Cited by 68Escherichia coli research studiesBiochemical and Structural CharacterizationBacterial Genetics and Biotechnology

SslE Elicits Functional Antibodies That Impair In Vitro Mucinase Activity and In Vivo Colonization by Both Intestinal and Extraintestinal Escherichia coli Strains

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Nesta, Barbara, Valeri, Maria, Spagnuolo, Angela, Rosini, Roberto, Mora, Marirosa, Donato, Paolo, Alteri, Christopher J., Del Vecchio, Mariangela +15 more·2014·PLoS Pathogens

Abstract

SslE, the Secreted and surface-associated lipoprotein from Escherichia coli, has recently been associated to the M60-like extracellular zinc-metalloprotease sub-family which is implicated in glycan recognition and processing. SslE can be divided into two main variants and we recently proposed it as a potential vaccine candidate. By applying a number of in vitro bioassays and comparing wild type, knockout mutant and complemented strains, we have now demonstrated that SslE specifically contributes to degradation of mucin substrates, typically present in the intestine and bladder. Mutation of the zinc metallopeptidase motif of SslE dramatically impaired E. coli mucinase activity, confirming the specificity of the phenotype observed. Moreover, antibodies raised against variant I SslE, cloned from strain IHE3034 (SslEIHE3034), are able to inhibit translocation of E. coli strains expressing different variants through a mucin-based matrix, suggesting that SslE induces cross-reactive functional antibodies that affect the metallopeptidase activity. To test this hypothesis, we used well-established animal models and demonstrated that immunization with SslEIHE3034 significantly reduced gut, kidney and spleen colonization by strains producing variant II SslE and belonging to different pathotypes. Taken together, these data strongly support the importance of SslE in E. coli colonization of mucosal surfaces and reinforce the use of this antigen as a component of a broadly protective vaccine against pathogenic E. coli species.

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Crossref · 10.1371/journal.ppat.1004124

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  • 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”

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Authors
Nesta, B., Valeri, M., Spagnuolo, A., Rosini, R., Mora, M., Donato, P., Alteri, C. J., Del Vecchio, M., Buccato, S., Pezzicoli, A., Bertoldi, I., Buzzigoli, L., Tuscano, G., Falduto, M., Rippa, V., Ashhab, Y., Bensi, G., Fontana, M. R., Seib, K. L., Mobley, H. L. T., Pizza, M., Soriani, M., & Serino, L.
Affiliations
  • Novartis (Italy) (IT)
  • University of Michigan (US)
  • Palestine Polytechnic University (PS)
  • Griffith University (AU)
Corresponding author
Soriani, Marco
Venue
PLoS Pathogens
Published
2014-05-08
Volume
10
Issue
5
Pages
e1004124
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W2039204405
Cited by
68
References
54
Citations by year
2026: 5 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 1
FWCI
4.46
Type
journal article
Language
en
Open access
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Griffith Research Online (submittedVersion)
Funders
  • Imperial College London
  • European Commission (219235)
  • National Institutes of Health (AI43363)
  • National Institute of Allergy and Infectious Diseases (R01AI043363, R01 AI43363)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Escherichia coli, mucinase, zinc metallopeptidase, functional antibodies, mucin degradation, bacterial colonization, vaccine candidate, cross-reactive antibodies, extraintestinal Escherichia coli, intestinal colonization, glycan processing
MeSH terms
Animals, Antibodies, Bacterial, Antibody Formation, Cells, Cultured, Enzyme Activation, Escherichia coli, Escherichia coli Infections, Female, Intestines, Mice, Inbred CBA, Polysaccharide-Lyases, Animals, Outbred Strains, Escherichia coli Proteins, Virulence Factors, Mice, Enteropathogenic Escherichia coli

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