Title Surface properties of Helicobacter pylori urease complex areessential for persistence

The enzymatic activity of Helicobacter pylori’s urease neutralises stomach acidity, thereby promoting infection by this pathogen. Urease protein has also been found to interact with host cells in vitro, although this property’s possible functional importance has not been studied in vivo. To test for a role of the urease surface in the host/pathogen interaction, surface exposed loops that display high thermal mobility were targeted for inframe insertion mutagenesis. H. pylori expressing urease with insertions at four of eight sites tested retained urease activity, which in three cases was at least as stable as was wild-type urease at pH 3. Bacteria expressing one of these four mutant ureases, however, failed to colonise mice for even two weeks, and a second had reduced bacterial titres after longer term (3 to 6 months) colonisation. These results indicate that a discrete surface of the urease complex is important for H. pylori persistence during gastric colonisation. We propose that this surface interacts directly with host components important for the hostpathogen interaction, immune modulation or other actions that underlie H. pylori persistence in its special gastric mucosal niche. Citation: Schoep TD, Fulurija A, Good F, Lu W, Himbeck RP, et al. (2010) Surface Properties of Helicobacter pylori Urease Complex Are Essential for Persistence. PLoS ONE 5(11): e15042. doi:10.1371/journal.pone. 0015042 Editor: Niyaz Ahmed, University of Hyderabad, India Received August 13, 2010; Accepted October 14, 2010; Published November 29, 2010 Copyright: 2010 Schoep 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. Funding: Tobias D. Schoep, Alma Fulurija, Fayth Good, Wei Lu, Robyn P. Himbeck, Carola Schwan, Mohammed Benghezal and Barry J. Marshall are employees of Ondek Pty Ltd and participated in the study design, data collection and analysis, and preparation of the manuscript. Competing Interests: In the name of Ondek, Mohammed Benghezal, Doug E. Berg, Alma Fulurija, Tobias D. Schoep and Barry J. Marshall filed, in June 2010, an Australian Provisional Patent Application No. 2010902818 entitled ’Means Of Controlling Infection Persistence Of Helicobacter Pylori’. Their competing interests are as follows: Tobias D. Schoep: ownership of shares, paid employment, Australian Provisional Patent Application No. 2010902818. Alma Fulurija: ownership of shares, paid employment, Australian Provisional Patent Application No. 2010902818. Fayth Good: paid employment. Wei Lu: ownership of shares, paid employment. Robyn P. Himbeck: ownership of shares, paid employment. Carola Schwan: ownership of shares, paid employment. Douglas E. Berg: ownership of shares, consultant, Australian Provisional Patent Application No. 2010902818. Peer R. E. Mittl: ownership of shares, consultant. Mohammed Benghezal: ownership of shares, paid employment, Australian Provisional Patent Application No. 2010902818 Barry J. Marshall: ownership of shares, Australian Provisional Patent Application No. 2010902818. The authors confirm that the above mentioned conflicts do not alter their adherence to all PLoS ONE policies on sharing data and materials as detailed online in the PLoS One guide for authors. * E-mail: mohammed.benghezal@uwa.edu. au ¤a Current address: Departments of Molecular, Cellular and Developmental Biology and of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California, United States of America ¤b Current address: College of Pharmacy, Sahmyook University, Seoul, South Korea