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

PLoS Pathogens

Yaqoub Ashhab¹  Harry L. T. Mobley²  Christopher J. Alteri²  Kate L. Seib³  Isabella Bertoldi⁴  Maria Valeri⁴  Mariagrazia Pizza⁴  Giuliano Bensi⁴  Maria Falduto⁴  Scilla Buccato⁴  Lapo Buzzigoli⁴  Giovanna Tuscano⁴  Laura Serino⁴  Angela Spagnuolo⁴  Alfredo Pezzicoli⁴  Roberto Rosini⁴  Mariangela Del Vecchio⁴  Barbara Nesta⁴  Valentina Rippa⁴  Marco Soriani⁴  Paolo Donato⁴  Marirosa Mora⁴  Maria Rita Fontana⁴ 

[1] Biotechnology Research Center, Palestine Polytechnic University, Hebron, Palestine;Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America;Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia;Novartis Vaccines and Diagnostics Srl, Siena, Italy

关键词: Mouse models;    Gastrointestinal tract;    Antibodies;    Mucin;    Bacterial pathogens;    Sequence motif analysis;    Enzyme-linked immunoassays;    Vaccines;   

DOI  :  10.1371/journal.ppat.1004124

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY