Abstract
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.