Role of the Helicobacter pylori outer-membrane proteins AlpA and AlpB in colonization of the guinea pig stomach

Abstract

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...

Helicobacter pylori AlpA and AlpB Bind Host Laminin and Influence Gastric Inflammation in Gerbils

“…Previous studies clearly indicate a role for the alpAB locus in mediating adherence in vitro; however, in vivo studies examining the role of the alpAB locus in colonization and pathogenesis have been limited. Reduced numbers of colonized animals have been noted in guinea pigs inoculated with H. pylori strain GP15 alpA and alpB mutants (13). Abrogation of alpAB in strain TN renders the bacteria unable to colonize mice while the same mutation in a 43505 strain background reduces colonization density (31).…”

Pathogenesis ofHelicobacter pyloriInfection

“…Furthermore, rodent-adapted H. pylori strains are still required. Therefore, the use of the guinea pig model has been limited to testing the effects of H. pylori immunization and vaccination (140,309,528), vitamin supplementation (572), and the mutation of adhesins of H. pylori (114).…”

Oral Immunization with Recombinant Mycobacterium smegmatis Expressing the Outer Membrane Protein 26-Kilodalton Antigen Confers Prophylactic Protection against Helicobacter pylori Infection

“…H. pylori strains express a large set of Omps (21), whose role is still not completely understood. Several lines of evidence suggest that some Omps are essential for H. pylori colonization in the stomach (5,32). Thus, these cell surface-expressed proteins are logical candidates for vaccine development.…”