RFLP and RAPD Analysis of <i>In Vivo</i> Genetic Interactions Between Strains of <i>Helicobacter pylori</i>

Danon, Stephen J.; Luria, Brian J.; Mankoski, Raymond; Eaton, Kathryn A.

doi:10.1046/j.1523-5378.1998.08010.x

Cited by 13 publications

(11 citation statements)

References 17 publications

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“…Once established, a strain could interfere with the establishment of a subsequent strain even when the latter was more fit to colonize mice. This phenomenon was previously described by Danon et al, who showed that the implantation of a first strain in the mouse could prevent the implantation of a mixture of other strains (7). This finding could be the consequence of the immune response against the first strain (IS) being strong enough to inhibit the implantation of the second strain.…”

Section: Discussionsupporting

confidence: 57%

Modification in the ppk Gene of Helicobacter pylori during Single and Multiple Experimental Murine Infections

et al. 2003

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The bacterial pathogen Helicobacter pylori is highly adapted to the human stomach, and a high level of polymorphism is observed among clinical isolates. This polymorphism may be the consequence of adaptive changes during colonization, making a strain better able to survive, to evade the immune system, and to provoke a chronic infection. To investigate the mechanisms involved in the acquisition of diversity in H. pylori, mouse models of single infections, coinfections, and superinfections were developed. These experimental infections were conducted with strain SS1, well known to be mouse adapted, and with two strains freshly isolated from infected patients: Hp141 and Hp145. Genetic modifications occurring in these strains were studied over time by comparing randomly selected colonies of the emerging strains to those of the infecting strains by using randomly amplified polymorphic DNA fingerprinting with six different primers and by using PCR to amplify the vacA and cagA genes. We showed that, regardless of the number of infecting strains, only one emerged from the animals and that the establishment of a first strain thwarted the implantation of a second strain. During both a single infection and a coinfection with SS1, Hp141 was replaced by a genetic variant (Hp141v) that overcame SS1 in coinfection experiments. Hp141v exhibited a deletion of a 102-bp repeated sequence within the ppk gene, which encodes polyphosphate kinase (PPK), an enzyme involved in the physiological adaptation of the microbial cell to nutritional and environmental stresses. The deletion led to higher enzymatic activity of PPK, and the variant exhibited a better capacity to colonize mice. Considering that the modified gene is known to be involved in adaptation to a new environment, our results are consistent with an adaptive change in strain Hp141 and suggest that PPK is an important virulence factor in H. pylori.Helicobacter pylori is a gastrointestinal pathogen that colonizes the human stomach and is involved in chronic gastritis, peptic ulceration, and gastric carcinoma (25,32,40). Certain strains are able to infect animals, such as mice, which can be used as experimental infection models (13,24). H. pylori is one of the bacteria that show the highest level of genetic polymorphism (1). The mechanisms leading to the diversity of H. pylori include mutation; intrachromosomal shift; variations in the locations of insertion sequences; mosaicism of genes, such as vacA; deletion of others, such as those included in the cag pathogenicity island; and recombination between strains coinfecting the same host (17, 23). The polymorphism of H. pylori could be the consequence of adaptive events during colonization of the human stomach, making a strain more efficient at evading the immune system and thus at surviving and provoking a long-term infection (29,39).In order to study the genetic changes in H. pylori that may occur during an infection, we developed a mouse model with strain SS1, previously adapted to this animal, and two strains freshly isolated f...

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Section: Discussionsupporting

confidence: 57%

Modification in the ppk Gene of Helicobacter pylori during Single and Multiple Experimental Murine Infections

et al. 2003

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“…They found that only one bacterial strain emerged, and it was usually the primary strain. These results are supported by Danon et al, where some evidence is provided that an established H. pylori strain can prevent colonization by a challenging strain (14). In contrast, with two different mouse-adapted strains of H. pylori that colonize distinct stomach regions, Akada et al showed that both strains can simultaneously infect, and superinfection does not alter colonization of either strain (1).…”

Section: Discussionmentioning

confidence: 78%

Chemotaxis Plays Multiple Roles during Helicobacter pylori Animal Infection

et al. 2005

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Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori. We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW, cheA, or cheY are all nonchemotactic and infect FVB/N mice with an attenuated phenotype after 2 weeks of infection. If infections proceeded for 6 months, however, this attenuation disappeared. Histological and culture analysis revealed that nonchemotactic mutants were found only in the corpus of the stomach, while the wild type occupied both the corpus and the antrum. Further analysis showed that nonchemotactic H. pylori isolates had an increased 50% infectious dose and were greatly outcompeted when coinfected with the wild type. If nonchemotactic mutants were allowed to establish an infection, subsequent infection with the wild type partially displaced the nonchemotactic mutants, indicating a role for chemotaxis in maintenance of infection. The data presented here support four roles for chemotaxis in H. pylori mouse infections: (i) establishing infection, (ii) achieving high-level infection, (iii) maintaining an infection when there are competing H. pylori present, and (iv) colonizing all regions of the stomach.Helicobacter pylori is a motile, chemotactic bacterium that colonizes the stomachs of ϳ50% of the world's population (13). Infection with H. pylori can persist throughout the lifetime of the host and can cause symptoms ranging from mild gastritis to gastric and duodenal ulcers to cancers, such as mucosa-associated lymphoid tissue (MALT) lymphoma and gastric adenocarcinoma (4, 39).Motility and chemotaxis, directed swimming, are survival factors for many bacterial species. Both motility and chemotaxis aid commensal and pathogenic infections, but little is known of the precise benefits of these processes. For example, the 50% lethal dose (LD 50 ) of Vibrio anguillarum nonchemotactic mutants for trout is increased 400-fold (28) (for reviews see references 22 and 30). In contrast, some nonchemotactic mutants of V. cholerae colonize infant mice better than does the wild type, in part at least because they occupy a larger portion of the gastrointestinal tract (11,20). In most of these cases, however, it is not known why motility mutants fare differently than the wild type. H. pylori is an excellent organism with which to ascertain motility's role in infection, because this bacterium is thought to lack a significant environmental niche outside of the human host and, thus, likely uses motility and chemotaxis within the host. In fact, disruption of genes involved in either motility or chemotaxis attenuates colonization of mice and piglets (16,17,19,24,29). Although these findings indicate that motility and chemotaxis play important roles during...

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“…Using the silver-stained slides from the 6-and 15-month time points, five areas of the stomach (antrum, antrum-body transitional zone, body, body-cardium transitional zone, and cardium regions) were assessed for the level and presence of bacteria using a grading system from 0 to 4 as described previously (9,36). Briefly, a grade of 0 indicates no bacteria observed, while a grade of 4 indicates heavy colonization where all crypts were densely packed.…”

Section: Mouse Infections (I) Isolation Of New Mouse-colonizing Stramentioning

confidence: 99%

“…The mouse-adapted SS2000 strain colonized to a level approximately 0.5 log unit higher than the pre-mouse-adapted strain (PMSS2000) in C57BL/6 mice; thus, some host adaptation appears to have occurred during the isolation of this strain. Host adaptation of H. pylori has been reported to occur in mice (9,31,39), gerbils (23), primates (11), piglets (15), and humans (18,24,25). The mechanisms of these adaptations are largely unknown, although they are likely to involve genomic variations (3,18).…”

Section: Vol 72 2004 Chronic H Pylori Infection In the Mouse Modelmentioning

confidence: 99%

ChronicHelicobacter pyloriInfection with Sydney Strain 1 and a Newly Identified Mouse-Adapted Strain (Sydney Strain 2000) in C57BL/6 and BALB/c Mice

et al. 2004

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The mouse model of Helicobacter pylori-induced disease using Sydney strain 1 (SS1) has been used extensively in Helicobacter research. Herein we describe the isolation and characterization of a new mouse-colonizing strain for use in comparative studies. One strain capable of persistent mouse colonization was isolated from a total of 110 clinical isolates and is named here SS2000 (Sydney strain 2000). Genome typing revealed a number of differences between SS1 and SS2000 as well as between them and the respective original clinical isolates. In particular, SS2000 lacked the entire cag pathogenicity island, while SS1 contained all 27 genes of the island. C57BL/6 and BALB/c mice were infected with SS1 or SS2000 or were treated with broth medium (controls). After 6 months host-specific effects were evident, including lower colonization levels in the BALB/c animals. Few pathological differences were observed between SS1-and SS2000-infected animals. However, by 15 months postinfection, SS1-infected C57BL/6 mice had developed more severe gastritis than the SS2000-infected animals. In contrast SS2000-infected BALB/c mice showed increased accumulation of mucosa-associated lymphoid tissue compared to those infected with SS1. This improved comparative model of H. pyloriinduced disease allowed dissection of both host and strain effects and thus will prove useful in further studies.Mouse models of Helicobacter pylori-induced disease have been extensively used in Helicobacter research and have been particularly useful in the elucidation of factors required for colonization, distribution and persistence of infection (10,29,31), the contribution of various virulence factors (some examples are given in references 12 and 43), and the development of vaccines (reviewed in reference 28). Early mouse model infection studies utilized Helicobacter felis, a close relative of H. pylori, because no H. pylori strains persistently colonized mice (5, 29). In 1997, Lee et al. isolated H. pylori Sydney strain 1 (SS1) by screening a number of clinical isolates for their ability to colonize mice using a novel technique where a number of strains were pooled and passaged from mouse to mouse. SS1 was found to consistently colonize multiple strains of mice to a high level and to establish infection that persisted over many months, thus providing an ideal opportunity to study the effects of chronic infection and host specificity in this small rodent model (31). The difficulty in finding additional H. pylori strains that persistently colonize mice has hindered studies of strainspecific effects on infection and immunity. Other groups have attempted to isolate new mouse-colonizing strains, but in most cases those strains utilized do not colonize efficiently and often do so only transiently (some examples are given in references 34, 39, and 47). The SS1 mouse model has provided important information regarding H. pylori-related disease, particularly with respect to colonization properties. However, given the lack of well-scrutinized and characterized mouse-...

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RFLP and RAPD Analysis of In Vivo Genetic Interactions Between Strains of Helicobacter pylori

Abstract: These findings support the development of genetic heterogeneity of H. pylori during long-term colonization either by genetic drift or by in vivo recombination. Such genomic modification in vivo could explain the naturally occurring heterogeneity of H. pylori.

Cited by 13 publications

References 17 publications

Modification in the ppk Gene of Helicobacter pylori during Single and Multiple Experimental Murine Infections

Modification in the ppk Gene of Helicobacter pylori during Single and Multiple Experimental Murine Infections

Chemotaxis Plays Multiple Roles during Helicobacter pylori Animal Infection

ChronicHelicobacter pyloriInfection with Sydney Strain 1 and a Newly Identified Mouse-Adapted Strain (Sydney Strain 2000) in C57BL/6 and BALB/c Mice

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