title: SslE elicits functional antibodies that impair in vitro mucinase activity and in vivo colonization by both intestinal and extraintestinal Escherichia coli strains.
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.
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nesta
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Valeri
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Spagnuolo
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosini
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Marirosa
authors.initials: M
authors.lastname: Mora
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Donato
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Alteri
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Del Vecchio
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Scilla
authors.initials: S
authors.lastname: Buccato
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pezzicoli
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bertoldi
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Lapo
authors.initials: L
authors.lastname: Buzzigoli
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tuscano
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Falduto
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rippa
authors.affiliation: Biotechnology Research Center, Palestine Polytechnic University, Hebron, Palestine.
authors.forename: Yaqoub
authors.initials: Y
authors.lastname: Ashhab
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Fontana
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Seib
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Soriani
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Serino
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D000907:Antibodies, Bacterial / Q000378:metabolism / Q000494:pharmacology*; D000917:Antibody Formation; D002478:Cells, Cultured; D054308:Enteropathogenic Escherichia coli / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007422:Intestines / Q000382:microbiology; D051379:Mice; D008808:Mice, Inbred CBA; D011133:Polysaccharide-Lyases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D029968:Escherichia coli Proteins; C583861:SslE protein, E coli; D037521:Virulence Factors; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase