-Kondo S, Morita K, Kishi K, Rokutan K. Ecabet sodium inhibits Helicobacter pylori lipopolysaccharide-induced activation of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells. Am J Physiol Gastrointest Liver Physiol 2005, 288, G300-307. https://doi.org/10.1152/ajpgi.00274.2004
  42. Labbé K, Saleh M. Cell death in the host response to infection. Cell Death Differ 2008, 15, 1339-1349. https://doi.org/10.1038/cdd.2008.91
  43. Lapointe TK, O'Connor PM, Jones NL, Menard D, Buret AG. Interleukin-1 receptor phosphorylation activates Rho kinase to disrupt human gastric tight junctional claudin-4 during Helicobacter pylori infection. Cell Microbiol 2010, 12, 692-703. https://doi.org/10.1111/j.1462-5822.2010.01429.x
  44. Lee DBN, Jamgotchian N, Allen SG, Kan FWK, Hale IL. Annexin A2 heterotetramer: role in tight junction assembly. Am J Physiol Renal Physiol 2004, 287, F481-491. https://doi.org/10.1152/ajprenal.00175.2003
  45. Lee SJ, Jung YH, Oh SY, Jang KK, Lee HS, Choi SH, Han HJ. Vibrio vulnificus VvpE inhibits mucin 2 expression by hypermethylation via lipid raft-mediated ROS signaling in intestinal epithelial cells. Cell Death Dis 2015, 6, e1787. https://doi.org/10.1038/cddis.2015.152
  46. Lee SJ, Jung YH, Oh SY, Song EJ, Choi SH, Han HJ. Vibrio vulnificus VvhA induces NF-${\kappa}B$-dependent mitochondrial cell death via lipid raft-mediated ROS production in intestinal epithelial cells. Cell Death Dis 2015, 6, 1655. https://doi.org/10.1038/cddis.2015.19
  47. Lee SJ, Jung YH, Ryu JM, Jang KK, Choi SH, Han HJ. VvpE mediates the intestinal colonization of Vibrio vulnificus by the disruption of tight junctions. Int J Med Microbiol 2016, 306, 10-19. https://doi.org/10.1016/j.ijmm.2015.10.006
  48. Lee SJ, Jung YH, Song EJ, Jang KK, Choi SH, Han HJ. Vibrio vulnificus VvpE stimulates IL-$1{\beta}$ production by the hypomethylation of the IL-$1{\beta}$ promoter and NF-${\kappa}B$ activation via lipid raft-dependent ANXA2 recruitment and reactive oxygen species signaling in intestinal epithelial cells. J Immunol 2015, 195, 2282-2293. https://doi.org/10.4049/jimmunol.1500951
  49. Lee SJ, Leoni G, Neumann PA, Chun J, Nusrat A, Yun CC. Distinct phospholipase C-$\beta$ isozymes mediate lysophosphatidic acid receptor 1 effects on intestinal epithelial homeostasis and wound closure. Mol Cell Biol 2013, 33, 2016-2028. https://doi.org/10.1128/MCB.00038-13
  50. Lemjabbar H, Basbaum C. Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells. Nat Med 2002, 8, 41-46. https://doi.org/10.1038/nm0102-41
  51. Li JD, Feng W, Gallup M, Kim JH, Gum J, Kim Y, Basbaum C. Activation of NF-${\kappa}B$ via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci U S A 1998, 95, 5718-5723. https://doi.org/10.1073/pnas.95.10.5718
  52. Lu L, Walker WA. Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium. Am J Clin Nutr 2001, 73, 1124S-1130S. https://doi.org/10.1093/ajcn/73.6.1124S
  53. Maurer K, Torres VJ, Cadwell K. Autophagy is a key tolerance mechanism during Staphylococcus aureus infection. Autophagy 2015, 11, 1184-1186. https://doi.org/10.1080/15548627.2015.1058685
  54. McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, Florin TH, Hill GR, Korolik V, McGuckin MA. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest 2007, 117, 2313-2324. https://doi.org/10.1172/JCI26705
  55. Neish AS. Redox signaling mediated by the gut microbiota. Free Radic Res 2013, 47, 950-957. https://doi.org/10.3109/10715762.2013.833331
  56. Nigro G, Rossi R, Commere PH, Jay P, Sansonetti PJ. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 2014, 15, 792-798. https://doi.org/10.1016/j.chom.2014.05.003
  57. Nougayrede JP, Donnenberg MS. Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway. Cell Microbiol 2004, 6, 1097-1111. https://doi.org/10.1111/j.1462-5822.2004.00421.x
  58. Paesold G, Guiney DG, Eckmann L, Kagnoff MF. Genes in the Salmonella pathogenicity island 2 and the Salmonella virulence plasmid are essential for Salmonella-induced apoptosis in intestinal epithelial cells. Cell Microbiol 2002, 4, 771-781. https://doi.org/10.1046/j.1462-5822.2002.00233.x
  59. Parlato M, Yeretssian G. NOD-like receptors in intestinal homeostasis and epithelial tissue repair. Int J Mol Sci 2014, 15, 9594-9627. https://doi.org/10.3390/ijms15069594
  60. Pillai L, Sha J, Erova TE, Fadl AA, Khajanchi BK, Chopra AK. Molecular and functional characterization of a ToxR-regulated lipoprotein from a clinical isolate of Aeromonas hydrophila. Infect Immun 2006, 74, 3742-3755. https://doi.org/10.1128/IAI.00402-06
  61. Popoff MR, Geny B. Multifaceted role of Rho, Rac, Cdc42 and Ras in intercellular junctions, lessons from toxins. Biochim Biophys Acta 2009, 1788, 797-812. https://doi.org/10.1016/j.bbamem.2009.01.011
  62. Ribet D, Cossart P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect 2015, 17, 173-183. https://doi.org/10.1016/j.micinf.2015.01.004
  63. Ricci V, Ciacci C, Zarrilli R, Sommi P, Tummuru MK, Del Vecchio Blanco C, Bruni CB, Cover TL, Blaser MJ, Romano M. Effect of Helicobacter pylori on gastric epithelial cell migration and proliferation in vitro: role of VacA and CagA. Infect Immun 1996, 64, 2829-2833.
  64. Robinson K, Deng Z, Hou Y, Zhang G. Regulation of the Intestinal Barrier Function by Host Defense Peptides. Front Vet Sci 2015, 2, 57.
  65. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build cryptvillus structures in vitro without a mesenchymal niche. Nature 2009, 459, 262-265. https://doi.org/10.1038/nature07935
  66. Sauer JD, Witte CE, Zemansky J, Hanson B, Lauer P, Portnoy DA. Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe 2010, 7, 412-419. https://doi.org/10.1016/j.chom.2010.04.004
  67. Schauser K, Larsson LI. Programmed cell death and cell extrusion in rat duodenum: a study of expression and activation of caspase-3 in relation to C-jun phosphorylation, DNA fragmentation and apoptotic morphology. Histochem Cell Biol 2005, 124, 237-243. https://doi.org/10.1007/s00418-005-0035-7
  68. Schnaith A, Kashkar H, Leggio SA, Addicks K, Krönke M, Krut O. Staphylococcus aureus subvert autophagy for induction of caspase-independent host cell death. J Biol Chem 2007, 282, 2695-2706. https://doi.org/10.1074/jbc.M609784200
  69. Sears CL. Molecular physiology and pathophysiology of tight junctions V. Assault of the tight junction by enteric pathogens. Am J Physiol Gastrointest Liver Physiol 2000, 279, G1129-1134. https://doi.org/10.1152/ajpgi.2000.279.6.G1129
  70. Sellin JH, Wang Y, Singh P, Umar S. $\beta$-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia. Exp Cell Res 2009, 315, 97-109. https://doi.org/10.1016/j.yexcr.2008.10.019
  71. Shan M, Gentile M, Yeiser JR, Walland AC, Bornstein VU, Chen K, He B, Cassis L, Bigas A, Cols M, Comerma L, Huang B, Blander JM, Xiong H, Mayer L, Berin C, Augenlicht LH, Velcich A, Cerutti A. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 2013, 342, 447-453. https://doi.org/10.1126/science.1237910
  72. Sigal M, Rothenberg ME, Logan CY, Lee JY, Honaker RW, Cooper RL, Passarelli B, Camorlinga M, Bouley DM, Alvarez G, Nusse R, Torres J, Amieva MR. Helicobacter pylori activates and expands $Lgr5^+$ stem cells through direct colonization of the gastric glands. Gastroenterology 2015, 148, 1392-1404.e21. https://doi.org/10.1053/j.gastro.2015.02.049
  73. Silva AJ, Pham K, Benitez JA. Haemagglutinin/protease expression and mucin gel penetration in El Tor biotype Vibrio cholerae. Microbiology 2003, 149, 1883-1891. https://doi.org/10.1099/mic.0.26086-0
  74. Song EJ, Lee SJ, Lim HS, Kim JS, Jang KK, Choi SH, Han HJ. Vibrio vulnificus VvhA induces autophagy-related cell death through the lipid raft-dependent c-Src/NOX signaling pathway. Sci Rep 2016, 6, 27080 https://doi.org/10.1038/srep27080
  75. van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009, 71, 241-260. https://doi.org/10.1146/annurev.physiol.010908.163145
  76. van der Goot FG, Harder T. Raft membrane domains: from a liquid-ordered membrane phase to a site of pathogen attack. Semin Immunol 2001, 13, 89-97. https://doi.org/10.1006/smim.2000.0300
  77. Wang L, Cao H, Liu L, Wang B, Walker WA, Acra SA, Yan F. Activation of epidermal growth factor receptor mediates mucin production stimulated by p40, a Lactobacillus rhamnosus GG-derived protein. J Biol Chem 2014, 289, 20234-20244. https://doi.org/10.1074/jbc.M114.553800
  78. Wessler S, Backert S. Molecular mechanisms of epithelial-barrier disruption by Helicobacter pylori. Trends Microbiol 2008, 16, 397-405. https://doi.org/10.1016/j.tim.2008.05.005
  79. Williams JM, Duckworth CA, Burkitt MD, Watson AJM, Campbell BJ, Pritchard DM. Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip. Vet Pathol 2015, 52, 445-455. https://doi.org/10.1177/0300985814559404
  80. Wu HJ, Wang AHJ, Jennings MP. Discovery of virulence factors of pathogenic bacteria. Curr Opin Chem Biol 2008, 12, 93-101. https://doi.org/10.1016/j.cbpa.2008.01.023
  81. Wu S, Lim KC, Huang J, Saidi RF, Sears CL. Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci U S A 1998, 95, 14979-14984. https://doi.org/10.1073/pnas.95.25.14979
  82. Wu Z, Nybom P, Magnusson KE. Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1. Cell Microbiol 2000, 2, 11-17. https://doi.org/10.1046/j.1462-5822.2000.00025.x
  83. Yan F, Cao H, Chaturvedi R, Krishna U, Hobbs SS, Dempsey PJ, Peek RM Jr, Cover TL, Washington MK, Wilson KT, Polk DB. Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis. Gastroenterology 2009, 136, 1297-1307.e3. https://doi.org/10.1053/j.gastro.2008.12.059
  84. Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, Orth K. AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling. Science 2009, 323, 269-272. https://doi.org/10.1126/science.1166382
  85. Zarepour M, Bhullar K, Montero M, Ma C, Huang T, Velcich A, Xia L, Vallance BA. The mucin Muc2 limits pathogen burdens and epithelial barrier dysfunction during Salmonella enterica serovar Typhimurium colitis. Infect Immun 2013, 81, 3672-3683. https://doi.org/10.1128/IAI.00854-13
  86. Zobiack N, Rescher U, Laarmann S, Michgehl S, Schmidt MA, Gerke V. Cell-surface attachment of pedestal-forming enteropathogenic E. coli induces a clustering of raft components and a recruitment of annexin 2. J Cell Sci 2002, 115, 91-98.