The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo
Open accessAbstract
Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen and tightly adheres to human colonic epithelium by forming attaching/effacing lesions. To reach the epithelial surface, EHEC must penetrate the thick mucus layer protecting the colonic epithelium. In this study, we investigated how EHEC interacts with the intestinal mucus layer using mucin-producing LS174T colon carcinoma cells and human colonic mucosal biopsies. The level of EHEC binding and attaching/effacing lesion formation in LS174T cells was higher compared to mucin-deficient colon carcinoma cell lines, and initial adherence was independent of the presence of flagellin, Escherichia coli common pilus, or long polar fimbriae. Although EHEC infection did not affect gene expression of secreted mucins, it resulted in reduced MUC2 glycoprotein levels. This effect was dependent on the catalytic activity of the secreted metalloprotease StcE, which reduced the inner mucus layer and thereby promoted EHEC access and binding to the epithelium in vitro and ex vivo. Given the lack of efficient therapies against EHEC infection, StcE may represent a suitable target for future treatment and prevention strategies.
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StcE and SslE, metalloproteases from diarrheagenic E. coli strains, cleave mucin glycoproteins, which may help the pathogen to reach the epithelium.
“StcE and SslE, metalloproteases from diarrheagenic E. coli strains, also cleave mucin glycoproteins, which may help the pathogen to reach the epithelium.74–76”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [74]
The zinc metalloproteases StcE and SslE secreted by E. coli EHEC and EPEC/ETEC respectively contribute to intimate adherence of these bacteria to host cells, a process essential for colonization.
“Finally, the zinc metalloproteases StcE and SslE secreted by E. coli EHEC and EPEC/ETEC respectively, contribute to intimate adherence of these bacteria to host cells, a process that is essential for colonization.73–78”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [74]
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Cites
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
Datsenko, K., & Wanner, B. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.120163297 · Cited by 15,902 · see citing works
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
Johansson, M. E. V., Phillipson, M., Petersson, J., Velcich, A., Holm, L., & Hansson, G. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803124105 · Cited by 2,200 · see citing works
Recent Advances in Understanding Enteric Pathogenic Escherichia coli
Croxen, M. A., Law, R. J., Scholz, R., Keeney, K. M., Wlodarska, M., & Finlay, B. B. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00022-13 · Cited by 1,578 · see citing works
Mucin dynamics and enteric pathogens
McGuckin, M. A., Lindén, S. K., Sutton, P., & Florin, T. H. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2538 · Cited by 1,428 · see citing works
Johansson, M. E. V., Gustafsson, J. K., Holmén-Larsson, J., Jabbar, K. S., Xia, L., Xu, H., Ghishan, F. K., Carvalho, F. A., Gewirtz, A. T., Sjövall, H., et al. (2014) · Gut · doi:10.1136/gutjnl-2012-303207 · Cited by 1,004 · see citing works
Bergstrom, K. S. B., Kissoon-Singh, V., Gibson, D. L., Ma, C., Montero, M., Sham, H. P., Ryz, N., Huang, T., Velcich, A., Finlay, B. B., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000902 · Cited by 625 · see citing works
Henderson, I. R., Czeczulin, J., Eslava, C., Noriega, F., & Nataro, J. P. (1999) · Infection and Immunity · doi:10.1128/iai.67.11.5587-5596.1999 · Cited by 357 · see citing works
Gould, L. H., Mody, R. K., Ong, S. K., Clogher, P., Cronquist, A., Garman, K. N., Lathrop, S. L., Medus, C., Spina, N., Webb, T. H., et al. (2013) · Foodborne Pathogens and Disease · doi:10.1089/fpd.2012.1401 · Cited by 341 · see citing works
Vertical agarose gel electrophoresis and electroblotting of high‐molecular‐weight proteins
Warren, C. M., Krzesiński, P., & Greaser, M. L. (2003) · Electrophoresis · doi:10.1002/elps.200305392 · Cited by 307 · see citing works
Rendón, M. A., Saldaña‐Ahuactzi, Z., Erdem, A. L., Monteiro‐Neto, V., Vázquez, A., Kaper, J. B., Puente, J. L., & Girón, J. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704104104 · Cited by 305 · see citing works
Microbial adhesins to gastrointestinal mucus
Juge, N. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.10.001 · Cited by 304 · see citing works
Self-citationFreedman, S. B., Xie, J., Neufeld, M. S., Hamilton, W. L., Hartling, L., & Tarr, P. I. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw099 · Cited by 267 · see citing works
Gagnon, M., Zihler, A., Chervet, N., Chassard, C., & Lacroix, C. (2013) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2013.06.027 · Cited by 244 · see citing works
In, J., Foulke-Abel, J., Zachos, N. C., Hansen, A.-M., Kaper, J. B., Bernstein, H. D., Halushka, M., Blutt, S., Estes, M. K., Donowitz, M., et al. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.10.001 · Cited by 239 · see citing works
Mucin Dynamics in Intestinal Bacterial Infection
Lindén, S. K., Florin, T. H., & McGuckin, M. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003952 · Cited by 235 · see citing works
Tzipori, S. R., Karch, H., Wachsmuth, K., Robins-Browne, R. M., O’Brien, A. D., Lior, H., Cohen, M. L., Smithers, J., & Levine, M. M. (1987) · Infection and Immunity · doi:10.1128/iai.55.12.3117-3125.1987 · Cited by 218 · see citing works
Renal and neurological involvement in typical Shiga toxin-associated HUS
Trachtman, H., Austin, C., von Lewinski, M., et al. (2012) · Nature Reviews Nephrology · doi:10.1038/nrneph.2012.196 · Cited by 217 · see citing works
Bacterial Flagella: Twist and Stick, or Dodge across the Kingdoms
Rossez, Y., Wolfson, E. B., Holmes, A., Gally, D. L., & Holden, N. J. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004483 · Cited by 214 · see citing works
Lathem, W. W., Grys, T. E., Witowski, S. E., Torres, A. G., Kaper, J. B., Tarr, P. I., & Welch, R. A. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02997.x · Cited by 183 · see citing works
Erdem, A. L., Avelino, F., Xicohtencatl‐Cortés, J., & Girón, J. A. (2007) · Journal of Bacteriology · doi:10.1128/jb.00464-07 · Cited by 174 · see citing works
Navabi, N., McGuckin, M. A., & Lindén, S. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068761 · Cited by 157 · see citing works
Haemagglutinin/protease expression and mucin gel penetration in El Tor biotype Vibrio cholerae
Silva, A. J., Pham, K., & Benítez, J. A. (2003) · Microbiology · doi:10.1099/mic.0.26086-0 · Cited by 150 · see citing works
Bergstrom, K., Guttman, J. A., Rumi, M. A. K., Ma, C., Bouzari, S., Khan, M. A., Gibson, D. L., Vogl, A. W., & Vallance, B. A. (2007) · Infection and Immunity · doi:10.1128/iai.00093-07 · Cited by 145 · see citing works
Grys, T. E., Siegel, M. B., Lathem, W. W., & Welch, R. A. (2005) · Infection and Immunity · doi:10.1128/iai.73.3.1295-1303.2005 · Cited by 138 · see citing works
Enterohemorrhagic Escherichia coli Adhesins
McWilliams, B. D., & Torres, A. G. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.ehec-0003-2013 · Cited by 131 · see citing works
Fitzhenry, R., Pickard, D., Hartland, E. L., Reece, S., Gordon Dougan, B., Phillips, A. D., & Frankel, G. M. (2002) · Gut · doi:10.1136/gut.50.2.180 · Cited by 126 · see citing works
van Klinken, B. J., Oussoren, E., Weenink, J., Strous, G. J., Büller, H. A., Dekker, J. P., & Einerhand, A. W. C. (1996) · Glycoconjugate Journal · doi:10.1007/bf00702340 · Cited by 123 · see citing works
Stevens, M. P., & Frankel, G. M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.ehec-0007-2013 · Cited by 120 · see citing works
Guo, W., Lonardo, F., Ueda, T., Kim, T. K., Huvos, A. G., Healey, J. H., & Ladanyi, M. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990118)80:2 · Cited by 120 · see citing works
Cross Talk between Type III Secretion and Flagellar Assembly Systems in Pseudomonas aeruginosa
Soscia, C., Hachani, A., Bernadac, A., et al. (2007) · Journal of Bacteriology · doi:10.1128/jb.01677-06 · Cited by 96 · see citing works
Huet, G., Kim, I., de Bolós, C., et al. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.3.1275 · Cited by 93 · see citing works
Walsham, A. D. S., MacKenzie, D. A., Cook, V., Wemyss-Holden, S. A., Hews, C. L., Juge, N., & Schüller, S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00244 · Cited by 89 · see citing works
Self-citationTagA is a secreted protease of Vibrio cholerae that specifically cleaves mucin glycoproteins
Szabady, R. L., Yanta, J. H., Halladin, D. K., Schofield, M. J., & Welch, R. A. (2010) · Microbiology · doi:10.1099/mic.0.044529-0 · Cited by 87 · see citing works
Genetic Diversity among Clonal Lineages withinEscherichia coliO157:H7 Stepwise Evolutionary Model
Feng, P., Monday, S. R., Lacher, D. W., et al. (2007) · Emerging infectious diseases · doi:10.3201/eid1311.070381 · Cited by 84 · see citing works
Yu, A. C. Y., Worrall, L. J., & Strynadka, N. C. J. (2012) · Structure · doi:10.1016/j.str.2012.02.015 · Cited by 83 · see citing works
Nesta, B., Valeri, M., Spagnuolo, A., Rosini, R., Mora, M., Donato, P., Alteri, C. J., Del Vecchio, M., Buccato, S., Pezzicoli, A., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004124 · Cited by 68 · see citing works
Long polar fimbriae and tissue tropism in Escherichia coli O157:H7
Fitzhenry, R. J., Dahan, S., Torres, A. G., et al. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2006.02.012 · Cited by 65 · see citing works
Gustafsson, J. K., Navabi, N., Rodríguez-Piñeiro, A. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084430 · Cited by 65 · see citing works
Enterohemorrhagic Escherichia coli Colonization of Human Colonic Epithelium In Vitro and Ex Vivo
Lewis, S. B., Cook, V., Tighe, R., & Schüller, S. (2014) · Infection and Immunity · doi:10.1128/iai.02928-14 · Cited by 65 · see citing works
Self-citationValeri, M., Paccani, S. R., Kasendra, M. J., Nesta, B., Serino, L., Pizza, M., & Soriani, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117486 · Cited by 60 · see citing works
Chong, Y., Fitzhenry, R. J., Heuschkel, R. B., et al. (2007) · Microbiology · doi:10.1099/mic.0.2006/003178-0 · Cited by 57 · see citing works
Modulation of Neutrophil Function by a Secreted Mucinase of Escherichia coli O157∶H7
Szabady, R. L., Lokuta, M. A., Walters, K., Anna Huttenlocher, A., & Welch, R. A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000320 · Cited by 54 · see citing works
Characterization of the StcE Protease Activity of <i>Escherichia coli</i> O157:H7
Grys, T. E., Walters, L. L., & Welch, R. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.01806-05 · Cited by 51 · see citing works
Xue, Y., Zhang, H., Wang, H., et al. (2014) · Infection and Immunity · doi:10.1128/iai.01589-13 · Cited by 47 · see citing works
Vieira, M. A. M., Gomes, T. A. T., Ferreira, A. J. P., Knöbl, T., Servin, A. L., & Moal, V. L.-L. (2010) · Infection and Immunity · doi:10.1128/iai.01115-09 · Cited by 43 · see citing works
Animal Models of EnterohemorrhagicEscherichia coliInfection
Ritchie, J. M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.ehec-0022-2013 · Cited by 39 · see citing works
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Martens, E. C., Neumann, M., & Desai, M. S. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0036-x · Cited by 711 · see citing works
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Ducarmon, Q. R., Zwittink, R. D., Hornung, B. V. H., van Schaik, W., Young, V. B., & Kuijper, E. J. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-19 · Cited by 566 · see citing works
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- Authors
- Hews, C. L., Tran, S.-L., Wegmann, U., Brett, B., Walsham, A. D. S., Kavanaugh, D., Ward, N. J., Juge, N., & Schüller, S.
- Affiliations
- University of East Anglia (GB)
- Quadram Institute (GB)
- Norfolk and Norwich University Hospital (GB)
- Corresponding author
- Schüller, Stephanie
- ORCID
- Venue
- Cellular Microbiology
- Publisher
- Wiley
- Published
- 2017-02-15
- Volume
- 19
- Issue
- 6
- Pages
- e12717
- ISSN
- 1462-5814 (ISSN-L)
- PMC
- PMC5434857
- OpenAlex
- W2570203452
- Cited by
- 77
- References
- 46
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 16 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 2
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cellular Microbiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Medical Research Council (MR/J002062/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
- Keywords
- enterohemorrhagic Escherichia coli, metalloproteinases, mucus layer, MUC2, mucin, attaching and effacing lesions, bacterial adhesion, colonic epithelium, LS174T cells, secreted mucins, flagellin, host-pathogen interaction, therapeutic target
- MeSH terms
- Bacterial Adhesion, Cell Line, Colon, Escherichia coli Infections, Flagellin, Humans, Intestinal Mucosa, Metalloendopeptidases, Mucus, Fimbriae, Bacterial, Caco-2 Cells, HT29 Cells, Escherichia coli O157, Escherichia coli Proteins, Mucin-2
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