Dynamic interactions of a conserved enterotoxigenic Escherichia coli adhesin with intestinal mucins govern epithelium engagement and toxin delivery

Infection and Immunity

Volumn 84, Issue 12, 2016, Pages 3608-3617

  Kumar, Pardeep ^a   Kuhlmann, F Matthew ^a   Bhullar, Kirandeep ^c   Yang, Hyungjun ^c   Vallance, Bruce A ^c   Xia, Lijun ^d   Luo, Qingwei ^a   Fleckenstein, James M ^a,b  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADHESIN; ESCHERICHIA ENTEROTOXIN; MUCIN 2; ESCHERICHIA COLI PROTEIN; ETPA PROTEIN, E COLI; MEMBRANE PROTEIN; MUC2 PROTEIN, MOUSE; MUCIN; N ACETYLGALACTOSAMINE;

ARTICLE; CELL SURFACE; CELL TRANSPORT; ENTEROTOXIGENIC ESCHERICHIA COLI; HOST PATHOGEN INTERACTION; HUMAN; HUMAN CELL; INTESTINE EPITHELIUM CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN SECRETION; ANIMAL; C57BL MOUSE; CACO-2 CELL LINE; GENETICS; HT-29 CELL LINE; INTESTINE MUCOSA; KNOCKOUT MOUSE; METABOLISM; MICROBIOLOGY; MOUSE; PHYSIOLOGY; RNA INTERFERENCE;

ACETYLGALACTOSAMINE; ADHESINS, BACTERIAL; ANIMALS; CACO-2 CELLS; ENTEROTOXIGENIC ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; HT29 CELLS; HUMANS; INTESTINAL MUCOSA; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUCIN-2; MUCINS; RNA INTERFERENCE;

EID: 85002836374     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00692-16     Document Type: Article

References (48)

1. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209-222. http://dx.doi.org/10.1016/S0140-6736(13)60844-2
2. Qadri F, Saha A, Ahmed T, Al Tarique A, Begum YA, Svennerholm AM. 2007. Disease burden due to enterotoxigenic Escherichia coli in the first 2 years of life in an urban community in Bangladesh. Infect Immun 75:3961-3968. http://dx.doi.org/10.1128/IAI.00459-07
3. Platts-Mills JA, Babji S, Bodhidatta L, Gratz J, Haque R, Havt A, McCormick BJ, McGrath M, Olortegui MP, Samie A, Shakoor S, Mondal D, Lima IF, Hariraju D, Rayamajhi BB, Qureshi S, Kabir F, Yori PP, Mufamadi B, Amour C, Carreon JD, Richard SA, Lang D, Bessong P, Mduma E, Ahmed T, Lima AA, Mason CJ, Zaidi AK, Bhutta ZA, Kosek M, Guerrant RL, Gottlieb M, Miller M, Kang G, Houpt ER, MAL-ED Network Investigators. 2015. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health 3:e564-575. http://dx.doi.org/10 .1016/S2214-109X(15)00151-5
4. Sack RB. 2011. The discovery of cholera-like enterotoxins produced by Escherichia coli causing secretory diarrhoea in humans. Indian J Med Res 133:171-180
5. Fleckenstein JM, Hardwidge PR, Munson GP, Rasko DA, Sommerfelt H, Steinsland H. 2010. Molecular mechanisms of enterotoxigenic Escherichia coli infection. Microbes Infect 12:89-98. http://dx.doi.org/10 .1016/j.micinf.2009.10.002
6. Svennerholm AM, Lundgren A. 2012. Recent progress toward an enterotoxigenic Escherichia coli vaccine. Expert Rev Vaccines 11:495-507. http://dx.doi.org/10.1586/erv.12.12
7. Zhang W, Sack DA. 2012. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines 11:677-694. http://dx.doi.org/10.1586/erv.12.37
8. Kansal R, Rasko DA, Sahl JW, Munson GP, Roy K, Luo Q, Sheikh A, Kuhne KJ, Fleckenstein JM. 2013. Transcriptional modulation of enterotoxigenic Escherichia coli virulence genes in response to epithelial cell interactions. Infect Immun 81:259-270. http://dx.doi.org/10.1128/IAI .00919-12
9. Fleckenstein JM, Munson GM, Rasko DA. 2013. Enterotoxigenic Escherichia coli: orchestrated host engagement. Gut Microbes 4:392-396. http://dx.doi.org/10.4161/gmic.25861
10. Fleckenstein J, Sheikh A, Qadri F. 2014. Novel antigens for enterotoxigenic Escherichia coli vaccines. Expert Rev Vaccines 13:631-639. http://dx.doi.org/10.1586/14760584.2014.905745
11. Sheikh A, Luo Q, Roy K, Shabaan S, Kumar P, Qadri F, Fleckenstein JM. 2014. Contribution of the highly conserved EaeH surface protein to enterotoxigenic Escherichia coli pathogenesis. Infect Immun 82:3657-3666. http://dx.doi.org/10.1128/IAI.01890-14
12. Kumar P, Luo Q, Vickers TJ, Sheikh A, Lewis WG, Fleckenstein JM. 2014. EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, degrades intestinal mucin. Infect Immun 82:500-508. http://dx.doi.org/10.1128/IAI.01078-13
13. Luo Q, Kumar P, Vickers TJ, Sheikh A, Lewis WG, Rasko DA, Sistrunk J, Fleckenstein JM. 2014. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect Immun 82:509-521. http://dx.doi.org/10.1128/IAI.01106-13
14. Fleckenstein JM, Roy K, Fischer JF, Burkitt M. 2006. Identification of a two-partner secretion locus of enterotoxigenic Escherichia coli. Infect Immun 74:2245-2258. http://dx.doi.org/10.1128/IAI.74.4.2245-2258.2006
15. Roy K, Hilliard GM, Hamilton DJ, Luo J, Ostmann MM, Fleckenstein JM. 2009. Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells. Nature 457:594-598. http://dx.doi.org/10 .1038/nature07568
16. Fleckenstein JM, Roy K. 2009. Purification of recombinant high molecular weight two-partner secretion proteins from Escherichia coli. Nat Protoc 4:1083-1092. http://dx.doi.org/10.1038/nprot.2009.87
17. Allen KP, Randolph MM, Fleckenstein JM. 2006. Importance of heatlabile enterotoxin in colonization of the adult mouse small intestine by human enterotoxigenic Escherichia coli strains. Infect Immun 74:869-875. http://dx.doi.org/10.1128/IAI.74.2.869-875.2006
18. Bergstrom KS, Kissoon-Singh V, Gibson DL, Ma C, Montero M, Sham HP, Ryz N, Huang T, Velcich A, Finlay BB, Chadee K, Vallance BA. 2010. Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Pathog 6:e1000902. http://dx.doi.org/10.1371/journal.ppat.1000902
19. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. 2008. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A 105:15064-15069. http://dx.doi.org/10.1073/pnas.0803124105
20. Roy K, Hamilton D, Allen KP, Randolph MP, Fleckenstein JM. 2008. The EtpA exoprotein of enterotoxigenic Escherichia coli promotes intestinal colonization and is a protective antigen in an experimental model of murine infection. Infect Immun 76:2106-2112. http://dx.doi.org/10.1128/IAI.01304-07
21. Knutton S, Lloyd DR, Candy DC, McNeish AS. 1984. In vitro adhesion of enterotoxigenic Escherichia coli to human intestinal epithelial cells from mucosal biopsies. Infect Immun 44:514-518
22. Knutton S, McConnell M, Rowe B, McNeish A. 1989. Adhesion and ultrastructural properties of human enterotoxigenic Escherichia coli producing colonization factor antigens III and IV. Infect Immun 57:3364-3371
23. Knutton S, Lloyd DR, Candy DC, McNeish AS. 1985. Adhesion of enterotoxigenic Escherichia coli to human small intestinal enterocytes. Infect Immun 48:824-831
24. Johansson ME, Sjovall H, Hansson GC. 2013. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10:352-361. http://dx.doi.org/10.1038/nrgastro.2013.35
25. Weiss AA, Babyatsky MW, Ogata S, Chen A, Itzkowitz SH. 1996. Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. J Histochem Cytochem 44:1161-1166. http://dx.doi.org/10.1177/44.10.8813081
26. Van Klinken BJ, Tytgat KM, Buller HA, Einerhand AW, Dekker J. 1995. Biosynthesis of intestinal mucins: MUC1, MUC2, MUC3 and more. Biochem Soc Trans 23:814-818. http://dx.doi.org/10.1042/bst0230814
27. Peterson MD, Mooseker MS. 1992. Characterization of the enterocytelike brush border cytoskeleton of the C2BBe clones of the human intestinal cell line, Caco-2. J Cell Sci 102(Pt 3):581-600
28. Bergstrom KS, Xia L. 2013. Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology 23:1026-1037. http://dx.doi.org/10 .1093/glycob/cwt045
29. Larsson JM, Karlsson H, Sjovall H, Hansson GC. 2009. A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. Glycobiology 19:756-766. http://dx.doi .org/10.1093/glycob/cwp048
30. Karlsson NG, Herrmann A, Karlsson H, Johansson ME, Carlstedt I, Hansson GC. 1997. The glycosylation of rat intestinal Muc2 mucin varies between rat strains and the small and large intestine. A study of O-linked oligosaccharides by a mass spectrometric approach. J Biol Chem 272: 27025-27034
31. Rausch P, Steck N, Suwandi A, Seidel JA, Kunzel S, Bhullar K, Basic M, Bleich A, Johnsen JM, Vallance BA, Baines JF, Grassl GA. 2015. Expression of the blood-group-related gene B4galnt2 alters susceptibility to Salmonella infection. PLoS Pathog 11:e1005008. http://dx.doi.org/10 .1371/journal.ppat.1005008
32. Petri WA, Jr, Chapman MD, Snodgrass T, Mann BJ, Broman J, Ravdin JI. 1989. Subunit structure of the galactose and N-acetyl-Dgalactosamine-inhibitable adherence lectin of Entamoeba histolytica. J Biol Chem 264:3007-3012
33. Houpt E, Barroso L, Lockhart L, Wright R, Cramer C, Lyerly D, Petri WA. 2004. Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin. Vaccine 22:611-617. http://dx .doi.org/10.1016/j.vaccine.2003.09.003
34. Johnson AM, Kaushik RS, Francis DH, Fleckenstein JM, Hardwidge PR. 2009. Heat-labile enterotoxin promotes Escherichia coli adherence to intestinal epithelial cells. J Bacteriol 191:178-186. http://dx.doi.org/10 .1128/JB.00822-08
35. Forstner JF, Roomi NW, Fahim RE, Forstner GG. 1981. Cholera toxin stimulates secretion of immunoreactive intestinal mucin. Am J Physiol 240:G10-16
36. Roy K, Hamilton D, Ostmann MM, Fleckenstein JM. 2009. Vaccination with EtpA glycoprotein or flagellin protects against colonization with enterotoxigenic Escherichia coli in a murine model. Vaccine 27:4601-4608. http://dx.doi.org/10.1016/j.vaccine.2009.05.076
37. Luo Q, Vickers TJ, Fleckenstein JM. 2016. Immunogenicity and protective efficacy against ETEC colonization following intradermal, sublingual or oral vaccination with EtpA adhesin. Clin Vaccine Immunol 23:628-637. http://dx.doi.org/10.1128/CVI.00248-16
38. Ermund A, Schutte A, Johansson ME, Gustafsson JK, Hansson GC. 2013. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches. Am J Physiol Gastrointest Liver Physiol 305:G341-G347
39. McGuckin MA, Linden SK, Sutton P, Florin TH. 2011. Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9:265-278. http://dx.doi.org/10 .1038/nrmicro2538
40. Bradbury NA. 2000. Protein kinase-A-mediated secretion of mucin from human colonic epithelial cells. J Cell Physiol 185:408-415. http://dx.doi .org/10.1002/1097-4652(200012)185:3<408::AID-JCP11>3.0.CO;2-2
41. Epple HJ, Kreusel KM, Hanski C, Schulzke JD, Riecken EO, Fromm M. 1997. Differential stimulation of intestinal mucin secretion by cholera toxin and carbachol. Pflugers Arch 433:638-647
42. Gustafsson JK, Ermund A, Ambort D, Johansson ME, Nilsson HE, Thorell K, Hebert H, Sjovall H, Hansson GC. 2012. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 209:1263-1272. http://dx.doi.org/10.1084/jem.20120562
43. Sahl JW, Sistrunk JR, Fraser CM, Hine E, Baby N, Begum Y, Luo Q, Sheikh A, Qadri F, Fleckenstein JM, Rasko DA. 2015. Examination of the enterotoxigenic Escherichia coli population structure during human infection. mBio 6:e00501-15. http://dx.doi.org/10.1128/mBio.00501-15
44. David LA, Weil A, Ryan ET, Calderwood SB, Harris JB, Chowdhury F, Begum Y, Qadri F, LaRocque RC, Turnbaugh PJ. 2015. Gut microbial succession follows acute secretory diarrhea in humans. mBio 6:e00381-15. http://dx.doi.org/10.1128/mBio.00381-15
45. Evans DG, Silver RP, Evans DJ, Jr, Chase DG, Gorbach SL. 1975. Plasmid-controlled colonization factor associated with virulence in Escherichia coli enterotoxigenic for humans. Infect Immun 12:656-667
46. Evans DJ, Jr, Evans DG. 1973. Three characteristics associated with enterotoxigenic Escherichia coli isolated from man. Infect Immun 8:322-328
47. Dorsey FC, Fischer JF, Fleckenstein JM. 2006. Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli. Cell Microbiol 8:1516-1527. http://dx.doi.org/10.1111/j.1462-5822.2006.00736.x
48. Pratt WS, Crawley S, Hicks J, Ho J, Nash M, Kim YS, Gum JR, Swallow DM. 2000. Multiple transcripts of MUC3: evidence for two genes, MUC3A and MUC3B. Biochem Biophys Res Commun 275:916-923. http://dx.doi.org/10.1006/bbrc.2000.3406