Prediction of extracellular proteases of the human pathogen Helicobacter pylori reveals proteolytic activity of the Hp1018/19 protein HtrA

  • Exported proteases of Helicobacter pylori (H. pylori) are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI). Among these, we found the predicted serine protease HtrA (Hp1019), which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.

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Author:Martin LöwerGND, Christiane Weydig, Dirk MetzlerORCiDGND, Andreas Reuter, Anna Starzinski-PowitzORCiDGND, Silja WeßlerORCiDGND, Gisbert SchneiderORCiDGND
Pubmed Id:
Parent Title (English):PLoS One
Publisher:Public Library of Science
Place of publication:Lawrence, Kan.
Document Type:Article
Date of Publication (online):2008/08/23
Date of first Publication:2008/08/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2008/11/12
Page Number:8
First Page:1
Last Page:8
Copyright Löwer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Biowissenschaften / Biowissenschaften
Informatik und Mathematik / Informatik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0