Animal Models of Helicobacter-Induced Disease: Methods to Successfully Infect the Mouse [chapter]

available in PMC 2013 January 15Animal models of microbial diseases in humans are an essential component for determining fulfillment of Koch’s postulates and determining how the organism causes disease, host response(s), disease prevention, and treatment. In the case of Helicobacter pylori, establishing an animal model to fulfill Koch’s postulates initially proved so challenging that out of frustration a human volunteer undertook an experiment to become infected with H. pylori and to monitor disease progression in order to determine if it did cause gastritis. For the discovery of the organism and his fulfillment of Koch’s postulates he and a colleague were awarded the Nobel Prize in Medicine. After H. pylori was established as a gastric pathogen, it took several years before a model was developed in mice, opening the study of the organism and its pathogenicity to the general scientific community. However, while the model is widely utilized, there are a number of difficulties that can arise and need to be overcome. The purpose of this chapter is to raise awareness regarding the problems, and to offer reliable protocols for successfully establishing the H. pylori mouse model

Draft Genome Sequences of Eight Enterohepatic Helicobacter Species Isolated from Both Laboratory and Wild Rodents

The draft genome sequences of eight enterohepatic Helicobacter species, H. muridarum, H. trogontum, H. typhlonius, and five unnamed helicobacters, are presented here. Using laboratory mice pervasively infected with helicobacters, we characterized the presence of known virulence factors.National Institutes of Health (U.S.) (grant R01CA067529)National Institutes of Health (U.S.) (grant R01OD011141)National Institutes of Health (U.S.) (grant P01CA26731)National Institutes of Health (U.S.) (grant P30ES002109

Implementing tradable permits for sulfur oxides emissions : a case study in the South Coast Air Basin

Tradable emissions permits have important theoretical advantages over source-specific technical standards as a means for controlling pollution. Nonetheless, difficulties can arise in trying to implement an efficient, competitive market in emissions permits. Simple workable versions of the market concept may fail to achieve the competitive equilibrium, or to take account of important complexities in the relationship between the pattern of emissions and the geographical distribution of pollution. Existing regulatory law may severely limit the range of market opportunities that states can adopt. This report examines the feasibility of tradable permits for controlling particulate sulfates in the Los Angeles airshed. Although the empirical part of the paper deals with a specific case, the methods developed have general applicability. Moreover, the particular market design that is proposed -- an auction process that involves no net revenue collection by the state -- has attractive features as a general model

Spatial and temporal colonization dynamics of segmented filamentous bacteria is influenced by gender, age and experimental infection with Helicobacter hepaticus in Swiss Webster mice

In this study, we examined colonization dynamics of segmented filamentous bacteria (SFB) in intestine of Swiss Webster (SW) mice infected with Helicobacter hepaticus (Hh). At 8 weeks post-inoculation with Hh (WPI), cecal and colonic SFB levels in the control males were significantly lower compared to those at 16 WPI. Hh infection in both genders did not alter SFB levels in the jejunum and ileum, but increased SFB levels in the cecum and colon of males compared to the controls (P < 0.05) at 8 WPI. At 16 WPI, the Hh-infected females contained lower levels of SFB in the jejunum, cecum and colon compared to the female controls. Irrespective of gender, aging and Hh infection, the Il-17A mRNA levels decreased from the small intestine to the cecum and then to the colon, whereas the Foxp3 mRNA levels were comparable in these intestinal regions. There were significant differences in Il-17A mRNA levels in the ileum (P < 0.05, R2 = 0.31), with females having greater Il-17A mRNA levels than males, and higher SFB colonization levels related to more Il-17A mRNA. These results indicate that aging and gender play an important role in colonization dynamics of intestinal SFB and ileal SFB-associated Th17 response.United States. National Institutes of Health (P30-ES002109)United States. National Institutes of Health (R01OD11141)United States. National Institutes of Health (R01-CA067529

The Passing of Print

This paper argues that ephemera is a key instrument of cultural memory, marking the things intended to be forgotten. This important role means that when ephemera survives, whether accidentally or deliberately, it does so despite itself. These survivals, because they evoke all those other objects that have necessarily been forgotten, can be described as uncanny. The paper is divided into three main sections. The first situates ephemera within an uncanny economy of memory and forgetting. The second focuses on ephemera at a particular historical moment, the industrialization of print in the nineteenth century. This section considers the liminal place of newspapers and periodicals in this period, positioned as both provisional media for information as well as objects of record. The third section introduces a new configuration of technologies – scanners, computers, hard disks, monitors, the various connections between them – and considers the conditions under which born-digital ephemera can linger and return. Through this analysis, the paper concludes by considering digital technologies as an apparatus of memory, setting out what is required if we are not to be doubly haunted by the printed ephemera within the digital archive

Helicobacter hepaticus Cholesterol-α-glucosyltransferase is Essential for Establishing Colonization in Male A/JCr Mice

Background Helicobacter pylori cholesterol-α-glucosyltransferase (cgt) is essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the H. pylori cgt. However, the role of cgt in the pathogenesis of H. hepaticus has not been investigated. Materials and Methods Two cgt-deficient isogenic mutants of wild-type H. hepaticus (WT) 3B1 were generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization levels of the mutants and WT 3B1 as well as select inflammation-associated cytokines were measured by qPCR at 4 months postinoculation. Results Both mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10 mice inoculated with WT 3B1 were qPCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation (p < .05) and also produced significantly lower hepatic mRNA levels of proinflammatory cytokines Ifn-γ (p < .01) and Tnf-α (p ≤ .02) as well as anti-inflammatory factors Il10 and Foxp3 compared with the WT 3B1-inoculated mice. Additionally, the WT 3B1-inoculated mice developed significantly higher Th1-associated IgG2a (p < .0001) and Th2-associated IgG1 responses (p < .0001) to H. hepaticus infection than mice dosed with isogenic cgt mutants. Conclusion Our data indicate that the cholesterol-α-glucosyltransferase is required for establishing colonization of the intestine and liver and therefore plays a critical role in the pathogenesis of H. hepaticus.National Institutes of Health (U.S.) (Grant R010D011141)National Institutes of Health (U.S.) (Grant 01CA026731)National Institutes of Health (U.S.) (Grant R01AT004326)National Institutes of Health (U.S.) (Grant P30-ES002109

Whole-Genome Sequences and Classification of

In collaboration with the CDC’s Streptococcus Laboratory, we report here the whole-genome sequences of seven Streptococcus agalactiae bacteria isolated from laboratory-reared Long-Evans rats. Four of the S. agalactiae isolates were associated with morbidity accompanied by endocarditis, metritis, and fatal septicemia, providing an opportunity for comparative genomic analysis of this opportunistic pathogen.United States. National Institutes of Health (T32-OD010978)United States. National Institutes of Health (P30-ES002109

Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography

Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.National Institutes of Health (U.S.) (T320D010978-26)National Institutes of Health (U.S.) (P01CA028842-23)National Institutes of Health (U.S.) (P30ES002109

Minimal standards for describing new species belonging to the families Campylobacteraceae and Helicobacteraceae : Campylobacter, Arcobacter, Helicobacter and Wolinella spp.

Ongoing changes in taxonomic methods, and in the rapid development of the taxonomic structure of species assigned to the Epsilonproteobacteria have lead the International Committee of Systematic Bacteriology Subcommittee on the Taxonomy of Campylobacter and Related Bacteria to discuss significant updates to previous minimal standards for describing new species of Campylobacteraceae and Helicobacteraceae. This paper is the result of these discussions and proposes minimum requirements for the description of new species belonging to the families Campylobacteraceae and Helicobacteraceae, thus including species in Campylobacter, Arcobacter, Helicobacter, and Wolinella. The core underlying principle remains the use of appropriate phenotypic and genotypic methods to characterise strains sufficiently so as to effectively and unambiguously determine their taxonomic position in these families, and provide adequate means by which the new taxon can be distinguished from extant species and subspecies. This polyphasic taxonomic approach demands the use of appropriate reference data for comparison to ensure the novelty of proposed new taxa, and the recommended study of at least five strains to enable species diversity to be assessed. Methodological approaches for phenotypic and genotypic (including whole-genome sequence comparisons) characterisation are recommended

Draft Genome Sequences of Five Novel Polyketide Synthetase-Containing Mouse

We report herein the draft genomes of five novel Escherichia coli strains isolated from surveillance and experimental mice housed at MIT and the Whitehead Institute and describe their genomic characteristics in context with the polyketide synthetase (PKS)-containing pathogenic E. coli strains NC101, IHE3034, and A192PP.National Institutes of Health (U.S.) (P30-ES002109)National Institutes of Health (U.S.) (T32OD010978)National Institutes of Health (U.S.) (R010D0111141