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SslE Elicits Functional Antibodies That Impair Mucinase Activity and Colonization by Both Intestinal and Extraintestinal Strains
Escherichia coli are the predominant facultative anaerobe of the human colonic flora. Although intestinal and extraintestinal pathogenic E. coli are phylogenetically and epidemiologically distinct, we recently proposed a number of protective antigens conserved in most E. coli pathotypes. In this study, we have elucidated the function of the most promising of these antigens, SslE, which is characterized by the presence of a M60-like domain representative of a new extracellular zinc-metalloprotease sub-family. In particular, in vitro analysis of the ability of an sslE knockout mutant strain to transverse an agar-based mucin matrix revealed that SslE is essential to E. coli mucinase activity. Evidence showing that SslE induces functional antibodies, preventing both in vitro mucin degradation but also in vivo gut, kidney and spleen colonization, further support the hypothesis that SslE may facilitate E. coli colonization by favoring the penetration of the sterile inner mucus layer leading to interaction with host cells. Finally, the ability of SslE to also induce protective immunity against sepsis, linked to its presence among different pathotypes, supports the use of such an antigen as a broadly protective E. coli vaccine candidate.
Vyšlo v časopise: SslE Elicits Functional Antibodies That Impair Mucinase Activity and Colonization by Both Intestinal and Extraintestinal Strains. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004124
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004124Souhrn
Escherichia coli are the predominant facultative anaerobe of the human colonic flora. Although intestinal and extraintestinal pathogenic E. coli are phylogenetically and epidemiologically distinct, we recently proposed a number of protective antigens conserved in most E. coli pathotypes. In this study, we have elucidated the function of the most promising of these antigens, SslE, which is characterized by the presence of a M60-like domain representative of a new extracellular zinc-metalloprotease sub-family. In particular, in vitro analysis of the ability of an sslE knockout mutant strain to transverse an agar-based mucin matrix revealed that SslE is essential to E. coli mucinase activity. Evidence showing that SslE induces functional antibodies, preventing both in vitro mucin degradation but also in vivo gut, kidney and spleen colonization, further support the hypothesis that SslE may facilitate E. coli colonization by favoring the penetration of the sterile inner mucus layer leading to interaction with host cells. Finally, the ability of SslE to also induce protective immunity against sepsis, linked to its presence among different pathotypes, supports the use of such an antigen as a broadly protective E. coli vaccine candidate.
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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Combined Systems Approaches Reveal Highly Plastic Responses to Antimicrobial Peptide Challenge inČlánek Two Novel Human Cytomegalovirus NK Cell Evasion Functions Target MICA for Lysosomal Degradation
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