Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E‐cadherin to disrupt intercellular adhesion

Mammalian and prokaryotic high‐temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of the cell‐adhesion protein E‐cadherin. E‐cadherin shedding disrupts epithelial barrier functions allowing H. pylori designed to access the intercellular space. We then designed a small‐molecule inhibitor that efficiently blocks HtrA activity, E‐cadherin cleavage and intercellular entry of H. pylori.     

Food-Grade Expression of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> UreB Subunit in <Emphasis Type="Italic">Lactococcus lactis</Emphasis> and its Immunoreactivity

Helicobacter pylori is the principal cause of chronic active gastritis, peptic ulcer, and gastric cancer. To develop an oral vaccine against H. pylori infection, we had expressed the H. pylori ureB gene (Genbank accession no. FJ436980) in nisin-controlled expression vectors using Lactococcus lactis NZ3900 as host. The ureB gene was amplified by PCR from a H.pylori strain MEL-Hp27. Then the ureB gene was fused translationally downstream of the nisin-inducible promoter nisA in a L. lactis plasmid pNZ8149. Lactose utilization based on the complementation of the lacF gene was used as a dominant selection marker for the food-grade expression system employing L. lactis NZ3900. The conditions of UreB expression in this system were optimized by orthogonal experiment. The optimized conditions have been determined as follows: induction of expression was carried out at the cells density of OD₆₀₀ ≈ 0.4 with 25 ng/ml nisin, and harvest after 5 h. The maximum percentage of recombinant UreB was estimated to be 7% of total soluble cellular proteins and the yield was 12.9 μg/ml. Western blot demonstrated that the UreB protein was expressed in the L. lactis transformant and had favorable immunoreactivity. These results indicated that the lactococci-derived vaccines could be promising candidates as alternative vaccine strategies for preventing H. pylori infection.     

A Thin‐Layer Liquid Culture Technique for the Growth of Helicobacter pylori

Background and Aims: Several attempts have been successful in liquid cultivation of Helicobaccter pylori. However, there is a need to improve the growth of H. pylori in liquid media in order to get affluent growth and a simple approach for examining bacterial properties. We introduce here a thin‐layer liquid culture technique for the growth of H. pylori. Methods: A thin‐layer liquid culture system was established by adding liquid media to a 90‐mm diameter Petri dish. Optimal conditions for bacterial growth were investigated and then viability, growth curve, and released proteins were examined. Results: Maximal growth of H. pylori was obtained by adding 3 mL of brucella broth supplemented with 10% horse to a Petri dish. H. pylori grew in both DMEM and RPMI‐1640 supplemented with 10% fetal bovine serum and 0.5% yeast extract. Serum‐free RPMI‐1640 supported the growth of H. pylori when supplemented with dimethyl‐β‐cyclodextrin (200 μg/mL) and 1% yeast extract. Under optimal growth, H. pylori grew exponentially for 28 hours, reaching a density of 3.4 OD₆₀₀ with a generation time of 3.3 hours. After 24 hours, cultures at a cell density of 1.0 OD₆₀₀ contained 1.3 ± 0.1 × 10⁹ CFU/mL. γ‐Glutamyl transpeptidase, nuclease, superoxide dismutase, and urease were not detected in culture supernatants at 24 hours in thin‐layer liquid culture, but were present at 48 hours, whereas alcohol dehydrogenase, alkylhydroperoxide reductase, catalase, and vacuolating cytotoxin were detected at 24 hours. Conclusions: Thin‐layer liquid culture technique is feasible, and can serve as a versatile liquid culture technique for investigating bacterial properties of H. pylori.     

Helicobacter pylori Infection – A Boon or a Bane: Lessons from Studies in a Low‐Prevalence Population

Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori‐infected non‐Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.     

Cholesterol glucosylation–based survival strategy in Helicobacter pylori

Helicobacter pylori is a major chronic health problem, infecting more than half of the population worldwide. H. pylori infection is linked with various clinical complications ranging from gastritis to gastric cancer. The resolution of gastritis and peptic ulcer appears to be linked with the eradication of H. pylori. However, resistance to antibiotics and eradication failure rates are reaching alarmingly high levels. This calls for urgent action in finding alternate methods for H. pylori eradication. Here, we discuss the recently identified mechanism of H. pylori known as cholesterol glucosylation, mediated by the enzyme cholesterol-α-glucosyltransferase, encoded by the gene cgt. Cholesterol glucosylation serves several functions that include promoting immune evasion, enhancing antibiotic resistance, maintaining the native helical morphology, and supporting functions of prominent virulence factors such as CagA and VacA. Consequently, strategies aiming at inhibition of the cholesterol glucosylation process have the potential to attenuate the potency of H. pylori infection and abrogate H. pylori immune evasion capabilities. Knockout of H. pylori cgt results in unsuccessful colonization and elimination by the host immune responses. Moreover, blocking cholesterol glucosylation can reverse antibiotic susceptibility in H. pylori. In this work, we review the main roles of cholesterol glucosylation in H. pylori and evaluate whether this mechanism can be targeted for the development of alternate methods for eradication of H. pylori infection.     

Comparative Evaluation of Three Supplements for Helicobacter pylori Growth in Liquid Culture

Helicobacter pylori, a microaerophilic fastidious bacterium, has been cultured on various plating and broth media since its discovery. Although the agar media can be sufficient for the identification, typing, and antibiotic resistance studies, no secretory antigen of H. pylori can be evaluated in such media. Thus, satisfactory growth of H. pylori in liquid culture which is needed for analysis of secretory proteins without the presence of interfering agents is in demand. We assessed the impact of β-cyclodextrin, Fetal Bovine Serum (FBS), and charcoal as supplements for H. pylori growth. Furthermore, we aimed to identify the most favorable supplement that supports the secretion of the dominant secretory protein, vacuolating cytotoxin (VacA). Five clinical strains were cultured on broth media and the growth, viability, morphology, and protein content of each strain were determined. Our results revealed that β-cyclodextrin supports the growth rate, viability, and cell lysate protein content to the extent similar to FBS. Application of β-cyclodextrin is found to postpone spiral to coccoid conversion up to 72 h of incubation. Although FBS supports a higher VacA protein content, presence of interfering macromolecules in FBS questions its utility particularly for purposes of studying extra cellular proteins such as VacA. This study recommends further application of β-cyclodextrin as a culture supplement with the potential capacity in neutralizing toxic compounds and flourishing the secretion of H. pylori proteins without addition of interfering proteins.     

H. pylori predictors and outcomes among adults undergoing upper endoscopy at a Jamaican teaching hospital: A cross-sectional study

Background

Recent data on the prevalence of H. pylori infection in Jamaica are lacking. It is postulated that there has been a decline in the prevalence of H. pylori infection and its associated complications. We determined sociodemographic characteristics, prevalence of H. pylori infection and clinical outcomes among adults undergoing esophagogastroduodenoscopy (EGD) and histology at the University Hospital of the West Indies (UHWI) between May 2018 and December 2020.

Materials and methods

A cross-sectional study of patients (≥18 years old), who underwent EGD and histological evaluation for H. pylori infection, was conducted. Associations of H. pylori positivity and gastric cancer with sociodemographic/clinical variables and endoscopic findings were determined by stepwise logistic regression using backward selection. Unadjusted and adjusted odds ratios with related 95% confidence intervals (Cis) were calculated for H. pylori positivity and gastric cancer status.

Results

There were 323 participants (mean age 58.6 ± 17.8 years, 54.2% females). H. pylori prevalence was 22.2% (n = 70 of 315), 5.6% had gastric neoplasia (GN), 15.5% gastric atrophy, 11.4% intestinal metaplasia and 3.7% dysplasia on histology. Mucositis (64.5%), gastric ulcer (14.9%), and duodenal ulcer (13.9%) were the most common endoscopic findings. Participants with peptic ulcer disease (PUD) (unOR = 4.0; p = .017), gastric cancer (unOR = 9.5; p = .003), gastric atrophy (unOR = 12.8; p < .001), and intestinal metaplasia (unOR = 5.0; p < .001) had a significantly higher odds of being H. pylori positive, but after multivariable analyses only gastric atrophy remained significant (aOR = 27.3; p < .001). Participants with mucositis had a significantly lower odds of gastric cancer (unOR 0.1; p = .035) while participants with dysplasia had significantly higher odds (unOR 8.0; p = .042), but these were no longer significant after multivariable analyses (aOR = 0.2; p = .156 and aOR = 18.9; p = .070, respectively).

Conclusions

Histology based prevalence of H. pylori infection is lower than previously reported in Jamaica. Gastric atrophy is a significant predictor of H. pylori positivity.     

Helicobacter pylori-downregulated tumor necrosis factor receptor-associated protein 1 mediates apoptosis of human gastric epithelial cells

Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real-time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin-associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real-time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis.     

Characterization of Helicobacter pylori HP0231 (DsbK): role in disulfide bond formation,redox homeostasis and production of Helicobacter cystein‐rich protein HcpE

Helicobacter pylori is a human gastric pathogen that colonizes ～ 50% of the world's population. It can cause gastritis, gastric or duodenal ulcers and also gastric cancer. The numerous side effects of available treatments and the emergence of antibiotic resistant strains are severe concerns that justify further research into H. pylori's pathogenic mechanisms. H. pylori produces secreted proteins that may play a role in virulence, including the Helicobacter cysteine‐rich protein HcpE (aka HP0235). We demonstrate herein that HcpE is secreted in the culture supernatant both as a soluble protein and in association with outer membrane vesicles. We show that the structure of HcpE comprises an organized array of disulfide bonds. We identify DsbK (aka HP0231) as a folding factor necessary for HcpE production and secretion in H. pylori and show that recombinant DsbK can interact with and refold unprocessed, reduced HcpE in vitro. These experiments highlight the first biologically relevant substrate for DsbK. Furthermore, we show that DsbK has disulfide bond (Dsb) forming activity on reduced lysozyme and demonstrate a DsbA‐type of activity for DsbK upon expression in E. coli, despite its similarity with DsbG. Finally, we show a role of DsbK in maintaining redox homeostasis in H. pylori.     

Protein changes in gastric epithelial cells RGM-1 in response to Helicobacter pylori infection

Helicobacter pylori-induced inflammation significantly increases the risk of gastric cancer. To investigate the role of H. pylori infection in gastric epithelial cell carcinogenesis, flow cytometry was used to analyze the apoptosis of gastric epithelial cells infected by H. pylori. Next, LTQ MS mass spectrometry (MS) was applied to identify protein changes in gastric epithelial cells infected with H. pylori, and then bioinformatics was adopted to analyze the cellular localization and biological function of differential proteins. LTQ MS/MS successfully identified identified 22 differential proteins successfully, including 20 host-cell proteins and two H. pylori bacterial proteins. Also, human proteins were located in all areas of cells and involved in various cell biological functions. The oncogene proteins p53, p16, and C-erbB-2 proteins in H. pylori-infected RGM-1 cells were remarkably increased from the analysis by Western blot analysis. H. pylori infection of gastric epithelial cells leads to changes in various protein components in the cell, and enhances the expression of oncogene proteins, thereby increasing the possibility of possibility of carcinogenesis of H. pylori infection.     

Functional characterization of Helicobacter pylori TlyA: Pore-forming hemolytic activity and cytotoxic property of the protein

Helicobacter pylori is a human specific gastric pathogen. H. pylori pathogenesis process involves a number of well-studied virulence factors that include the ‘vacuolating cytotoxin’ and the ‘cytotoxin associated gene A’. Analysis of the H. pylori genome, however, indicates presence of additional virulence factors that are yet to be characterized in molecular detail. For example, H. pylori genome harbors a gene that has potential to encode a protein with sequence similarity to those of the TlyA-like proteins of several pathogenic bacteria. Earlier studies have indicated potential association of this H. pylori tlyA gene in the virulence mechanism of the organism. Despite such notions, however, the TlyA-like protein of H. pylori has not been studied previously in molecular detail. In particular, purified form of H. pylori TlyA has never been studied before toward exploring its functional properties. Here, we report characterization of the H. pylori TlyA protein purified from the recombinant over-expression system in Escherichia coli. Purified form of the recombinant TlyA exhibits prominent hemolytic activity against human erythrocytes, presumably via formation of pores of specific diameter in the cell membrane. Purified TlyA also triggers prominent cytotoxic responses in human gastric adenocarcinoma cells. Altogether, our study establishes H. pylori TlyA as a potential virulence factor of the organism.     

Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA

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.     

UreB immunodominant epitope-specific CD8+ T-cell responses were beneficial in reducing gastric symptoms in Helicobacter pylori-infected individuals

Background and aims

Although Helicobacter pylori is recognized as an extracellular infection bacterium, it can lead to an increase in the number of CD8⁺ T cells after infection. At present, the characteristics of H. pylori antigen-specific CD8⁺ T cells and the epitope response have not been elucidated. This study was focused on putative protective antigen UreB to detect specific CD8⁺ T-cell responses in vitro and screen for predominant response epitopes.

Methods

The PBMCs collected from H. pylori-infected individuals were stimulated by UreB peptide pools in vitro to identify the immunodominant CD8⁺ T-cell epitopes. Furthermore, their HLA restriction characteristics were detected accordingly by NGS. Finally, the relationship between immunodominant responses and appearance of gastric symptoms after H. pylori infection was conducted.

Results

UreB-specific CD8⁺ T-cell responses were detected in H. pylori-infected individuals. Three of UreB dominant epitopes (A-2 (UreB_443–451: GVKPNMIIK), B-4 (UreB_420–428: SEYVGSVEV), and C-1 (UreB_5–13: SRKEYVSMY)) were firstly identified and mainly presented by HLA-A*1101, HLA-B*4001 and HLA-C*0702 alleles, respectively. C-1 responses were mostly occurred in H. pylori-infected subjects without gastric symptoms and may alleviate the degree of gastric inflammation.

Conclusions

The UreB dominant epitope-specific CD8⁺ T-cell response was closely related to the gastric symptoms after H. pylori infection, and the C-1 (UreB_5-13) dominant peptides may be protective epitopes.     

The Hsp60 protein of Helicobacter pylori: structure and immune response in patients with gastroduodenal diseases

Helicobacter pylori is a human pathogen that has been associated with gastritis, peptic ulcer and gastric carcinoma. The role of the direct action of H. pylori virulence factors and of the induction of autoreactive immunity in the development of chronic gastritis has not been clarified yet. Here we report the cloning and molecular characterization of a gene of H. pylori coding for a protein of 58kDa, recognized by sera of patients affected by H. pylori-induced gastroduodenal diseases. This antigen is present in all the H. pylori strains tested and it belongs to the Hsp60 family of heat-shock proteins, with high homology with other bacterial and eukaryotic proteins of the same family. This class of homologous proteins has been implicated in the induction of autoimmune disorders in different systems. The presence in infected patients of anti-H. pylori Hsp60 antibodies, potentially cross-reacting with the human homologue, and cross-reactivity between human Hsp60 and a rabbit antiserum against H. pylori Hsp60 suggest that a role of this protein in gastroduodenal diseases is possible.     

H. pylori‐Induced Apoptosis in Human Gastric Cancer Cells Mediated via the Release of Apoptosis‐Inducing Factor from Mitochondria

Background and Aim: Our previous study of Helicobacter pylori‐induced apoptosis showed the involvement of Bcl‐2 family proteins and cytochrome c release from mitochondria. Here, we examine the release of other factors from mitochondria, such as apoptosis‐inducing factor (AIF), and upstream events involving caspase‐8 and Bid. Methods: Human gastric adenocarcinoma (AGS) cells were incubated with a cagA‐positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected. Results: Proteins were immunoblotted for AIF, Bid, polyadenosine ribose polymerase (PARP), caspase‐8, and β‐catenin. H. pylori activated caspase‐8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time‐dependent decrease in β‐catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with a decrease in β‐actin. An increase in the cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band corresponding to full‐length Bid was seen in both the cytoplasmic and the nuclear fractions of controls, but not after H. pylori exposure. Active AIF staining was markedly increased in gastric mucosa from infected persons, compared to uninfected controls. Conclusion: H. pylori might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase‐8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin. This is consistent with AIF activation that was found in the gastric mucosa of humans infected with H. pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer.     

Anti‐Helicobacter pylori therapy in localized gastric mucosa‐associated lymphoid tissue lymphoma: A prospective,nationwide, multicenter study in Japan

Background

Helicobacter pylori eradication therapy was approved in Japan for the first‐line, standard treatment of H. pylori‐positive gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small‐scale single‐center studies have been reported, a prospective, large‐scale, nationwide, multicenter study has not been reported from Japan.

Materials and Methods

We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole‐based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice‐based clinical trial. A total of 108 H. pylori‐positive patients with stage I/II₁ gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS).

Results

CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0‐44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4‐53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow‐up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma.

Conclusions

Rabeprazole‐based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice‐based, multicenter study.     

Helicobacter pylori Infection and Recurrent Abdominal Pain in Turkish Children

Background. Helicobacter pylori infection is primarily acquired in childhood. However, the association between H. pylori infection and recurrent abdominal pain (RAP) remains unclear. Materials and methods. One hundred and forty-one children with and 21 without RAP underwent upper gastrointestinal endoscopy. At least five antral gastric biopsies were obtained from each patient and the presence of H. pylori infection was accepted when at least two out of four tests (histology, direct antral smear, culture, and rapid urease test) were positive. Patients with H. pylori infection underwent triple therapy with omeprazole, clarithromycin, and metronidazole. Results. Eighty-five out of 141 (60.3%) patients with RAP were H. pylori positive whereas 5 out of 21 (20.8%) patients without RAP were (p = .0037). Symptoms were disappeared in 87% of children whose H. pylori infection was eradicated compared with 41% of those in whom the infection was not eradicated (p = .0035). Conclusions. It was concluded that children with RAP and H. pylori infection appear to benefit from eradication therapy in Turkey.     

Interleukin-8 is the single most up-regulated gene in whole genome profiling of <Emphasis Type="Italic">H. pylori</Emphasis> exposed gastric epithelial cells

Background  

The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA^- H. pylori variants.     

Review: Pathogenesis of Helicobacter pylori infection

In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins.