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The Pic Protease of Enteroaggregative Escherichia coli Promotes Intestinal Colonization and Growth in the Presence of Mucin
Open accessAbstract
Enteroaggregative Escherichia coli (EAEC) is increasingly being recognized as a cause of diarrheal disease in diverse populations. No small animal model is currently available to study this pathogen. We report here that conventional mice orally inoculated with prototype EAEC strain 042 generally became colonized, though the abundance of organisms cultured from their stool varied substantially among individual animals. In contrast, mice whose water contained 5 g/liter streptomycin consistently became colonized at high levels (ca. 10 8 CFU/g of stool). Neither conventional nor streptomycin-treated mice developed clinical signs or histopathologic abnormalities. Using specific mutants in competition with the wild-type strain, we evaluated the contribution of several putative EAEC virulence factors to colonization of streptomycin-treated mice. Our data suggest that the dispersin surface protein and Pic, a serine protease autotransporter secreted by EAEC and Shigella flexneri , promote colonization of the mouse. In contrast, we found no role for the aggregative adherence fimbriae, the transcriptional activator AggR, or the surface factor termed Air (entero a ggregative i mmunoglobulin r epeat protein). To study Pic further, we constructed a single nucleotide mutation in strain 042 which altered only the Pic catalytic serine (strain 042PicS258A). Fractionation of the tissue at 24 h and 3 days demonstrated an approximate 3-log 10 difference between 042 and 042PicS258A in the lumen and mucus layer and adherent to tissue. Strains 042 and 042PicS258A adhered similarly to mouse tissue ex vivo. While no growth differences were observed in a continuous-flow anaerobic intestinal simulator system, the wild-type strain exhibited a growth advantage over 042PicS258A in a culture of cecal mucus and in cecal contents in vitro; this difference was manifest only after 6 h of growth. Moreover, enhanced growth of the wild type was observed in comparison with that of the mutant in minimal medium containing mucin but not in the absence of mucin. The data suggest a novel metabolic role for the Pic mucinase in EAEC colonization.
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“Proteases from different infectious agents such as Pic in diarrheagenic E. coli and Shigella, or vibriolysin in V. cholera, degrade the colonic mucus, which is a key step facilitating epithelium invasion.10,68,69,71”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [71]
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“the serine protease Pic produced by E. coli (EAEC), Citrobacter and Shigella flexneri is a virulence factor associated with adherence, colonization and evasion of the innate immune system.68–71”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [71]
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Cites
Donnenberg, M. S., & Kaper, J. B. (1991) · Infection and Immunity · doi:10.1128/iai.59.12.4310-4317.1991 · Cited by 1,051
Carbon nutrition of Escherichia coli in the mouse intestine
Chang, D., Smalley, D. J., Tucker, D. L., Leatham, M. P., Norris, W. E., Stevenson, S. J., Anderson, A. B., Grissom, J. E., Laux, D. C., Cohen, P. S., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307888101 · Cited by 513
Self-citationVirulence Functions of Autotransporter Proteins
Henderson, I. R., & Nataro, J. P. (2001) · Infection and Immunity · doi:10.1128/iai.69.3.1231-1243.2001 · Cited by 448
Self-citationAsmar, R. E., Panigrahi, P., Bamford, P. D., Berti, I., Not, T., Coppa, G. V., Catassi, C., & Fasano, A. (2002) · Gastroenterology · doi:10.1053/gast.2002.36578 · Cited by 369
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
Self-citationHeterogeneity of Enteroaggregative Escherichia Coli Virulence Demonstrated
Nataro, J. P., Yikang, D., Cookson, S., Cravioto, A., Savarino, S. J., Guers, L., Levine, M. M., & Tacket, C. O. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/171.2.465 · Cited by 326
Self-citationBhan, M. K., Raj, P., Levine, M. M., Kaper, J. B., Bhandari, N., Srivastava, R., Kumar, R., & Sazawal, S. (1989) · The Journal of Infectious Diseases · doi:10.1093/infdis/159.6.1061 · Cited by 323
Nataro, J. P., Deng, Y., Maneval, D. R., German, A. L., Martin, W. C., & Levine, M. M. (1992) · Infection and Immunity · doi:10.1128/iai.60.6.2297-2304.1992 · Cited by 303
Self-citationCzeczulin, J. R., Balepur, S., Hicks, S., Phillips, A. D., HALL, R. H., Kothary, M. H., Navarro‐García, F., & Nataro, J. P. (1997) · Infection and Immunity · doi:10.1128/iai.65.10.4135-4145.1997 · Cited by 279
Self-citationA novel dispersin protein in enteroaggregative Escherichia coli
Sheikh, J., Czeczulin, J. R., Harrington, S. M., Hicks, S., Henderson, I. R., Bouguénec, C. L., Gounon, P., Phillips, A. D., & Nataro, J. P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16172 · Cited by 255
Self-citationSavarino, S. J., Fasano, A., Robertson, D. C., & Levine, M. M. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115151 · Cited by 245
Roles for Fis and YafK in biofilm formation by enteroaggregative Escherichia coli
Sheikh, J., Hicks, S., DallʼAgnol, M., Phillips, A. D., & Nataro, J. P. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02512.x · Cited by 231
Self-citationItoh, Y., NAGANO, I., Kunishima, M., & Ezaki, T. (1997) · Journal of Clinical Microbiology · doi:10.1128/jcm.35.10.2546-2550.1997 · Cited by 220
Nataro, J. P., Yikang, D., Yingkang, D., & Walker, K. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.15.4691-4699.1994 · Cited by 216
Self-citationAdachi, J. A., Jiang, Z., Mathewson, J. J., Verenkar, M. P., Thompson, S., Martinez‐Sandoval, F., Steffen, R. J., Ericsson, C. D., & DuPont, H. L. (2001) · Clinical Infectious Diseases · doi:10.1086/320756 · Cited by 215
Levine, M. M., Catterina Ferreccio, R., Prado, V., Marisol Cayazzo, C., Abrego, P. L., Martinez, J., Leonardo Maggi, C., Baldini, M. M., Martin, W., Maneval, D. R., et al. (1993) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a116788 · Cited by 190
Self-citationBenjelloun‐Touimi, Z., Sansonetti, P. J., & Parsot, C. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.mmi_17010123.x · Cited by 189
Functional Comparison of Serine Protease Autotransporters of Enterobacteriaceae
Dutta, P. R., Cappello, R. E., Navarro‐García, F., & Nataro, J. P. (2002) · Infection and Immunity · doi:10.1128/iai.70.12.7105-7113.2002 · Cited by 182
Self-citationJav, S., Nishi, J., Wakimoto, N., Erdene, S., Nataro, J. P., Sheikh, J., Iwashita, M., Manago, K., Tokuda, K., Yoshinaga, M., et al. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.1.133-139.2004 · Cited by 159
Self-citationGuyer, D. M., Kao, J.-S., & Mobley, H. L. T. (1998) · Infection and Immunity · doi:10.1128/iai.66.9.4411-4417.1998 · Cited by 158
Rajakumar, K., Sasakawa, C., & Adler, B. (1997) · Infection and Immunity · doi:10.1128/iai.65.11.4606-4614.1997 · Cited by 154
Fasano, A., Noriega, F. R., Maneval, D. R., Chanasongcram, S., Russell, R. G., Guandalini, S., & Levine, M. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117991 · Cited by 149
Characterization of a Hemoglobin Protease Secreted by the Pathogenic Escherichia coli Strain EB1
Otto, B. R., van Dooren, S. J. M., Nuijens, J. H., Luirink, J., & Oudega, B. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.6.1091 · Cited by 139
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
Miranda, R. L., Conway, T., Leatham, M. P., Chang, D., Norris, W. E., Allen, J. H., Stevenson, S. J., Laux, D. C., & Cohen, P. S. (2004) · Infection and Immunity · doi:10.1128/iai.72.3.1666-1676.2004 · Cited by 133
Self-citationWadolkowski, E. A., Laux, D. C., & Cohen, P. S. (1988) · Infection and Immunity · doi:10.1128/iai.56.5.1030-1035.1988 · Cited by 132
Self-citationEnteroaggregative Escherichia coli Is a Cause of Acute Diarrheal Illness: A Meta-Analysis
Huang, D. B., Nataro, J. P., DuPont, H. L., Kamat, P. P., Mhatre, A. D., Okhuysen, P. C., & Chiang, T. (2006) · Clinical Infectious Diseases · doi:10.1086/505869 · Cited by 128
Self-citationGermani, Y., Minssart, P., Vohito, M., Yassibanda, S., Glaziou, P., Hocquet, D., Berthélémy, P., & Morvan, J. M. (1998) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1998.59.1008 · Cited by 111
Heimer, S. R., Rasko, D. A., Lockatell, C. V., Johnson, D. E., & Mobley, H. L. T. (2003) · Infection and Immunity · doi:10.1128/iai.72.1.593-597.2004 · Cited by 110
Enteroaggregative Escherichia coli and Salmonella associated with nondysenteric persistent diarrhea
Bhan, M. K., Khoshoo, V., Sommerfelt, H., Raj, P., Sazawal, S., & Srivastava, R. (1989) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-198908000-00005 · Cited by 105
Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human intestinal mucosa
Knutton, S., Shaw, R. K., Bhan, M. K., Smith, H. R., McConnell, M. M., Cheasty, T., WILLIAMS, P. H., & Baldwin, T. J. (1992) · Infection and Immunity · doi:10.1128/iai.60.5.2083-2091.1992 · Cited by 102
Sweeney, N. J., Laux, D. C., & Cohen, P. S. (1996) · Infection and Immunity · doi:10.1128/iai.64.9.3504-3511.1996 · Cited by 98
Self-citationPicU, a second serine protease autotransporter of uropathogenic Escherichia coli
Parham, N. J., Srinivasan, U., Desvaux, M., Foxman, B., Marrs, C. F., & Henderson, I. R. (2003) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(03)00862-0 · Cited by 97
Self-citationMøller, A. K., Leatham, M. P., Conway, T., Nuijten, P. J. M., Haan, L. A. M., Krogfelt, K. A., & Cohen, P. S. (2003) · Infection and Immunity · doi:10.1128/iai.71.4.2142-2152.2003 · Cited by 95
Self-citationTolner, B., Ubbink-Kok, T., Poolmann, B., & Konings, W. N. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.mmi_18010123.x · Cited by 91
Stathopoulos, C., Provence, D. L., & Curtiss, R. (1999) · Infection and Immunity · doi:10.1128/iai.67.2.772-781.1999 · Cited by 91
Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo.
Fasano, A., Noriega, F. R., Liao, F. M., Wang, W., & Levine, M. M. (1997) · Gut · doi:10.1136/gut.40.4.505 · Cited by 91
Piva, I. C., Pereira, A. L., Ferraz, L. R., Silva, R. S. N., Vieira, A. C., Blanco, J. E., Blanco, M., Blanco, J., & Giugliano, L. G. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.5.1827-1832.2003 · Cited by 89
Leyton, D. L., Sloan, J., Hill, R., Doughty, S., & Hartland, E. L. (2003) · Infection and Immunity · doi:10.1128/iai.71.11.6307-6319.2003 · Cited by 86
Stecher, B., Paesold, G., Barthel, M., Kremer, M., Jantsch, J., Stallmach, T., Heikenwälder, M. F., & Hardt, W. (2006) · Infection and Immunity · doi:10.1128/iai.00072-06 · Cited by 74
Benítez, J. A., Spelbrink, R. G., Silva, A. J., Phillips, T. E., Stanley, C. M., Boesman-Finkelstein, M., & Finkelstein, R. A. (1997) · Infection and Immunity · doi:10.1128/iai.65.8.3474-3477.1997 · Cited by 68
Plasmid-Encoded Toxin of Enteroaggregative Escherichia coli is Internalized by Epithelial Cells
Navarro‐García, F., Canizalez‐Román, A., Luna, J., Sears, C. L., & Nataro, J. P. (2001) · Infection and Immunity · doi:10.1128/iai.69.2.1053-1060.2001 · Cited by 66
Self-citationNevola, J. J., Laux, D. C., & Cohen, P. S. (1987) · Infection and Immunity · doi:10.1128/iai.55.12.2884-2890.1987 · Cited by 61
Self-citationEilA, a HilA‐like regulator in enteroaggregative Escherichia coli
Sheikh, J., Dudley, E. G., Sui, B., Tamboura, B., Suleman, A., & Nataro, J. P. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05234.x · Cited by 55
Self-citationMcCormick, B. A., Klemm, P., Krogfelt, K. A., Burghoff, R. L., Pallesen, L., Laux, D. C., & Cohen, P. S. (1993) · Microbial Pathogenesis · doi:10.1006/mpat.1993.1004 · Cited by 40
Self-citationUse of a Continuous-Flow Anaerobic Culture To Characterize Enteric Virulence Gene Expression
Ruı́z-Pérez, F., Sheikh, J., Davis, S., Boedeker, E. C., & Nataro, J. P. (2004) · Infection and Immunity · doi:10.1128/iai.72.7.3793-3802.2004 · Cited by 28
Self-citationDetection of Tsh protein mucinolytic activity by SDS-PAGE
Kobayashi, R. K. T., Gaziri, L. C. J., Venâncio, E. J., & Vidotto, M. C. (2006) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2006.10.002 · Cited by 8
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Cornick, S., Tawiah, A., & Chadee, K. (2015) · Tissue Barriers · doi:10.4161/21688370.2014.982426 · Cited by 556
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Metadata
- Authors
- Harrington, S. M., Sheikh, J., Henderson, I. R., Ruiz-Perez, F., Cohen, P. S., & Nataro, J. P.
- Affiliations
- Center for Vaccine Development, University of Maryland School of Medicine, and Departments of Microbiology and Immunology
- University of Maryland, Baltimore (US)
- University of Rhode Island (US)
- Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2009-06
- Volume
- 77
- Issue
- 6
- Pages
- 2465-2473
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC2687332
- OpenAlex
- W2161414686
- Cited by
- 156
- References
- 47
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 13 · 2019: 6 · 2018: 12 · 2017: 10 · 2016: 6 · 2015: 10 · 2014: 11 · 2013: 16 · 2012: 11
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Journal of Media Literacy Education (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R56AI048945, R01AI033096, R01AI043615, R01AI048945, AI33096, AI43615, AI48945, AI03615, R56AI043615)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Life Sciences › Immunology and Microbiology › Microbiology › Enterobacteriaceae and Cronobacter Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- enteroaggregative Escherichia coli, mucinase, intestinal colonization, mucin, aggregative adherence fimbriae, aggR, virulence factors, diarrheal disease
- MeSH terms
- Animals, Cecum, Child, Escherichia coli, Feces, Female, Humans, Intestinal Mucosa, Mice, Inbred BALB C, Mucins, Polysaccharide-Lyases, Serine Endopeptidases, Shigella flexneri, Virulence, Colony Count, Microbial, Mutagenesis, Site-Directed, Gene Deletion, Amino Acid Substitution, Catalytic Domain, Escherichia coli Proteins, Virulence Factors, Mice
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