Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

Wiedemann, Tobias; Loell, Eva; Mueller, Susanna; Stoeckelhuber, Mechthild; Stolte, Manfred; Haas, Rainer; Rieder, Gabriele

doi:10.1371/journal.pone.0004754

Cited by 55 publications

(76 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RNA from gerbil tissue was prepared for quantitative PCR (qPCR) as previously described for mouse tissue (35). qPCR was performed as described previously (35,36), using oligonucleotide primers directed against gerbil GAPDH (glyceraldehyde-3-phosphate dehydrogenase), gerbil IL-10, gerbil gamma interferon (IFN-␥) (37), gerbil IL-6 (38), and gerbil inducible nitric oxide synthase (iNOS) (39). Primer sequences are available upon request.…”

Section: Methodsmentioning

confidence: 99%

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

et al. 2013

View full text Add to dashboard Cite

cHelicobacter pylori maintains colonization in its human host using a limited set of taxis sensors. TlpD is a proposed energy taxis sensor of H. pylori and dominant under environmental conditions of low bacterial energy yield. We studied the impact of H. pylori TlpD on colonization in vivo using a gerbil infection model which closely mimics the gastric physiology of humans. A gerbil-adapted H. pylori strain, HP87 P7, showed energy-dependent behavior, while its isogenic tlpD mutant lost it. A TlpD-complemented strain regained the wild-type phenotype. Infection of gerbils with the complemented strain demonstrated that TlpD is important for persistent infection in the antrum and corpus and suggested a role of TlpD in horizontal navigation and persistent corpus colonization. As a part of the full characterization of the model and to gain insight into the genetic basis of H. pylori adaptation to the gerbil, we determined the complete genome sequences of the gerbil-adapted strain HP87 P7, two HP87 P7 tlpD mutants before and after gerbil passage, and the original human isolate, HP87. The integrity of the genome, including that of a functional cag pathogenicity island, was maintained after gerbil adaptation. Genetic and phenotypic differences between the strains were observed. Major differences between the gerbil-adapted strain and the human isolate emerged, including evidence of recent recombination. Passage of the tlpD mutant through the gerbil selected for gain-of-function variation in a fucosyltransferase gene, futC (HP0093). In conclusion, a gerbil-adapted H. pylori strain with a stable genome has helped to establish that TlpD has important functions for persistent colonization in the stomach. Helicobacter pylori chronically colonizes the gastric mucus layer of humans and induces chronic gastritis and, in severe cases, mucosa-associated lymphoid tissue lymphoma or adenocarcinoma of the stomach (1). Motility and chemotaxis are crucial features during the initiation and the persistence of H. pylori colonization, as demonstrated in vivo in mice and Mongolian gerbils (2-8). Chemotaxis allows bacteria to sense environmental stimuli and to navigate toward optimal living conditions. This is particularly important for H. pylori under the harsh conditions of the human stomach. It has been shown that H. pylori loses its motility within minutes in vivo under conditions of low pH and high pepsin activity (9). A proper orientation determined by a combination of stomach conditions/physiology and optimal bacterial tactic abilities is also required for H. pylori to reach its destination during the initial colonization process (10). Indeed, the majority of H. pylori cells detected in vivo in the Mongolian gerbil stomach were located in intimate proximity to the epithelial cells and were guided there by a vertical pH gradient in the stomach mucus (11).In H. pylori, a complete set of chemotaxis genes has been identified, including the established core genes and genes coding for four transducer-like proteins (Tlps), TlpA, TlpB, TlpC, ...

show abstract

Section: Methodsmentioning

confidence: 99%

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

et al. 2013

View full text Add to dashboard Cite

show abstract

“…7,8 Early immunological responses, which lead to precancerous gastric changes, were dependent on CagA in an animal model in vivo. 9,10 Interestingly, CagA expression alone was sufficient for the formation of gastric neoplasm even in the absence of H. pylori and without a distinct immunological response.…”

Section: Introductionmentioning

confidence: 99%

Purpose of recently detected inhibitory domain of theHelicobacter pyloriprotein CagA

Steininger

Pelz²,

Vogelmann³

2011

Gut Microbes

View full text Add to dashboard Cite

H elicobacter pylori infection is the most common bacterial infection worldwide and is strongly associated with gastric oncogenesis. Recently, we discovered that the H. pylori protein CagA, a risk factor for carcinogenesis, consists of two distinct membranetargeting domains. The C-terminal membrane-binding domain induces host cell responses associated with a high oncogenic potential. The N-terminal membrane-targeting domain, however, localizes to a different membrane substructure at the site of newly formed cellcell contacts thereby diminishing the effects of C-terminal signaling motifs on host cell physiology. This inhibitory function may allow H. pylori to establish a colonization niche in the host by maintaining the host epithelial architecture and thus decreasing the oncogenic potential as a side effect. From a bacterial standpoint, however, its main purpose maybe is to translocate the CagA protein via the type IV secretion apparatus into host epithelial cells.

show abstract

“…Studies in animal models support the epidemiological evidence that CagA is an important virulence factor for gastric cancer. In mongolian gerbils chronic infection with CagA ϩ H. pylori, but not a H. pylori mutant strain lacking CagA, causes early immunological responses, which eventually leads to precancerous gastric changes (5). Data from transgenic expression of CagA in a mouse model suggest that CagA causes the formation of gastric neoplasms even independent of chronic H. pylori infection (6,7).…”

mentioning

confidence: 99%

A Novel Inhibitory Domain of Helicobacter pylori Protein CagA Reduces CagA Effects on Host Cell Biology

Pelz

Steininger

Weiß

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

Cited by 55 publications

References 44 publications

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

Purpose of recently detected inhibitory domain of theHelicobacter pyloriprotein CagA

A Novel Inhibitory Domain of Helicobacter pylori Protein CagA Reduces CagA Effects on Host Cell Biology

Contact Info

Product

Resources

About