Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells
Open accessAbstract
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of death due to diarrheal illness among young children in developing countries, and there is currently no effective vaccine. Many elements of ETEC pathogenesis are still poorly defined. Here we demonstrate that YghJ, a secreted ETEC antigen identified in immunoproteomic studies using convalescent patient sera, is required for efficient access to small intestinal enterocytes and for the optimal delivery of heat-labile toxin (LT). Furthermore, YghJ is a highly conserved metalloprotease that influences intestinal colonization of ETEC by degrading the major mucins in the small intestine, MUC2 and MUC3. Genes encoding YghJ and its cognate type II secretion system (T2SS), which also secretes LT, are highly conserved in ETEC and exist in other enteric pathogens, including other diarrheagenic E. coli and Vibrio cholerae bacteria, suggesting that this mucin-degrading enzyme may represent a shared virulence feature of these important pathogens.
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Cites
Protein structure prediction on the Web: a case study using the Phyre server
Kelley, L. A., & Sternberg, M. J. E. (2009) · Nature Protocols · doi:10.1038/nprot.2009.2 · Cited by 4,154 · see citing works
Kotloff, K. L., Nataro, J. P., Blackwelder, W. C., Nasrin, D., Farag, T. H., Panchalingam, S., Wu, Y., Sow, S. O., Sur, D., Breiman, R. F., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60844-2 · Cited by 3,560 · 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
Using Antibodies: A Laboratory Manual
Harlow, E., & Lane, D. A. (1998) · Cited by 996 · see citing works
Qadri, F., Svennerholm, A., Faruque, S. M., & Sack, R. B. (2005) · Clinical Microbiology Reviews · doi:10.1128/cmr.18.3.465-483.2005 · Cited by 956 · see citing works
Rasko, D. A., Rosovitz, M. J., Myers, G. S. A., Mongodin, E. F., Fricke, W. F., Gajer, P., Crabtree, J., Sebaihia, M., Thomson, N. R., Chaudhuri, R. R., et al. (2008) · Journal of Bacteriology · doi:10.1128/jb.00619-08 · Cited by 881 · see citing works
Self-citationOrigins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany
Rasko, D. A., Webster, D. R., Sahl, J. W., Bashir, A., Boisen, N., Scheutz, F., Paxinos, E. E., Sebra, R., Chin, C.-S., Iliopoulos, D., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106920 · Cited by 825 · see citing works
Self-citation[13] Evolutionary families of metallopeptidases
Rawlings, N. D., & Barrett, A. J. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)48015-3 · Cited by 814 · see citing works
Domain enhanced lookup time accelerated BLAST
Boratyn, G. M., Schäffer, A. A., Agarwala, R., Altschul, S. F., Lipman, D. J., & Madden, T. (2012) · Biology Direct · doi:10.1186/1745-6150-7-12 · Cited by 795 · see citing works
Evans, D. G., Silver, R. P., Evans, D. J., Chase, D. G., & Gorbach, S. L. (1975) · Infection and Immunity · doi:10.1128/iai.12.3.656-667.1975 · Cited by 698 · see citing works
Levine, M., Nalin, D., Hornick, R. B., Bergquist, E. J., Waterman, D., Young, C., Sotman, S. B., & Rowe, B. (1978) · The Lancet · doi:10.1016/s0140-6736(78)90299-4 · Cited by 686 · see citing works
Pathogenesis of Escherichia coli Diarrhea
DuPont, H. L., Formal, S. B., Hornick, R. B., Snyder, M. J., Libonati, J. P., Sheahan, D. G., LaBrec, E. H., & Kalas, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197107012850101 · Cited by 667 · see citing works
Using Antibodies: A Laboratory Manual
Palmer, H. M. (2000) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/45.3.413 · Cited by 653 · 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
Zymography methods for visualizing hydrolytic enzymes
Vandooren, J., Geurts, N., Martens, E., den Steen, P. E. V., & Opdenakker, G. (2013) · Nature Methods · doi:10.1038/nmeth.2371 · Cited by 322 · see citing works
Peterson, K. M., & Mekalanos, J. J. (1988) · Infection and Immunity · doi:10.1128/iai.56.11.2822-2829.1988 · Cited by 316 · see citing works
Molecular mechanisms of enterotoxigenic Escherichia coli infection
Fleckenstein, J. M., Hardwidge, P. R., Munson, G. P., et al. (2009) · Microbes and Infection · doi:10.1016/j.micinf.2009.10.002 · Cited by 316 · see citing works
Self-citationA systematic review of ETEC epidemiology focusing on colonization factor and toxin expression
Isidean, S. D., Riddle, M. S., Savarino, S. J., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.06.084 · Cited by 278 · see citing works
An intestinal mucin is the target substrate for a baculovirus enhancin
Wang, P., & Granados, R. R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6977 · Cited by 275 · see citing works
Moriel, D. G., Bertoldi, I., Spagnuolo, A., Marchi, S., Rosini, R., Nesta, B., Pastorello, I., Corea, V. A. M., Torricelli, G., Cartocci, E., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915077107 · Cited by 261 · see citing works
Levine, M. M., Ristaino, P., Marley, G. M., Smyth, C. J., Knutton, S., Boedeker, E. C., Black, R. E., Young, C., Clements, M. L., & Cheney, C. (1984) · Infection and Immunity · doi:10.1128/iai.44.2.409-420.1984 · Cited by 233 · see citing works
Qadri, F., Saha, A., Ahmed, T., et al. (2007) · Infection and Immunity · doi:10.1128/iai.00459-07 · Cited by 225 · see citing works
Crossman, L. C., Chaudhuri, R. R., Beatson, S. A., Wells, T. J., Desvaux, M., Cunningham, A. F., Petty, N. K., Mahon, V., Brinkley, C., Hobman, J. L., et al. (2010) · Journal of Bacteriology · doi:10.1128/jb.00710-10 · Cited by 185 · 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
Tauschek, M., Gorrell, R. J., Strugnell, R. A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092152899 · Cited by 172 · see citing works
Lepore, L. S., Roelvink, P., & Granados, R. R. (1996) · Journal of Invertebrate Pathology · doi:10.1006/jipa.1996.0070 · Cited by 163 · see citing works
Harrington, S. M., Sheikh, J., Henderson, I. R., Ruiz-Perez, F., Cohen, P. S., & Nataro, J. P. (2009) · Infection and Immunity · doi:10.1128/iai.01494-08 · Cited by 156 · see citing works
Allen, K. P., Randolph, M. M., & Fleckenstein, J. M. (2006) · Infection and Immunity · doi:10.1128/iai.74.2.869-875.2006 · Cited by 143 · see citing works
Self-citationSahl, J. W., Steinsland, H., Redman, J. C., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00932-10 · Cited by 129 · see citing works
Sikora, A. E., Zielke, R. A., Lawrence, D. A., Andrews, P., & Sandkvist, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.211078 · Cited by 125 · 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
Patel, S. K., Dotson, J., Allen, K. P., et al. (2004) · Infection and Immunity · doi:10.1128/iai.72.3.1786-1794.2004 · Cited by 121 · see citing works
Three Characteristics Associated with Enterotoxigenic Escherichia coli Isolated from Man
Evans, D. J., & Evans, D. G. (1973) · Infection and Immunity · doi:10.1128/iai.8.3.322-328.1973 · Cited by 118 · see citing works
Identification of a Two-Partner Secretion Locus of Enterotoxigenic Escherichia coli
Fleckenstein, J. M., Roy, K., Fischer, J. F., & Burkitt, M. J. (2006) · Infection and Immunity · doi:10.1128/iai.74.4.2245-2258.2006 · Cited by 118 · see citing works
Self-citationNakjang, S., Ndeh, D. A., Wipat, A., Bolam, D. N., & Hirt, R. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030287 · Cited by 116 · see citing works
Progress and hurdles in the development of vaccines against enterotoxigenicEscherichia coliin humans
Zhang, W., & Sack, D. A. (2012) · Expert Review of Vaccines · doi:10.1586/erv.12.37 · Cited by 114 · see citing works
Petronzelli, F., Riccio, A., Markham, G. D., Seeholzer, S. H., Genuardi, M., Karbowski, M., Yeung, A. T., Matsumoto, Y., & Bellacosa, A. (2000) · Journal of Cellular Physiology · doi:10.1002/1097-4652(200012)185:3 · Cited by 110 · see citing works
Recent progress toward an enterotoxigenicEscherichia colivaccine
Svennerholm, A., & Lundgren, A. (2012) · Expert Review of Vaccines · doi:10.1586/erv.12.12 · Cited by 110 · see citing works
Kumar, P., Luo, Q., Vickers, T. J., Sheikh, A., Lewis, W. G., & Fleckenstein, J. M. (2013) · Infection and Immunity · doi:10.1128/iai.01078-13 · Cited by 110 · see citing works
Self-citationRuı́z-Pérez, F., Wahid, R., Faherty, C. S., Kolappaswamy, K., Rodriguez, L., Santiago, A. E., Murphy, E., Cross, A. S., Sztein, M. B., & Nataro, J. P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101006108 · Cited by 107 · see citing works
Darsley, M. J., Chakraborty, S., DeNearing, B., et al. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00364-12 · Cited by 104 · see citing works
Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli
Dorsey, F. C., Fischer, J. F., & Fleckenstein, J. M. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00736.x · Cited by 100 · see citing works
Self-citationGenes required for extracellular secretion of enterotoxin are clustered in Vibrio cholerae
Overbye, L. J., Sandkvist, M., & Bagdasarian, M. (1993) · Gene · doi:10.1016/0378-1119(93)90520-d · Cited by 96 · see citing works
Oshima, K., Toh, H., Ogura, Y., Sasamoto, H., Morita, H., Park, S.-H., Ooka, T., Iyoda, S., Taylor, T. D., Hayashi, T., et al. (2008) · DNA Research · doi:10.1093/dnares/dsn026 · Cited by 93 · see citing works
Caco-2 and LS174T cell lines provide different models for studying mucin expression in colon cancer
Bu, X.-D., Li, N., Tian, X., & Huang, P. (2011) · Tissue and Cell · doi:10.1016/j.tice.2011.03.002 · Cited by 92 · see citing works
Lewis, W. G., Robinson, L. S., Perry, J. S. A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.278135 · Cited by 91 · see citing works
Self-citationCohen, P. S., Rossoll, R. M., Cabelli, V. J., et al. (1983) · Infection and Immunity · doi:10.1128/iai.40.1.62-69.1983 · Cited by 88 · see citing works
TagA 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
Parsot, C., Taxman, E., & Mekalanos, J. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.5.1641 · Cited by 85 · see citing works
Comparison of Vibrio cholerae Pathogenicity Islands in Sixth and Seventh Pandemic Strains
Karaolis, D. K. R., Lan, R., Kaper, J. B., et al. (2001) · Infection and Immunity · doi:10.1128/iai.69.3.1947-1952.2001 · Cited by 82 · see citing works
Vejborg, R. M., Friis, C., Hancock, V., Schembri, M. A., & Klemm, P. (2010) · Molecular Genetics and Genomics · doi:10.1007/s00438-010-0532-9 · Cited by 77 · see citing works
Adhesion of a human fecal Escherichia coli strain to mouse colonic mucus
Cohen, P. S., Arruda, J. C., Williams, T. A., et al. (1985) · Infection and Immunity · doi:10.1128/iai.48.1.139-145.1985 · Cited by 75 · see citing works
Enterotoxigenic Escherichia coli Elicits Immune Responses to Multiple Surface Proteins
Roy, K., Bartels, S. R., Qadri, F., & Fleckenstein, J. M. (2010) · Infection and Immunity · doi:10.1128/iai.00264-10 · Cited by 71 · see citing works
Self-citationKansal, R. G., Rasko, D. A., Sahl, J. W., et al. (2012) · Infection and Immunity · doi:10.1128/iai.00919-12 · Cited by 69 · see citing works
Self-citationGutiérrez-Jiménez, J., Arciniega-Martínez, I. M., & Navarro‐García, F. (2008) · Microbial Pathogenesis · doi:10.1016/j.micpath.2008.04.006 · Cited by 55 · see citing works
Mantle, M., & Husar, S. D. (1994) · Infection and Immunity · doi:10.1128/iai.62.4.1219-1227.1994 · Cited by 49 · see citing works
Strozen, T. G., Li, G., & Howard, S. P. (2012) · Infection and Immunity · doi:10.1128/iai.06394-11 · Cited by 47 · see citing works
Adhesin Degradation Accelerates Delivery of Heat-labile Toxin by Enterotoxigenic Escherichia coli
Roy, K., Kansal, R. G., Bartels, S. R., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.251546 · Cited by 44 · see citing works
Harris, J. A., Roy, K., Woo-Rasberry, V., et al. (2011) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0001428 · Cited by 36 · see citing works
Isolation of Large Gel-Forming Mucins
Davies, J. R., & Carlstedt, I. (2000) · Humana Press eBooks · doi:10.1385/1-59259-048-9:003 · Cited by 27 · see citing works
Enterotoxigenic Escherichia coli
Fleckenstein, J. M. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397048-0.00006-1 · Cited by 7 · see citing works
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- Authors
- Luo, Q., Kumar, P., Vickers, T. J., Sheikh, A., Lewis, W. G., Rasko, D. A., Sistrunk, J., & Fleckenstein, J. M.
- Affiliations
- Washington University in St. Louis (US)
- University of Maryland, Baltimore (US)
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2014-02
- Volume
- 82
- Issue
- 2
- Pages
- 509-521
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3911403
- OpenAlex
- W2096305565
- Cited by
- 139
- References
- 62
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 12 · 2023: 10 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 18 · 2018: 14 · 2017: 11 · 2016: 15 · 2015: 12 · 2014: 5 · 2013: 1
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services (HHSN272200900009C)
- U.S. Department of Veterans Affairs (I01 BX001469)
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI89894, HHSN272200900009C, R01AI089894)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK052574)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Vibrio bacteria research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- enterotoxigenic Escherichia coli, metalloproteinases, mucin degradation, MUC2, MUC3, heat-labile toxin, type II secretion system, intestinal colonization, diarrheal disease, Vibrio cholerae
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Epithelial Cells, Escherichia coli Infections, Humans, Hydrolysis, Escherichia coli Proteins, Virulence Factors, Metalloproteases, Mice, Enterotoxigenic Escherichia coli, Mucin-2, Mucin-3
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