Surface properties of Helicobacter pylori urease complex are essential 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 host-pathogen interaction, immune modulation or other actions that underlie H. pylori persistence in its special gastric mucosal niche.
Ondek Pty Ltd and H. pylori Research Laboratory, Microbiology and Immunology, University of Western Australia, Nedlands, Australia.
Tobias D
TD
Schoep
Alma
A
Fulurija
Fayth
F
Good
Wei
W
Lu
Robyn P
RP
Himbeck
Carola
C
Schwan
Sung Sook
SS
Choi
Douglas E
DE
Berg
Peer R E
PR
Mittl
Mohammed
M
Benghezal
Barry J
BJ
Marshall
D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D004795:Enzyme Stability; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics; D054884:Host-Pathogen Interactions; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D013270:Stomach / Q000382:microbiology; D013499:Surface Properties; D014510:Urease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D014510:Urease