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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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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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