Abstract. An epizootic of subclinical lymphoplasmacytic gastritis occurred in cynomolgus monkeys maintained at our research facility. Gastric pathology data and histologic sections of 63 adolescent monkeys (2.5-3.5 years old) sacrificed during the epizootic were reviewed. Localized to multifocal reddening of the gastric mucosa was noted grossly in 7 of 44 (16%) monkeys harboring Helicobacter pylori, but not in any of 19 monkeys in which these bacteria were not seen. Gastritis, characterized by accentuation of lymphoplasmacytic infiltrates in antral and to a lesser degree cardiac mucosa, occurred in 42 of 63 (67%) monkeys evaluated and in 42 of 44 (93%) monkeys in which H. pylori was observed microscopically. Two monkeys with H. pylori infection had infiltrate scores that overlapped with the upper limit of scores of H. pylori-negative animals. Coincident with accentuated infiltrates were gastric gland epithelial hyperplasia, reduction in mucin content of surface and gland epithelia, and comparatively minor infiltrates of neutrophils in superficial lamina propria and gastric glands. Antral mucosa thickness often exceeded 1.5 to 2 times normal. Antral mucosal erosions occurred in 7 of 44 (16%) monkeys with H. pylori. Argyrophilic bacteria morphologically consistent with H. pylori were present in antral and less commonly cardiac mucosal glands. Intensity of bacterial colonization correlated with lymphoplasmacytic infiltrates (r ϭ 0.754) and hyperplasia (r ϭ 0.700), although responses were quite variable. These bacteria were not detected in fundic mucosa except in instances where parietal cells were substantially depleted in glands coincident with localized increases in lamina propria inflammatory cell infiltrates. Helicobacter heilmannii-like organisms (HHLOs) were present in fundic glands of all 63 monkeys; colonization was often pronounced. Scores for fundic mucosal inflammation did not correlate with presence or intensity of colonization with HHLOs (r ϭ 0.005). Rather, fundic inflammation scores positively correlated with the antral inflammation scores (r ϭ 0.548). Bacteria morphologically, biochemically, and genetically consistent with H. pylori were cultured from gastric mucosal specimens confirming bacterial identification. These findings demonstrate that adolescent cynomolgus monkeys are susceptible to natural infection with H. pylori and develop many morphologic hallmarks of H. pylori-related gastritis in humans.Key words: Animal model; bacteria; gastritis; Gastrospirillum hominis; Helicobacter; Helicobacter heilmannii; Helicobacter pylori; monkey; nonhuman primate; spirochetes; stomach.Spirochetes or spiral-shaped bacteria have long been recognized as constituents of gastric microflora in various mammalian species. 8,29,36,48,55,61,62 38 Most Helicobacter species do not have strict host specificity. Rather, certain species have been isolated from multiple host species and experimental transmission among animal species has been shown. 19,22,31,37,41,52 Suspected zoonotic transmission has also been reported. ...

No abstract

No abstract

Helicobacter hepaticus, a causative agent of chronic hepatitis and hepatocellular carcinoma in mice, expresses a nickel-containing hydrogen-oxidizing hydrogenase enzyme. Growth of a hyaB gene-targeted mutant was unaffected by the presence of hydrogen, unlike the wild-type strain, which showed an enhanced growth rate when supplied with H 2 . Hydrogenase activities in H. hepaticus were constitutive and not dependent on the inclusion of H 2 during growth. Addition of nickel during growth significantly stimulated both urease (for wild-type and hyaB) and hydrogenase (for wild-type) activities. In a 5-h period, the extent of 14 C-labeled amino acid uptake by the wild type was markedly enhanced in the presence of hydrogen and was >5-fold greater than that of the hyaB mutant strain. In the presence of H 2 , the short-term whole-cell amino acid uptake V max of the parent strain was about 2.2-fold greater than for the mutant, but the half-saturation affinity for amino acid transport was the same for the parent and mutant strain. The liver-and cecum-colonizing abilities of the strains was estimated by real-time PCR quantitation of the H. hepaticus-specific cytolethal distending toxin gene and showed similar animal colonization for the hyaB mutant and the wild type. However, at 21 weeks postinoculation, the livers from mice inoculated with wild type exhibited moderate lobular lymphoplasmacytic hepatitis with hepatocytic coagulative necrosis, but the hydrogenase mutants exhibited no histological evidence of lobular inflammation or necrosis.In recent years, more than three different Helicobacter species have been recovered from rodents (24,25,31), with H. hepaticus being the most well-studied enterohepatic Helicobacter species. First isolated in 1992 from untreated A/JCr control mice, H. hepaticus is a gram-negative, microaerophilic bacterium (6) that occurs naturally in many strains of inbred mice (30). Mice infected with this bacterium develop chronic hepatic lesions and are more prone to developing hepatocellular carcinoma (25, 26), which has made H. hepaticus an excellent model for studying mechanisms of bacterium-associated liver carcinogenesis. Although H. hepaticus can be isolated from the liver of infected mice, it is more consistently recovered from the intestinal tract since the primary site of colonization is the lower bowels of mice (6, 7). Recently, Helicobacter species DNA was reported to be associated with primary hepatocellular carcinomas in human liver samples (9, 23).At the same time, a hydrogen uptake hydrogenase enzyme well studied for its roles in nonpathogenic bacteria was demonstrated to be important for colonization of animals by some human pathogens (i.e., by Salmonella enterica serovar Typhimurium and Helicobacter pylori [14,21]); this sparked our interest in studying the physiological role of this enzyme in H. hepaticus (16). The colonization deficiency of hydrogenase structural gene mutants of H. pylori was attributed to their inability to utilize hydrogen as an energy substrate. H. hepaticus hydro...

No abstract