The human gastric pathogen Helicobacter pylori expresses several putative outer-membrane proteins (OMPs), but the role of individual OMPs in colonization of the stomach by H. pylori is still poorly understood. The role of four such OMPs (AlpA, AlpB, OipA and HopZ) in a guinea pig model of H. pylori infection has been investigated. Single alpA, alpB, hopZ and oipA isogenic mutants were constructed in the guinea pig-adapted, wild-type H. pylori strain GP15. Guinea pigs were inoculated intragastrically with the wild-type strain, single mutants or a mixture of the wild-type and a single mutant in a 1 : 1 ratio. Three weeks after infection, H. pylori could be isolated from stomach sections of all animals that were infected with the wild-type, the hopZ mutant or the oipA mutant, but from only five of nine (P ¼ 0 . 18) and one of seven (P ¼ 0 . 02) animals that were infected with the alpA or alpB mutants, respectively. The hopZ and oipA mutants colonized the majority of animals that were inoculated with the strain mixture, whereas alpA and alpB mutants could not be isolated from animals that were infected with the strain mixture (P , 0 . 01). Specific IgG antibody responses were observed in all animals that were infected with either the wild-type or a mutant, but IgG levels were lower in animals that were infected with either the alpA or the alpB mutants, compared to the wildtype strain (P , 0 . 05). In conclusion, absence of AlpA or AlpB is a serious disadvantage for colonization of the stomach by H. pylori. INTRODUCTIONThe human pathogen Helicobacter pylori persistently colonizes the gastric mucosa of more than half of the world's population. Colonization by H. pylori always results in active gastritis and is associated with the development of peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma (Kuipers, 1997). Several H. pylori factors are commonly believed to be required for efficient, lifelong colonization of the gastric mucosa, including urease activity (Eaton & Krakowka, 1994), motility by polar sheathed flagella (Eaton et al., 1996) and adherence to gastric epithelial cells (Hessey et al., 1990;Guruge et al., 1998;Yamaoka et al., 2002). Adherence to gastric epithelial cells protects H. pylori against peristalsis and mucosal shedding and warrants access to nutrients that are released from damaged epithelium.It appears that mucosal adhesion of H. pylori is associated directly with mucosal damage (Hessey et al., 1990;Guruge et al., 1998). Adhesion of H. pylori is mediated in part via specific adhesins, such as the sialyl Lewis x -binding protein SabA (Mahdavi et al., 2002) and the Lewis b blood group antigen-binding protein BabA (Boren et al., 1993;Ilver et al., 1998). However, the H. pylori genome also encodes several other outer-membrane proteins (OMPs) that have been associated with adhesion, including OipA, HopZ, AlpA and AlpB (Alm et al., 1999;Evans & Evans, 2000;Tomb et al., 1997). The role of these individual OMPs in adhesion of H. pylori is still relatively poorly un...

Colonization with Helicobacter pylori always results in chronic gastritis, which is controlled by infiltration of mononuclear cells and the subsequent release of cytokines like interleukin (IL)-12. To identify H. pylori factors involved in inducing cytokine production in mononuclear cells, a random H. pylori mutant library was screened for the inability to induce IL-12 production in monocyte THP-1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent twofold decrease in the amount of IL-12 induction compared to the parental strain 1061 (P <0.01). Further characterization of mutant M1 revealed that the kanamycin resistance cassette had integrated in the jhp0945 gene, which is situated in an H. pylori strain-specific plasticity region. Three reference strains possessing this plasticity region induced significantly higher amounts of IL-12 when compared to the H. pylori 26695 reference strain, which does not possess this plasticity region. The role in disease outcome of jhp0945 as well as the neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch population cohort. Firstly, the presence of jhp0947 was completely linked with that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and jhp0949 genes, but not of jhp0945, was significantly associated with duodenal ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947-jhp0949 locus may be a novel putative H. pylori marker for disease outcome independent of the cag PAI.

The off-status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assuming that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system.