Helicobacter spp. Other Than Helicobacter pylori

Non- H. pylori Helicobacter species (NHPHS) are associated with several important human and animal diseases. In the past year research into this group of bacteria has continued to gain attention, and novel species have been described in new niches owing to improvements in detection methods. Polymerase chain reaction and/or sequencing remain the gold standard for the detection of this genus. New insights into the pathogenesis of the NHPHS in hepatobiliary, gastric, and intestinal diseases were gained. In particular, data revealed interaction between hepatic steatosis and infectious hepatitis in the development of hepatocellular carcinoma. Evidence of an association between hepatitis C virus and Helicobacter spp. in hepatocarcinoma development was also provided; and male sex hormone signaling appeared to influence infectious hepatitis induced by Helicobacter hepaticus . More findings support an association between Helicobacter heilmannii and gastric adenocarcinoma; and in mice, mucins MUC4 and MUC5 but not MUC1 influence the colonization and pathogenesis of Helicobacter felis . Data indicated that the roles of the adaptive immune system in H. hepaticus -induced intestinal tumorigenesis are different in the small and large intestines, and environmental factors, such as bile acids may modulate H. hepaticus carcinogenic potential. New reports in the prevention and eradication of NHPHS showed a protective response against Helicobacter suis induced by vaccine administration, and a successful cross-foster rederivation method successfully eradicated Helicobacter spp. from contaminated mice litters. Overall, the studies provided insights into the pathophysiology of Helicobacter species other than Helicobacter pylori.     

Helicobacter exposed

Helicobacter pylori Protocolsedited by C.L. Clayton and H.L. Mobley, Humana Press, 1997. Hardback US $89.50 (xiii+274 pages) ISBN 0 896 033 813     

Extragastric manifestations of Helicobacter pylori infection--other Helicobacter species

Recent studies have indicated a strong link between Helicobacter pylori and idiopathic thrombocytopenic purpura and iron deficiency anemia. Interesting results have also been obtained for ischemic heart disease, though most putative associations between H. pylori infection and extragastric disease remain speculative. With regard to other Helicobacter species, Helicobacter felis has been shown to play a role in gastric carcinogenesis in mouse models. An increased susceptibility to cholesterol gallstone formation has been described in animals fed a lithogenic diet and infected with Helicobacter bilis, or co-infected with Helicobacter hepaticus and Helicobacter rodentium. Finally, enterohepatic Helicobacter species have also been exploited to better understand inflammatory bowel disease.     

Helicobacter pylori motility

Motility is essential for Helicobacter pylori colonization. This review discusses the biochemistry, genetics and genomics of the H. pylori flagellum, and compares these features with well-characterized bacteria.     

Helicobacter pylori catalase

Helicobacter pylori is the major aetiological agent of gastroduodenitis in humans. Due to the potential importance of catalase in the growth and survival of Helicobacter pylori on the surface of inflamed mucosae, we have characterized catalase from H. pylori as a prelude to further studies on the function of the enzyme in vivo. The catalase activity of H. pylori was significantly affected by the presence of blood, serum or erythrocytes in the growth medium: the greatest activity was expressed when the bacterium was grown on medium containing serum. H. pylori catalase is a tetramer with a subunit Mr of 50,000. The enzyme had a pI of 9.0-9.3, was active over a broad pH range and was stable at 56 degrees C. It was non-competitively inhibited by sodium azide, and had no detectable peroxidase activity. The Km for the purified catalase was measured as 43 +/- 3 mM-H2O2 and the V as 60 +/- 3 mmol H2O2 min-1 (mg protein)-1. The native catalase has absorption maxima at 280 nm and 405 nm with further minor shoulders or peaks at 510 nm, 535 nm and 625 nm, consistent with the presence of an iron-porphyrin prosthetic group.     

Immunogenic proteins of Helicobacter pullorum,Helicobacter bilis and Helicobacter hepaticus identified by two-dimensional gel electrophoresis and immunoblotting

The ecological niches occupied by various species of Helicobacter are not yet known and the full spectrum of diseases associated with Helicobacter infections are not yet defined. Since these fastidious microaerofilic bacteria require special growth conditions new and improved molecular and serologic diagnostic methods have been developed to increase our understanding of their pathogenesis and virulence characteristics. Immunogenic cell surface proteins of Helicobacter pullorum, Helicobacter bilis, and Helicobacter hepaticus were characterised by proteomic techniques using two-dimensional electrophoresis and immunoblotting with antisera from immunised rabbits. Cross-reactivity between the three Helicobacter species were analysed after a four-step cross-absorption experiment. For H. pullorum, H. bilis and H. hepaticus 21, 13 and 27 specific immunogenic proteins, respectively, were identified. These proteins could be of important sero-diagnostic value for analyses of sera from humans, laboratory animals and for the veterinarian field.     

Genomics of Helicobacter pylori

During this review period, we have definitely entered into the genomic era. The Helicobacter pylori studies reported here illustrate the use of most of the technologies currently available to globally interrogate the genome of a pathogen. Global analysis of the gene content of H. pylori strains gives insight into the extent of its genetic diversity and its in vivo evolution. Our understanding of the particularities of H. pylori as a gastric pathogen colonizing a unique niche has been improved by studies aimed at: (i) the identification of H. pylori-specific genes; (ii) the establishment of correlations between the presence of one or a group of genes (or proteins) with clinical outcome; and (iii) the analysis of global regulatory circuits or responses to the extracellular signals. The response of host cells to H. pylori infection will be developed in the chapter 'H. pylori and gastric malignancies' by Sepulveda and Coehlo. Despite our knowledge of the H. pylori genome, the function of about one third of its total proteins is still unknown. Functional genomics are straightforward approaches for the identification of new gene functions or metabolic pathways as well as for the understanding of cellular processes and the detection of new virulence factors. In silico studies combined with experimental work will undoubtedly continue to develop. To date, the expansion of proteomics with refinements in mass spectrometry technology has illustrated that through immunoproteomics and comparative studies, relevant novel antigens can be identified. Genomics not only provides invaluable information on H. pylori but also opens new perspectives for diagnostic or therapeutic applications.     

Helicobacter and Gastric Malignancies

Individuals infected with Helicobacter pylori , a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of environmental, host genetic, and bacterial factors associated with risk of gastric cancer, to molecular and cell biology approaches aiming at understanding the interaction between H. pylori and the transforming epithelial cell. In this review an account of the last year's research activity on the relationship between H. pylori and gastric cancer will be given.     

Differentiation of clinical Helicobacter pullorum isolates from related Helicobacter and Campylobacter species

Background. Helicobacter pullorum, first detected in the liver and intestinal contents of poultry, was defined as a new species in 1994. This organism has since been isolated from humans with gastroenteritis. Phenotypic as well as genotypic methods have been used to identify H. pullorum associated with cases of human disease. Materials and Methods. Clinical isolates were submitted for identification to the National Laboratory for Enteric Pathogens by Provincial Public Health Laboratories within Canada. Phenotypic characterization was conducted using a variety of growth and biochemical tests including oxidase, catalase, indoxyl acetate, H₂S production in triple sugar iron (TSI) agar, antimicrobial susceptibility testing, and fatty acid analysis. Genotypic identification was performed using a polymerase chain reaction–restriction fragment–length polymorphism (PCR‐RFLP) analysis of a 1‐kb fragment of the Helicobacter 16S rRNA gene. Results. During the last 7 years (1993–1999) a total of 11 isolates of H. pullorum were detected from patients with gastroenteritis for inclusion in this study. Typically, these isolates were oxidase and catalase positive, produced optimal growth at 42°C, and produced H₂S in TSI. Of these 11 isolates, 1 showed DNase activity, while another did not produce H₂S in TSI, and only 2 showed tolerance to 1% bile. Antimicrobial susceptibility assays indicated that 6 of the 11 strains were resistant to nalidixic acid. The fatty acid profiles of the isolates were similar to each other and provided a distinguishing profile from the other related species. Genetically identical and distinct species‐specific restriction fragment–length polymorphism (RFLP) patterns were produced using the restriction enzymes Bsr I and Dde I. Conclusion. Phenotypic and genotypic procedures were used to identify H. pullorum. Interspecies phenotypic variability was apparent and supported the use of a polyphasic approach for identification. Similarities to the more prominent human pathogens Campylobacter coli and C. lari were also noted. The use of a combination of phenotypic and, in particular, genotypic markers for H. pullorum should prove valuable both for epidemiological investigations and for the diagnosis of disease related to this emerging human pathogen.     

Detection of non-pylori Helicobacter species in "Helicobacter heilmannii"-infected humans

BACKGROUND: A small proportion of patients suffering from chronic active gastritis are diagnosed with gastric Helicobacter species other than Helicobacter pylori. Circumstantial evidence has suggested that these bacteria, also referred to as "Helicobacter heilmannii"-like organisms (HHLO), may be transmitted through animals. The isolation of a Helicobacter bizzozeronii strain from a human patient confirmed this hypothesis. It was the aim of the present study to assess the presence of animal Helicobacter species and H. pylori in humans infected with HHLO, as diagnosed by histology. METHODS: Paraffin-embedded gastric biopsy specimens of 108 HHLO-infected patients (42 women and 66 men) from three clinical centers were screened for the presence of animal gastric Helicobacter species by polymerase chain reaction (PCR), using assays targeting the 16S rDNA region of the three known canine and feline helicobacters (H. bizzozeronii, H. salomonis and H. felis), "Candidatus H. suis", and "Candidatus H. bovis". In addition, the presence of H. pylori was evaluated by multiplex PCR analysis. RESULTS: In 63.4% of the stomachs (64/101) classification of the Helicobacter infection into the above mentioned groups was achieved. Non-pylori Helicobacter species commonly colonizing the stomachs of cats and dogs were found in 48.5% (49/101) of the patients. Fourteen (13.9%) samples tested positive for "Candidatus H. suis", and "Candidatus H. bovis" was demonstrated in 1 (0.9%) patient. The presence of H. pylori was established in 13 patients (12.9%). Eleven stomachs (10.9%) were infected with at least two different Helicobacter species. CONCLUSIONS: This study identifies animal Helicobacter species in the stomach of a large series of HHLO-infected patients, which may have clinical implications in a subset of patients with gastric disease.