• Cytotoxin-associated gene-pathogenicity island
• Gastritis
• Genetic
• Helicobacter pylori
• Proton pump inhibitors
• Transcription

• Humans
• Proton Pump Inhibitors/adverse effects
• Helicobacter pylori/genetics
• Genomic Islands/genetics
• Omeprazole/pharmacology
• Hydrogen-Ion Concentration

• Cancer progression
• Epithelial–mesenchymal transition
• Gastric cancer
• H.pylori

An ulcer is an erosion of the gastric mucosa that occurs following an imbalance between the aggression and protective factors and/or an infection with Helicobacter pylori (H. pylori). About 90-100% of duodenal ulcers and 70-80% of gastric ulcers are caused by H. pylori. The objective of this work was to evaluate in vitro the anti-H. pylori activity and then the anti-inflammatory and antioxidant properties of aqueous and methanol extracts of Alstonia boonei. The anti-H. pylori tests (CMI and antiureasic activity) were determined using the agar well diffusion method, the microbroth dilution method, and the measurement of ammonia production by the indophenol method; the anti-inflammatory properties were evaluated by inhibition of proteinases, denaturation of albumin, production of NO by macrophages, cell viability, and hemolysis of red blood cells by heat; then, the antioxidant properties were evaluated by the FRAP method (ferric reducing antioxidant power) and the DPPH (1,1-diphenyl-2-picrylhydrazyl) test. The results show that the best trapping of the DPPH radical was obtained with the methanol extract (EC₅₀ = 8.91 μg/mL) compared to the aqueous extract (EC₅₀ = 19.86 μg/mL). The methanol extract also showed greater iron-reducing activity than the aqueous extract and vitamin C. Furthermore, at the concentration of 200 μg/mL, the methanol extract showed a percentage (96.34%) strains of H. pylori higher than that of the aqueous extract (88.52%). The MIC₉₀ of the methanol extract was lower than that of the aqueous extract. The methanol extract showed a higher percentage inhibition (85%) of urease than the aqueous extract (73%). The methanol extract at a concentration of 1000 μg/mL showed the greatest ability to inhibit proteinase activity, albumin denaturation, and red blood cell hemolysis; on the other hand, maximum cell viability and greater production of nitrite oxide by macrophages were obtained with the aqueous extract. Aqueous and methanol extracts of Alstonia boonei possess anti-H. pylori which would probably be linked to their antioxidant and anti-inflammatory properties.

The utility of serum pepsinogen (sPG) I and the sPGI/II ratio as biomarkers for screening individuals with gastric cancer (GC) has not been established in Korea. The aim of this study was to define the role of sPG, especially sPGII, in GC screening.

This study enrolled 2,940 subjects, including patients with GC (n=1,124) or gastric dysplasia (n=353) and controls (n=1,463). Tests to determine sPG levels and Helicobacter pylori (HP) infection status were performed. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for sPG. The usefulness of sPG levels for the detection of GC and gastric dysplasia was validated by multivariate logistic regression.

The sPGI/II ratio was associated with the risk of gastric dysplasia and advanced-stage intestinal-type GC (IGC). In contrast, sPGII was associated with the risk of early-stage diffuse-type GC (DGC). Significantly higher risk was indicated by an sPGI/II ratio <3 for gastric dysplasia and advanced-stage IGC and by sPGII levels ≥20 µg/L for early-stage DGC. Positive HP status showed a stronger association with DGC than with IGC. When sPGII level and HP status were combined, the prevalence of DGC was higher in the ≥20 µg/L sPGII and HP-positive group. Age younger than 40 years was strongly related to early-stage DGC, especially in females (odds ratio, 21.00; p=0.006).

sPGII ≥20 ng/mL and positive HP status suggest a risk of early-stage DGC, particularly in young adult females in South Korea.

• Diffuse type
• Helicobacter pylori
• Pepsinogen
• Stomach neoplasms

• Amoxicillin
• H. pylori
• lactobionic acid
• metal organic frameworks (MOFs)

• Helicobacter
• JNK
• cancer
• cortactin
• pathogenesis
• pathogenicity island
• signalling
• virulence

• Abl
• FAK
• Helicobacter
• Src
• cancer
• cortactin
• pathogenesis
• pathogenicity island
• signaling
• virulence

• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• Focal Adhesion Kinase 1/genetics
• Gene Expression Regulation, Bacterial/genetics
• Helicobacter Infections/genetics
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions/genetics
• Humans
• Oncogene Proteins v-abl/genetics
• Phosphorylation/genetics
• src-Family Kinases/genetics

• CagL
• Helicobacter pylori
• polymorphism
• type IV secretion system

Helicobacter pylori typically colonizes the human stomach, but it can occasionally be detected in the oral cavity of infected persons. Clinical outcome as a result of gastric colonization depends on presence of the pathogenicity island cagPAI that encodes a type-IV secretion system (T4SS) for translocation of the effector protein CagA and ADP-heptose. Upon injection into target cells, CagA is phosphorylated, which can be demonstrated by in vitro infection of the gastric epithelial cell line AGS, resulting in cell elongation. Here we investigated whether H. pylori can exert these responses during interaction with cells from the oral epithelium. To this purpose, three oral epithelial cell lines, HN, CAL-27 and BHY, were infected with various virulent wild-type H. pylori strains, and CagA delivery and ADP-heptose-mediated pro-inflammatory responses were monitored.

All three oral cell lines were resistant to elongation upon infection, despite similar bacterial binding capabilities. Moreover, T4SS-dependent CagA injection was absent. Resistance to CagA delivery was shown to be due to absence of CEACAM expression in these cell lines, while these surface molecules have recently been recognized as H. pylori T4SS receptors. Lack of CEACAM expression in HN, CAL-27 and BHY cells was overcome by genetic introduction of either CEACAM1, CEACAM5, or CEACAM6, which in each of the cell lines was proven sufficient to facilitate CagA delivery and phosphorylation upon H. pylori infection to levels similar to those observed with the gastric AGS cells. Pro-inflammatory responses, as measured by interleukin-8 ELISA, were induced to high levels in each cell line and CEACAM-independent.

These results show that lack of CEACAM receptors on the surface of the oral epithelial cells was responsible for resistance to H. pylori CagA-dependent pathogenic activities, and confirms the important role for the T4SS-dependent interaction of these receptors with H. pylori in the gastric epithelium.

• AGS
• BHY
• CAL-27
• CEACAM
• CagA
• HN
• Signaling
• T4SS
• Type IV secretion
• Tyrosine kinases

• Helicobacter pylori
• Inflammasome
• Interleukin-1β
• NLRP3

• DFG-grant A04 in CRC-1181 Deutsche Forschungsgemeinschaft

Toll-like receptor TLR5 recognizes a conserved domain, termed D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Highly virulent H. pylori strains possess a type IV secretion system (T4SS) for delivery of virulence factors into gastric epithelial cells. Here, we show that one of the H. pylori T4SS components, protein CagL, can act as a flagellin-independent TLR5 activator. CagL contains a D1-like motif that mediates adherence to TLR5⁺ epithelial cells, TLR5 activation, and downstream signaling in vitro. TLR5 expression is associated with H. pylori infection and gastric lesions in human biopsies. Using Tlr5-knockout and wild-type mice, we show that TLR5 is important for efficient control of H. pylori infection. Our results indicate that CagL, by activating TLR5, may modulate immune responses to H. pylori.

Toll-like receptor TLR5 recognizes a domain, D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Here, the authors show that TLR5 can be activated independently of flagellin by a component of the H. pylori type IV secretion system that contains a D1-like motif.

Helicobacter pylori plays an essential role in the pathogenesis of gastritis, peptic ulcer disease, and gastric cancer. The serine protease HtrA, an important secreted virulence factor, disrupts the gastric epithelium, which enables H. pylori to transmigrate across the epithelium and inject the oncogenic CagA protein into host cells. The function of periplasmic HtrA for the H. pylori cell is unknown, mainly due to unavailability of the htrA mutants. In fact, htrA has been described as an essential gene in this bacterium. We have screened 100 worldwide H. pylori isolates and show that only in the N6 strain it was possible to delete htrA or mutate the htrA gene to produce proteolytically inactive HtrA. We have sequenced the wild-type and mutant chromosomes and we found that inactivation of htrA is associated with mutations in SecA – a component of the Sec translocon apparatus used to translocate proteins from the cytoplasm into the periplasm. The cooperation of SecA and HtrA has been already suggested in Streptococcus pneumonia, in which these two proteins co-localize. Hence, our results pinpointing a potential functional relationship between HtrA and the Sec translocon in H. pylori possibly indicate for the more general mechanism responsible to maintain bacterial periplasmic homeostasis.

The gastric pathogen and carcinogen Helicobacter pylori(H. pylori) encodes a type IV secretion system for translocation of the effector protein CagA into host cells. Injected CagA becomes tyrosine-phosphorylated at the five amino acid residue Glutamate-Proline- Isoleucine-Tyrosine-Alanine (EPIYA)-sequence motifs. These phosphorylated EPIYA-sites represent recognition motifs for binding of multiple host factors, which then manipulate signaling pathways to trigger gastric disease. Thus, efficient detection of single phosphorylated EPIYA-motifs in CagA is required. Detection of phospho-CagA is primarily performed using commercial pan-phosphotyrosine antibodies. However, those antibodies were originally generated to recognize many phosphotyrosines in various mammalian proteins and are not optimized for use in bacteria. To address this important limitation, we synthesized 11-mer phospho- and non-phospho-peptides from EPIYA-motifs A, B, and C, and produced three phospho-specific and three non-phospho-specific rabbit polyclonal CagA antibodies. These antibodies specifically recognized the corresponding phosphorylated and non-phosphorylated EPIYA-motifs, while the EPIYA-C antibodies also recognized the related East-Asian EPIYA-D motif. Otherwise, no cross-reactivity of the antibodies among EPIYAs was observed. Western blotting demonstrated that each EPIYA-motif can be predominantly phosphorylated during H. pylori infection. This represents the first complete set of phospho-specific antibodies for an effector protein in bacteria, providing useful tools to gather information for the categorization of CagA phosphorylation, cancer signaling, and gastric disease progression.

• Abl and Src tyrosine kinases
• CagA
• EPIYA motifs
• Helicobacter pylori
• cagPAI
• dotblot
• signaling
• type IV secretion

• Bacterial flagellum
• Bacterial motility
• Bacterial virulence
• Biosynthetic pathway
• Crystal structure
• O-linked glycosylation
• Small molecule inhibitor

• Bacterial Infections/microbiology
• Bacterial Physiological Phenomena
• Campylobacter jejuni/metabolism
• Campylobacter jejuni/pathogenicity
• Flagella/metabolism
• Flagella/physiology
• Flagellin/metabolism
• Glycosylation
• Helicobacter pylori/metabolism
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions
• Sugar Acids/metabolism

• Gastric cancer
• Helicobacter pylori
• IL-18
• IL-1β
• Inflammasome
• NOD-like receptors

• HPV genotyping
• gastric carcinoma
• high-risk HPV
• human papillomavirus

• HP0902
• Helicobacter pylori
• NMR spectroscopy
• crystal structure
• cupin superfamily
• lipopolysaccharides

The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner.

Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor κB (NF-κB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified.

Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-κB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-κB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls.

Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-κB activation and IL-8 expression in H. pylori-infected human epithelial cells.

• Helicobacter pylori
• Neutrophils
• Nod1
• Transepithelial migration
• cag pathogenicity island

HtrA proteases and chaperones exhibit important roles in periplasmic protein quality control and stress responses. The genetic inactivation of htrA has been described for many bacterial pathogens. However, in some cases such as the gastric pathogen Helicobacter pylori, HtrA is secreted where it cleaves the tumour‐suppressor E‐cadherin interfering with gastric disease development, but the generation of htrA mutants is still lacking. Here, we show that the htrA gene locus is highly conserved in worldwide strains. HtrA presence was confirmed in 992 H. pylori isolates in gastric biopsy material from infected patients. Differential RNA‐sequencing (dRNA‐seq) indicated that htrA is encoded in an operon with two subsequent genes, HP1020 and HP1021. Genetic mutagenesis and complementation studies revealed that HP1020 and HP1021, but not htrA, can be mutated. In addition, we demonstrate that suppression of HtrA proteolytic activity with a newly developed inhibitor is sufficient to effectively kill H. pylori, but not other bacteria. We show that Helicobacter  htrA is an essential bifunctional gene with crucial intracellular and extracellular functions. Thus, we describe here the first microbe in which htrA is an indispensable gene, a situation unique in the bacterial kingdom. HtrA can therefore be considered a promising new target for anti‐bacterial therapy.

The plasticity region of Helicobacter pylori (H. pylori) is a large chromosomal segment containing strain-specific genes. The prevalence of the plasticity region genes of the H. pylori strains in China remains unknown. The aim of this study was to examine the status of these genes and to assess the relationship between the genes and the diseases caused by H. pylori infection.

A total of 141 strains were isolated from patients with chronic active gastritis (CAG), peptic ulcer disease (PUD) and gastric carcinoma (GC). The prevalence of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 was determined using PCR, and the results were analyzed using the chi-squared test.

The prevalence rates of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 in the H. pylori strains were 42.55, 51.06, 20.57, 56.03 and 63.12 %, respectively. The prevalence rates of jhp0940 were similar in the isolates from the CAG, PUD and GC patients, and there was no association between the jhp0940 status and any of the diseases. In contrast, the prevalence rates of jhp0945, jhp0947, jhp0949 and jhp0951 were significantly higher in the PUD and GC isolates than in the CAG isolates (p < 0.01). A univariate analysis showed that jhp0945, jhp0947, jhp0949 and jhp0951 increased the risk of PUD, while only jhp0951 was significantly associated with PUD in the multivariate analysis (p = 0.0149). The jhp0945-positive isolates were significantly associated with an increased risk for GC (p = 0.0097).

The plasticity region genes are widely distributed in Chinese patients, and a high prevalence of these genes occurs in more serious diseases. Therefore, jhp0951 status is an independent factor associated with the development of PUD, and jhp0945 may predict the future development of GC in patients with CAG and is considered to be the best candidate disease marker for H. pylori-related diseases.

• Cag PAI
• DupA
• H. pylori
• OMPs
• VacA
• gastric carcinoma
• virulence factors

• comparative genomics
• core genome
• endophyte
• niche occupation
• synteny
• virulence

Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen.

• Antigens, Bacterial/physiology
• Bacterial Proteins/genetics
• Bacterial Proteins/physiology
• Cell Line
• Genes, Bacterial
• Helicobacter Infections/etiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Helicobacter pylori/physiology
• Host-Pathogen Interactions/genetics
• Host-Pathogen Interactions/physiology
• Humans
• Interleukin-8/biosynthesis
• Mutation
• Phenotype
• Type IV Secretion Systems/genetics
• Type IV Secretion Systems/physiology
• Urease/metabolism
• Virulence/genetics
• Virulence/physiology
• Virulence Factors/genetics
• Virulence Factors/physiology

• Amino Acid Motifs
• Amino Acid Sequence
• Antigens, Bacterial/metabolism
• Bacterial Proteins/metabolism
• Cell Line, Tumor
• Gastric Mucosa/metabolism
• Helicobacter Infections/metabolism
• Helicobacter pylori/metabolism
• Humans
• Molecular Sequence Data
• Phosphorylation/physiology
• Phosphotyrosine/metabolism
• Sequence Alignment

• R01DK62813 NIDDK NIH HHS
• R21 AI078237 NIAID NIH HHS
• R21 AI088337 NIAID NIH HHS
• P30 DK056338 NIDDK NIH HHS
• R01 DK062813 NIDDK NIH HHS

• Aged
• Antibodies, Bacterial/blood
• Antigens, Bacterial/immunology
• Bacterial Proteins/immunology
• Biomarkers/analysis
• Chronic Disease
• Cross-Sectional Studies
• Dyspepsia/complications
• Female
• Follow-Up Studies
• Gastrins/blood
• Gastritis/blood
• Gastritis/diagnosis
• Gastritis/etiology
• Helicobacter Infections/immunology
• Helicobacter pylori/immunology
• Humans
• Iran
• Male
• Pepsinogen A/blood
• Pepsinogen C/blood
• Precancerous Conditions/blood
• Precancerous Conditions/diagnosis
• Precancerous Conditions/etiology
• Prognosis
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/etiology

• Helicobacter pylori
• cag pathogenicity-island
• gastritis
• peptic ulcer
• polymerase chain reaction

• DNA, Bacterial/genetics
• Dyspepsia/microbiology
• Dyspepsia/pathology
• Genetic Variation
• Genomic Islands
• Genotype
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Humans
• Polymerase Chain Reaction
• Treatment Outcome
• Turkey
• Virulence Factors/genetics

The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA)-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation - a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.

• Amino Acid Sequence
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/metabolism
• Bacterial Proteins/chemistry
• Bacterial Proteins/metabolism
• Crystallography, X-Ray
• Models, Molecular
• Molecular Sequence Data
• Protein Denaturation
• Protein Multimerization
• Protein Stability
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Proteolysis
• Repetitive Sequences, Amino Acid
• Temperature

• Animals
• Apoptosis
• Bacterial Proteins/immunology
• Bacterial Proteins/metabolism
• Gene Expression
• HEK293 Cells
• Helicobacter pylori/immunology
• Helicobacter pylori/metabolism
• Humans
• Lipopolysaccharides/pharmacology
• MAP Kinase Signaling System
• Macrophages/physiology
• Mice
• NF-kappa B/metabolism
• Phosphorylation
• Protein Binding
• Protein Processing, Post-Translational
• Transcription Factor AP-1/metabolism
• Transcriptional Activation
• Tumor Necrosis Factor-alpha/physiology

Gastric mucosa tissue was collected from patients with gastroduodenal diseases in a region of norrteastern China showing a high risk of gastric cancer incidence. The presence of EBV and HPV were assayed to investigate the relationship between gastric carcinomas and virus infection. Neither EBV nor HPV DNA was detected in tissue from the patients. The role of EBV and HPV in gastric cancer is not well understood and still needs to be clarified.

• Epstein-Barr virus
• Human papillomavirus
• gastric carcinoma
• polymerase chain reaction

• DNA, Bacterial/chemistry
• DNA, Bacterial/genetics
• Genotype
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Humans
• Peptic Ulcer/microbiology
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology
• Virulence Factors/genetics

• CagA protein
• Cell elongation
• Glu-Pro-Ile-Tyr-Ala
• Helicobacter pylori
• Interleukin 8
• cagA 3’ region

• CagA
• CagL
• Helicobacter pylori
• T4SS

In this study, a whole-genome CombiMatrix Custom oligonucleotide tiling microarray with 90000 probes covering six sequenced Helicobacter pylori (H. pylori) genomes was designed. This microarray was used to compare the genomic profiles of eight unsequenced strains isolated from patients with different gastroduodenal diseases in Heilongjiang province of China. Since significant genomic variation was found among these strains, an additional 76 H. pylori strains associated with different clinical outcomes were isolated from various provinces of China. These strains were tested by polymerase chain reaction to demonstrate this distinction. We identified several highly variable regions in strains associated with gastritis, gastric ulceration, and gastric cancer. These regions are associated with genes involved in the bacterial type I, type II, and type III R-M systems. They were also associated with the virB gene, which lies on the well-studied cag pathogenic island. While previous studies have reported on the diverse genetic characterization of this pathogenic island, in this study, we find that it is conserved in all strains tested by microarray. Moreover, a number of genes involved in the type IV secretion system, which is related to horizontal DNA transfer between H. pylori strains, were identified in the comparative analysis of the strain-specific genes. These findings may provide insight into new biomarkers for the prediction of gastric diseases.

• China
• Genetic Variation
• Genome, Bacterial/genetics
• Genomic Islands/genetics
• Helicobacter Infections/genetics
• Helicobacter pylori/genetics
• Humans
• Oligonucleotide Array Sequence Analysis
• Species Specificity
• Stomach Diseases/microbiology

• Amino Acid Motifs
• Amino Acid Sequence
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/genetics
• Antigens, Bacterial/metabolism
• Bacterial Proteins/chemistry
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• CSK Tyrosine-Protein Kinase
• Cell Line/microbiology
• Europe/epidemiology
• Asia, Eastern/epidemiology
• Helicobacter Infections/ethnology
• Helicobacter Infections/microbiology
• Helicobacter pylori/classification
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Helicobacter pylori/metabolism
• Host-Pathogen Interactions
• Humans
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Phosphorylation
• Phosphotyrosine/metabolism
• Protein Processing, Post-Translational
• Protein-Tyrosine Kinases/metabolism
• Proto-Oncogene Proteins c-abl/metabolism
• Recombinant Proteins/metabolism
• Sequence Alignment
• Sequence Homology, Amino Acid
• src-Family Kinases

• R01DK62813 NIDDK NIH HHS
• R56DK064371 NIDDK NIH HHS
• P 24315 Austrian Science Fund FWF
• R56 DK064371 NIDDK NIH HHS
• R01 DK062813 NIDDK NIH HHS

• Animals
• Antibodies, Viral/pharmacology
• Cell Line/virology
• Cell Shape/drug effects
• Helicobacter pylori/physiology
• Humans
• Inclusion Bodies, Viral/metabolism
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Microscopy, Immunoelectron
• Parainfluenza Virus 5/immunology
• Parainfluenza Virus 5/pathogenicity
• Parainfluenza Virus 5/ultrastructure
• Rabbits
• Rubulavirus Infections/transmission
• Rubulavirus Infections/virology
• Virion/immunology
• Virion/pathogenicity
• Virion/ultrastructure

• Amino Acid Sequence
• Apoptosis
• Bacterial Proteins/chemistry
• Bacterial Proteins/metabolism
• Gastrointestinal Diseases/metabolism
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Diseases/pathology
• Genetic Loci/genetics
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/isolation & purification
• Helicobacter pylori/metabolism
• Humans
• Immunity, Humoral
• Inflammation Mediators/metabolism
• Interleukin-8/metabolism
• Models, Biological
• Molecular Sequence Data
• NF-kappa B/metabolism
• Protein Binding
• Receptors, Tumor Necrosis Factor, Type I/metabolism
• Recombinant Proteins/isolation & purification
• Recombinant Proteins/metabolism
• Sequence Alignment
• Sequence Analysis, Protein
• Time Factors
• Tumor Necrosis Factor-alpha/metabolism
• fas Receptor/metabolism

AIM: To investigate the effect of H. pylori extract on cellular morphology and apoptosis-related gene expression in human gastric cancer BGC-823 cells.

METHODS: After BGC-823 cells were treated with ultrasonic extract of the east Asia type or the Western type of H. pylori strain, the changes in cellular morphology were observed by microscopy, and the expression of survivin and caspase-3 mRNAs was detected by fluorescent quantitative polymerase chain reaction (QRT-PCR). The possible correlation between the expression of survivin mRNA and that of caspase-3 mRNA was also analyzed.

RESULTS: Hummingbird phenotype was observed in BGC-823 cells 12 h after stimulation H. pylori extract, which was most obvious at 24 h. The percentage of cells showing hummingbird phenotype was significantly higher in cells treated with the extract of the east Asia type than in those treated with the extract of the Western type (29.3 ± 2.1 vs 8.0 ± 2.0, F = 164.73, P < 0.05). The expression of survivin mRNA was significantly higher and that of caspase-3 mRNA was significantly lower in BGC-823 cells treated with H. pylori extract than in control cells (both P < 0.05). Statistical difference was also noted in the expression of survivin and caspase-3 mRNAs between cells treated with the extract of the east Asia type group and those with the extract of the Western type group.

CONCLUSION: H. pylori extract could induce changes in cellular morphology and expression of survivin and caspase-3 mRNAs in human gastric cancer BGC-823 cells. The extract of the east Asia type of H. pylori has more potent biological activity than that of the Western type.

• H. pylori
• Hummingbird phenotype
• Apoptosis-related genes
• CagA typing