Pathogenic E. coli exploits SslE mucinase activity to translocate through the mucosal barrier and get access to host cells

PLoS One. 2015 Mar 19;10(3):e0117486. doi: 10.1371/journal.pone.0117486. eCollection 2015.

Abstract

SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as a potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting a human in vitro model of mucus-secreting cells, we demonstrated that bacteria expressing SslE have a metabolic benefit which results in an increased growth rate postulating the importance of this antigen in enhancing E. coli fitness. We also observed that SslE expression facilitates E. coli penetration of the mucus favouring bacteria adhesion to host cells. Moreover, we found that SslE-mediated opening of the mucosae contributed to the activation of pro-inflammatory events. Indeed, intestinal cells infected with SslE-secreting bacteria showed an increased production of IL-8 contributing to neutrophil recruitment. The results presented in this paper conclusively designate SslE as an important colonization factor favouring E. coli access to both metabolic substrates and target cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / enzymology
  • Escherichia coli / pathogenicity*
  • Escherichia coli Proteins / metabolism*
  • Humans
  • Intestinal Mucosa / microbiology*
  • Polysaccharide-Lyases / metabolism*
  • Virulence
  • Virulence Factors / metabolism*

Substances

  • Escherichia coli Proteins
  • SslE protein, E coli
  • Virulence Factors
  • Polysaccharide-Lyases
  • hyaluronate lyase

Grants and funding

This work was mainly supported by internal funding from Novartis Vaccines and Diagnostics. However, it was also partly supported by funding under both the grant PON01_00117 from the Italian “Ministero dell’Istruzione, dell’Università e della Ricerca” and the EMIDA ERA-NET “Coordination of European Research on Emerging and Major Infectious Diseases of Livestock” (financed by the European Commission’s Seventh Framework Programme project no. 219235) as part of the project “Combatting colibacillosis-a genomics-based approach.” The funder provided support in the form of salaries for authors MV, SRP, BN, LS, MGP, MS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The affiliation to the commercial funder of this research study “Novartis Vaccines and Diagnostics S.r.l.” does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.