His progression through the academic ranks was a reflection, not only of his outstanding commitment to learning and teaching, but also his stellar research in the field of gut microbiology.During his career, Adrian built a large research team working in different aspects of this broad field, most notably the gut bacterium Helicobacter pylori.Adrian's early research was focussed on curved and spiral-shaped members of the 'normal microflora', now referred to as the 'microbiota'.This was a poorly understood area of microbiology, but 40 years later, has become a particularly hot area of the discipline and recognised for its importance in all aspects of physical and mental wellbeing.Adrian's work on the largely uncharacterised gut bacteria was to draw the interest of future Nobel Laureate, Prof. Barry Marshall, who sought Adrian's guidance regarding curved bacilli that he and Prof. Robin Warren had observed in gastric biopsies of patients with gastritis and peptic ulcers.Many years later, Prof. Marshall invited Adrian to accompany him to the Nobel award ceremony in Sweden in 2005

Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100 000 and 15 000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.

This chapter concentrates on the ultrastructural features of Helicobacter pylori, with limited descriptions of some of the more unusual features seen in the other members of this genus. Certain aspects of the ultrastructural detail of the helicobacters, e.g., sheathed flagella and surface urease, have been implicated in their ability to survive in hostile environments such as the acidic gastric mucosa and their ability to induce disease. Generally it is considered that the spiral morphology and flagella are essential for colonization of gastric and intestinal mucus. By excluding flagellin, urease, and GroEL from their preparations, Doig and Trust were able to describe eight other outer membrane antigens of H. pylori, six of which were shown to be surface exposed. The action of the only monolactam tested, aztreonam, was found to be different, with this antibiotic inducing filamentation in the H. pylori cells, and this was attributed to the fact that this antibiotic was the only one tested that bound preferentially to a single penicillin-binding protein thought to be essential for helical morphology. The identification and characterization of ultrastructural features of H. pylori-infected tissue provide valuable insights into the pathogenesis of Helicobacter infection. However, the use of these characteristics to assess clinical outcomes of the infection is limited. Several bacterial toxins, such as Clostridium botulinum toxin or toxin A from Staphylococcus aureus, are known to cause alterations in cytoskeletal architecture.

The presence of Helicobacter spp. was examined in the liver and in different regions of the gastrointestinal tract (GIT) including the stomach, 3cm above ileum, ileum, caecum, colon and rectum of 10 ringtail possums (RTPs) and 3 koalas using a combination of microscopy, culture and PCR. Helicobacter was detected in the distal end of the GIT of 7 of 10 RTPs by direct PCR and in all (10/10) RTPs by nested PCR. Five ‘S’ shaped isolates with bipolar sheathed flagella were isolated from the lower bowel of 3 of the 10 RTPs. 16S rRNA sequence analysis of these 5 isolates confirmed them as potentially novel Helicobacter species. No Helicobacter species were cultured from the koalas, however Helicobacter DNA was detected, in the majority of liver and/or stomach samples of the three koalas and in the colonic region of one koala, using nested PCR. The 16S rRNA gene was sequenced directly from DNA extracted from the homogenised livers and mucus scrapings of the stomach from koala 1 and were confirmed to be Helicobacter species. Based on histopathological examination of sections from the liver and intestine no evidence of infection could be related to the presence of helicobacters in either the RTP or koala. Based on our results, it is possible that diet may influence the detection of Helicobacter species; however this required further investigation.

The presence of Helicobacter species in Australian marsupials was examined systematically using microscopy, culture, and PCR in different regions of the gastrointestinal tract (GIT) and in the liver of brushtail possums (BTPs) (Trichosurus vulpecula), a common Australian marsupial that feeds on eucalyptus leaves. The spatial distribution of Helicobacter species in the GIT sections also was examined microscopically in silver-stained sections and by fluorescent in situ hybridization (FISH) using a Helicobacter genus-specific probe. Helicobacter species were found colonizing the lower bowel of all BTPs studied. Good agreement was observed between the detection of Helicobacter species using culture and PCR, which was supported by the microscopic examination of silver-stained sections and FISH. The lower bowel of BTPs were colonized by one to three morphologically different (a comma-shaped species with no apparent flagella, a fusiform-shaped species entwined with periplasmic fibers and a bipolar sheathed flagella, and an S-shaped species with bipolar sheathed flagella) and potentially novel Helicobacter species, as well as in one case with a potentially novel Campylobacter species, which was a tightly coiled rod with bipolar unsheathed flagella. The isolation and characterization of these Helicobacter species in BTPs provides important information regarding the specific natural niche of these bacteria and their corelationship within their host, and it increases our understanding of the ecology of Helicobacter species.

BACKGROUND:Lactobacillus and Bifidobacterium species have shown beneficial effects in the treatment of Helicobacter pylori infection; however, the mechanisms behind such effects are not fully understood. In this study, we have investigated the immunomodulatory effects of probiotics in a mouse model of H. pylori infection.MATERIALS AND METHODS:H. pylori-infected C57BL/6 mice were treated with L. casei L26, B. lactis B94, or no probiotics for 5 weeks, respectively. Mice not infected with H. pylori were included as normal controls. Gastric histology, protein levels of interleukin (IL)-1beta, IL-10, IL-12/23p40, and H. pylori colonization density in the gastric tissues, as well as H. pylori-specific antibodies were examined.RESULTS:In mice receiving L. casei L26 and B. lactis B94, gastric neutrophil infiltration and IL-1beta were significantly decreased and IL-10 was significantly increased as compared with mice receiving no probiotics. In mice receiving B. lactis B94, IL-12/23p40 was significantly increased and H. pylori IgG was significantly reduced as compared with mice receiving no probiotics. No significant difference of H. pylori colonization was observed among the three groups of mice.CONCLUSION:The reduced level of IL-1beta and neutrophil infiltration observed in mice infected with H. pylori following treatment with L. casei L26 and B. lactis B94 resulted from a modulation of immune response rather than a decrease of H. pylori colonization. Furthermore, B. lactis B94 has the intrinsic ability to promote a Th1 immune response through an increase in IL-12/IL-23.

We have previously shown that long-term infection of BALB/c mice with gastric Helicobacter species results in the development of histopathological lesions that resemble those seen in patients diagnosed with gastric mucosa associated lymphoid tissue (MALT) lymphoma. This paper describes analysis of this disease at the molecular level through the use of microarray technology and immunohistochemical staining. We were able to monitor the genetic changes in the gastric mucosa characterized by distinct transcriptional signatures and correlate these with histological changes as the infection progressed from a chronic inflammatory infiltrate through to MALT lymphoma. This model system also enabled us to further dissect the role of antigen presentation and prophylactic immunization in the disease process. Antimicrobial therapy to eradicate the antigen correlated with significant reduction in pathology and major changes in the gene expression profile. Subsequent reintroduction of the antigen resulted in rapid tumor development which correlated with an increase in aggressively proliferating cells and changes in the cellular composition of the tumor. The response in vaccinated animals showed that the protected animals exhibited a strikingly different transcriptional profile compared to those of non-protected or control mice, indicating that the vaccination targeted the appropriate site leaving a long-lasting signature. The genes which were most significantly up-regulated included a number of adipocyte-specific factors, such as fat-cell specific cytokines and adipocyte surface markers. This study allowed for us to highlight the significance of antigen presentation in this disease and to hypothesis mechanisms associated with protective immunity.

Bacterial ssrA encodes tmRNA that functions both as a tRNA and an mRNA to rescue the stalled ribosome on defective mRNAs. In this study, ssrA was identified in four gastric species of Helicobacters and four enterohepatic species of Helicobacters . The tag peptide of 14 amino acids encoded by ssrA showed a pattern of Val 1 Ala 13 in gastric species, a pattern of Ala 1 Val 13 in enterohepatic species, in contrast to the pattern of Ala 1 Ala 13 in W. succinogenes and C. jejuni , which are closely related to helicobacters. Phylogenetic analysis and the patterns of the tag peptide suggest that the Helicobacter genus could be separated into two genera. High conservation of ssrA in H. pylori was observed. The annotated ORF HP0784 in H. pylori , which largely overlaps ssrA , is unlikely to be functional. H. pylori ssrA interestingly expressed a large and a small tmRNA molecule.

BACKGROUND:Helicobacter pylori is a causative agent of gastric and duodenal ulcers and gastric cancer. Its urease enzyme allows survival in acid conditions and drives bacterial intracellular metabolism. We aimed to investigate the role of urease in determining the intragastric distribution of Helicobacter species in vivo.MATERIALS AND METHODS:The C57BL/6 mouse model of gastritis was used for infection with Helicobacter felis (CS1) or H. pylori (SS1). Urease-modulating compounds urea and/or fluorofamide (urease inhibitor) were administered to mice over 7 days. Concurrent gastric acid inhibition by omeprazole was also examined. Bacterial distribution in the antrum, body, antrum/body, and body/cardia transitional zones was graded "blindly" by histologic evaluation. Bacterial colony counts on corresponding tissue were also conducted.RESULTS:Urease inhibition by fluorofamide decreased H. pylori survival in most gastric regions (p < .05); however, there were no marked changes to H. felis colonization after this treatment. There was a consistent trend for decreased antral colonization, and an increase in antrum/body transitional zone and body colonization with excess 5% or 6% (w/v) urea treatment. Significant reductions of both Helicobacter species were observed with the co-treatment of urea and fluorofamide (p < .05). Collateral treatment with omeprazole did not alter H. pylori colonization patterns caused by urea/fluorofamide.CONCLUSIONS:Urease perturbations affect colonization patterns of Helicobacter species. Combined urea and fluorofamide treatment reduced the density of both Helicobacter species in our infection model.

The acceptance of Helicobacter pylori as a major human pathogen has necessitated the development of animal models to help elucidate the pathogenic mechanisms of this bacterium and aid in the development of improved strategies for the treatment of gastric disease. Appropriate models, utilising a range of animal species, have been developed to examine factors such as the influence of host responses and bacterial factors in disease development and the success of new therapeutic regimens, including vaccination, to cure infection.

HelicobacterVolume 7, Issue 2 p. 140-141 Response to Letter by Crabtree et al. Adrian Lee, Adrian Lee Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this authorHazel Mitchell, Hazel Mitchell Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this authorJani O’Rourke, Jani O’Rourke Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this author Adrian Lee, Adrian Lee Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this authorHazel Mitchell, Hazel Mitchell Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this authorJani O’Rourke, Jani O’Rourke Department of Microbiology & Immunology, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, AustraliaSearch for more papers by this author First published: 23 November 2002 https://doi.org/10.1046/j.1083-4389.2002.00072.xCitations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume7, Issue2April 2002Pages 140-141 RelatedInformation

This study describes the molecular makeup of the cell‐wall lipopolysaccharides (LPSs) (O‐chain polysaccharide→core oligosaccharide→lipid A) from five Helicobacter pylori strains: H. pylori 26695 and J99, the complete genome sequences of which have been published, the established mouse model Sydney strain (SS1), and the symptomatic strains P466 and UA915. All chemical and serological experiments were performed on the intact LPSs. H. pylori 26695 and SS1 possessed either a low‐Mr semi‐rough‐form LPS carrying mostly a single Ley type‐2 blood‐group determinant in the O‐chain region covalently attached to the core oligosaccharide or a high‐Mr smooth‐form LPS, as did strain J99, with an elongated partially fucosylated type‐2 N‐acetyllactosamine (polyLacNAc) O‐chain polymer, terminated mainly by a Lex blood‐group determinant, connected to the core oligosaccharide. In the midst of semi‐rough‐form LPS glycoforms, H. pylori 26695 and SS1 also expressed in the O‐chain region a difucosylated antigen, α‐l‐Fucp(1–3)‐α‐l‐Fucp(1–4)‐β‐d‐GlcpNAc, and the cancer‐cell‐related type‐1 or type‐2 linear B‐blood‐group antigen, α‐d‐Galp(1–3)‐β‐d‐Galp(1–3 or 4)‐β‐d‐GlcpNAc. The LPS of H. pylori strain P466 carried the cancer‐associated type‐2 sialyl Lex blood‐group antigen, and the LPS from strain UA915 expressed a type‐1 Leb blood‐group unit. These findings should aid investigations that focus on identifying and characterizing genes responsible for LPS biosynthesis in genomic strains 26695 and J99, and in understanding the role of H. pylori LPS in animal model studies. The LPSs from the H. pylori strains studied to date were grouped into specific glycotype families.

AGAA761'p=0.03 vs. non-tumour; "p=O.05vs, antrum, "p=O.06VS. corpus; '''p=O.01 vs. non-tumour first-degree relatives, and is also significantly increased in H. pylori infected individuals.

peptic ulceration than slb or s2 strains, vacA diversity among strains from South Africa has not previously been examined, but non-existence of pathogenic types could explain the 'African enigma' of high levels of infection but relatively low levels of disease We aimed to assess vacA diversity and the utility of our vacA typing system in this South African population.Methods.We examined single colony isolates from 16 South African patients, 15 Black or coloured and 1 White, median age 36 years (range 20-63).Eleven were male, 11 had active duodenal ulcers (and were not taking NSAIDs) and 4 were asymptomatic without ulcers.In 3 cases, 2 morphologically distinct colonies were examined.Chromosomal DNA was extracted from plate