Helicobacter pylori virulence factors and the host immune response: implications for therapeutic vaccination

Prinz, Christian; Hafsi, Nadia; Voland, Petra

doi:10.1016/s0966-842x(03)00024-6

Cited by 52 publications

(31 citation statements)

References 47 publications

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“…Sequencing of the gene encoding this subtilase serine protease (Ssp) revealed that it contained an open reading frame encoding a 112-kDa protein. These authors found that the mature protein (41 kDa), which contains the catalytic triad (D 49 , H 85 , and S 314 ), is the middle part of a proenzyme, which starts at A 28 and finishes at D 408 . Interestingly, the secretion of the protease into the extracellular medium through the outer membrane of the E. coli host cell occurs in parallel with their growth (537).…”

Section: Sspmentioning

confidence: 99%

“…However, the exact mechanism by which H. pylori damages the human epithelial cell is not known. The bacterium expresses numerous virulence factors including the autotransporters VacA, BabA, SabA, and AlpA (201,335,408). Numerous other putative autotransporter proteins have been identified in the genome of H. pylori; however, they have not been well characterized (57).…”

Section: Clusters 2 and 11: Helicobacter Pylori Autotransportersmentioning

confidence: 99%

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Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

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Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

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Section: Sspmentioning

confidence: 99%

Section: Clusters 2 and 11: Helicobacter Pylori Autotransportersmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

View full text Add to dashboard Cite

show abstract

“…The outer membrane protein BabA (blood group antigen-binding adhesin) mediates the adherence to the ABO/Lewis b antigen in the gastric pit and is expressed by 40-95% of the H. pylori strains, also varying by geographic region [74,75]. Patients infected with a BabA-positive strain show a higher density of bacterial colonization in the stomach and enhanced inflammation due to increased IL8 levels [76].…”

Section: H Pylori Virulence Factorsmentioning

confidence: 99%

Helicobacter pylori and Gastric Cancer

Bornschein

Malfertheiner

2014

Dig Dis

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Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the ‘point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations.

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“…Immunocytologic data (expressed as 8-OHdG index) were analyzed as previously described. 22 The following equation was used for the quantitation of immunocytologic data: 8-OHdG index ¼ S[(X-threshold) Â area (mm 2 )]/total cell number, X4threshold, where X is the staining density indicated by a number between 0 and 254 on the gray scale.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…1 Many bacterial factors contribute to the development of H. pylori-related diseases, including urease-mediated acid tolerance, adherence factors necessary for colonization and maintenance of the infection, and virulence factors such as CagA and VacA that induce host cell damage. [2][3][4][5] Oxidative stress induced by reactive oxygen species (ROS) has an important role in the formation of gastric mucosal injuries by various stressors including Helicobacter infection. 6,7 There are several possible sources of ROS in Helicobacterinduced gastritis; infiltrating inflammatory cells (particularly neutrophils), gastric epithelial cells, and H. pylori itself.…”

mentioning

confidence: 99%

Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1

Kawasaki

Nishio

Nakamura

et al. 2005

Laboratory Investigation

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Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2 0 -deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1b and tumor necrosis factor-a gene expression in H. felisinfected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.

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Helicobacter pylori virulence factors and the host immune response: implications for therapeutic vaccination

Cited by 52 publications

References 47 publications

Type V Protein Secretion Pathway: the Autotransporter Story

Type V Protein Secretion Pathway: the Autotransporter Story

Helicobacter pylori and Gastric Cancer

Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1

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