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SUMMARYThe majority of the world population carry the gastric pathogenHelicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism whereH. pyloriattachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority ofH. pyloricarriers. These antibodies block binding of theH. pyloriattachment protein BabA by mimicking BabA’s binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

Non-typhoidal Salmonella serotypes are well adapted to utilize the inflammation for colonization in the mammalian gut mucosa and cause loss of the integrity of the epithelial barrier in the mammalian intestine.

Helicobacter pylori a key agent for causing gastric complications is linked with peptic ulcer, gastritis, and in severe cases gastric cancer. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the host’s autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented in gastric cancer and many other cancers. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. Human gastric cancer (AGS) cells were infected with H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression levels of autophagy proteins. Autophagy and lysosomal activity were monitored by immunofluorescence. We have performed knockdown of HMGB1 to verify the effect of glycyrrhizin by siRNA transfection method. H. pylori-infection in vivo C56BL/6 mice model was established and the effect of glycyrrhizin treatment was studied. We found that the autophagy-lysosomal pathway was impaired due to a significant increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity, accompanied by an increase in cathepsin B activity and reduction of ROS and inflammatory cytokine IL-8. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche from gastric cells. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damages in mice.

Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative, human gastric pathogen found usually in the mucous lining of stomach. It infects more than 50% of the world’s population and leads to gastroduodenal diseases. The outcome of disease depends on mainly three factors: Host genetics, environment and bacterial factors. Among these, bacterial virulence factors such as cagA, vacA are well known for their role in disease outcomes. However, based on the global epidemiological results, none of the bacterial virulence (gene) factors was found to be associated with particular diseases like duodenal ulcer (DU) in all populations. Hence, substantial importance has been provided for research in strain-specific genes outside the cag pathogenicity island, especially genes located within the plasticity regions. dupA found within the plasticity regions was first demonstrated in 2005 and was proposed for duodenal ulcer development and reduced risk of gastric cancer in certain geographical regions. Due to the discrepancies in report from different parts of the world in DU development related to H. pylori virulence factor, dupA became an interesting area of research in elucidating the role of this gene in the disease progression. In this review, we shed light on the detailed information available on the polymorphisms in dupA and their clinical relevance. We have critically appraised several pertinent studies on dupA and discussed their merits and shortcomings. This review also highlights dupA gene as an important biomarker for DU in certain populations.

Helicobacter pylori is a ubiquitous bacterium and contributes significantly to the burden of chronic gastritis, peptic ulcers, and gastric cancer across the world. Adaptive phenotypes and virulence factors in H. pylori are heterogeneous and dynamic. However, limited information is available about the molecular nature of antimicrobial resistance phenotypes and virulence factors of H. pylori strains circulating in India. In the present study, we analyzed the whole genome sequences of 143 H. pylori strains, of which 32 are isolated from two different regions (eastern and southern) of India. Genomic repertoires of individual strains show distinct region-specific signatures. We observed lower resistance phenotypes and genotypes in the East Indian (Kolkata) H. pylori isolates against amoxicillin and furazolidone antibiotics, whereas higher resistance phenotypes to metronidazole and clarithromycin. Also, at molecular level, a greater number of AMR genes were observed in the east Indian H. pylori isolates as compared to the southern Indian isolates. From our findings, we suggest that metronidazole and clarithromycin antibiotics should be used judicially in the eastern India. However, no horizontally acquired antimicrobial resistance gene was observed in the current H. pylori strains. The comparative genome analysis shows that the number of genes involved in virulence, disease and resistance of H. pylori isolated from two different regions of India is significantly different. Single-nucleotide polymorphisms (SNPs) based phylogenetic analysis distinguished H. pylori strains into different clades according to their geographical locations. Conditionally beneficial functions including antibiotic resistance phenotypes that are linked with faster evolution rates in the Indian isolates.

Helicobacter pylori (H. pylori) is known to cause several gastroduodenal diseases including chronic Gastritis, Peptic Ulcer disease and Gastric Cancer. Virulent genes of H. pylori like cagA, vacA are known to be responsible for the disease pathogenesis. However, these virulence genes are not always found to be associated with disease outcome in all populations around the world. Tumor necrosis factor alpha inducing protein tipα is a newly discovered virulence gene of H. pylori and is an inducer of certain cytokines and chemokines that are responsible for causing stomach cancer. Therefore, we conducted a study, which aims to find the prevalence of tipα gene in the Indian patients with gastroduodenal symptoms, and its association with H. pylori related gastroduodenal diseases. 267 clinical H. pylori isolates are included in our study for finding the prevalence of tipα gene and its association with cagA and vacA gene using PCR assay. The current study shows that the prevalence rate of tipα gene is 59.9%. Our study has found a significant association (p

Infection with Helicobacter pylori (H. pylori) is of great distress because of its vital role in the pathogenesis of chronic gastritis, peptic ulcers, and in the multi-step carcinogenic process of gastric cancer. The increasing antibiotic resistance pattern of H. pylori worldwide has prompted the World Health Organization to put this organism in the priority pathogens list. To study the disease biology, evaluation of drugs, treatment outcome and to come up with probable vaccination strategies, competent animal models that reproduce the signature of human infection are essential. Initial reports about animal colonization with H. pylori have shown significant heterogeneity, to such an extent that Barry Marshall, Nobel laureate for the discovery of H. pylori , infected himself with the bacterium to show its involvement in acute gastric illness. A paradigm-shift discovery of the H. pylori mouse-adapted strain SS1 has opened the avenues of research regarding the organism and its pathogenicity. Although the mouse model of H. pylori infection is being utilized all over the world, there are certain issues that need awareness and specific information to achieve successful, consistent colonization with symptoms resembling human. This chapter details an established and reliable protocol for the development of a competent mouse model for H. pylori infection leading to various gastro-intestinal diseases.

Helicobacter pylori (H. pylori) is known to cause several gastroduodenal diseases including chronic Gastritis, Peptic Ulcer disease and Gastric Cancer. Virulent genes of H. pylori like cagA, vacA are known to be responsible for the disease pathogenesis. However, these virulence genes are not always found to be associated with disease outcome in all populations around the world. Tumor necrosis factor alpha inducing protein tipα is a newly discovered virulence gene of H. pylori and is an inducer of certain cytokines and chemokines that are responsible for causing stomach cancer. Therefore, we conducted a study, which aims to find the prevalence of tipα gene in the Indian patients with gastroduodenal symptoms, and its association with H. pylori related gastroduodenal diseases. 267 clinical H. pylori isolates are included in our study for finding the prevalence of tipα gene and its association with cagA and vacA gene using PCR assay. The current study shows that the prevalence rate of tipα gene is 59.9%. Our study has found a significant association (p

Infection with Helicobacter pylori (H. pylori) is of great distress because of its vital role in the pathogenesis of chronic gastritis, peptic ulcers, and in the multi-step carcinogenic process of gastric cancer. The increasing antibiotic resistance pattern of H. pylori worldwide has prompted the World Health Organization to put this organism in the priority pathogens list. To study the disease biology, evaluation of drugs, treatment outcome and to come up with probable vaccination strategies, competent animal models that reproduce the signature of human infection are essential. Initial reports about animal colonization with H. pylori have shown significant heterogeneity, to such an extent that Barry Marshall, Nobel laureate for the discovery of H. pylori , infected himself with the bacterium to show its involvement in acute gastric illness. A paradigm-shift discovery of the H. pylori mouse-adapted strain SS1 has opened the avenues of research regarding the organism and its pathogenicity. Although the mouse model of H. pylori infection is being utilized all over the world, there are certain issues that need awareness and specific information to achieve successful, consistent colonization with symptoms resembling human. This chapter details an established and reliable protocol for the development of a competent mouse model for H. pylori infection leading to various gastro-intestinal diseases.

Helicobacter pylori, a type 1 carcinogen, accounts for numerous gastric cancer-related deaths worldwide. Repurposing existing drugs or developing new ones for a combinatorial approach against increasing antimicrobial resistance is the need of the hour. This study highlights the efficacy of acriflavine hydrochloride (ACF-HCl) in inhibiting the growth of H. pylori reference strain and antibiotic-resistant clinical isolates at low concentrations. ACF-HCl inhibits H. pylori growth at MIC value 10 times less than that in Escherichia coli, another Gram-negative bacteria. Furthermore, ACF-HCl demonstrates synergistic effect with clarithromycin, a commonly used antibiotic against H. pylori. ACF-HCl treatment also eradicates H. pylori infection in the mice model efficiently. Our in vitro data indicate that bacterial membrane is the prime target. The novel action of ACF-HCl against antibiotic-resistant clinical isolates, synergistic effect with the conventional antibiotic clarithromycin and eradication of H. pylori from infected mice highlight the potential of ACF-HCl as a promising therapeutic agent against H. pylori by itself as well as for combinatorial therapy.

Background: Helicobacter pylori (H. pylori) is known to cause several gastro-duodenal diseases including chronic Gastritis, Peptic Ulcer disease and Gastric Cancer. Virulent genes of H. pylori like cagA, vacA are known to be responsible for the disease pathogenesis. But these virulence genes are not always found to be associated with disease outcome in all populations around the world. Relationship of H. pylori with Gastro Esophageal Reflux Diseases is controversial and uncertain. Tumor necrosis factor alpha inducing protein tipα is a new discovered virulent gene of H. pylori and is an inducer of certain cytokines and chemokines that are responsible for causing stomach cancer. Therefore, we conducted a study which aims to find the prevalence of tipα gene in the Indian population and its association with H. pylori related upper gastrointestinal diseases.Results: 267 clinical H. pylori isolates are included in our study for finding the prevalence of tipα gene and its association with cagA and vacA gene using PCR assay. The current study shows the prevalence rate of tipα gene in the Indian population to be 59.9%. Our study has found a significant association (p < 0.05) of tipα gene with Non Ulcer Dyspepsia (NUD) and also an association of cagA and vacA s1m1 with Gastritis and Duodenal Ulcer.Conclusion: Our study demonstrates for the first time the presence of tipα as virulent factor of H. pylori strain in Indian population isolated from patients suffering from upper gastrointestinal diseases. Further, tipα is significantly associated with NUD but not with other upper gastrointestinal diseases in India.

Objectives Because of the rise in antimicrobial resistance, an inexpensive, diet-based treatment against Helicobacter pylori infection would be of great interest. The present study was performed to assess the in vitro effects of ellagic acid against clinical H. pylori strains that were resistant to antibiotics used for therapy and also to observe the morphological structure following treatment with ellagic acid. The effectiveness of ellagic acid in eradicating H. pylori infection in a murine (C57BL/6) infection model, one of the standard inbred mouse lines often used for experimental infection, was also assessed. Methods A total of 55 strains were screened. The agar dilution method was used to determine the susceptibility of isolates to test compounds. Transmission electron microscopy was used to observe the morphology following treatment with ellagic acid. The antibacterial activity of ellagic acid in an H. pylori SS1-infected mouse model and its effect on gastric mucosal injury were determined by histology and PCR. Results Ellagic acid inhibited the growth of all 55 of the H. pylori strains tested. The MIC of ellagic acid ranged from 5 to 30 mg/L, showing its bactericidal properties in vitro. Ellagic acid also demonstrated anti-H. pylori efficacy in eradication of this organism in an in vivo model, as well as restitution and repair of H. pylori-induced gastric mucosal damage. Conclusions The present study paves the way for the preventive and therapeutic use of ellagic acid against H. pylori infection and, thus, ellagic acid can be considered a promising antibacterial agent against H. pylori-associated gastroduodenal diseases in humans.

Many bacterial genomes exclusively display an N4-methyl cytosine base (m4C), whose physiological significance is not yet clear. Helicobacter pylori is a carcinogenic bacterium and the leading cause of gastric cancer in humans. Helicobacter pylori strain 26695 harbors a single m4C cytosine methyltransferase, M2.HpyAII which recognizes 5′ TCTTC 3′ sequence and methylates the first cytosine residue. To understand the role of m4C modification, M2.hpyAII deletion strain was constructed. Deletion strain displayed lower adherence to host AGS cells and reduced potential to induce inflammation and apoptosis. M2.hpyAII gene deletion strain exhibited reduced capacity for natural transformation, which was rescued in the complemented strain carrying an active copy of M2.hpyAII gene in the genome. Genome-wide gene expression and proteomic analysis were carried out to discern the possible reasons behind the altered phenotype of the M2.hpyAII gene deletion strain. Upon the loss of m4C modification a total of 102 genes belonging to virulence, ribosome assembly and cellular components were differentially expressed. The present study adds a functional role for the presence of m4C modification in H. pylori and provides the first evidence that m4C signal acts as a global epigenetic regulator in H. pylori.

Background: Almost all Helicobacter pylori infected person develop gastritis and severe gastritis is supposed to be the denominator of peptic ulcer diseases, which may lead to gastric cancer. However, it is still an enigma why few strains are associated with ulcer formation, while others are not related with any disease outcome. Although a number of putative virulence factors have been reported for H. pylori, there are contradictory results regarding their connotation with diseases. Recently, there has been a significant attention in strain-specific genes outside the cag pathogenicity island, especially genes within plasticity regions. Studies demonstrated that certain genes in this region may play important roles in the pathogenesis of H. pylori-associated diseases. The aim of this study was to assess the role of selected genes (jhp0940, jhp0945, jhp0947 and jhp0949) in the plasticity region in relation to risk of H. pylorirelated diseases in Indian population. Methods: A total of 113 H. pylori strains isolated from duodenal ulcer (DU) (n = 61) and non-ulcer dyspepsia (NUD) subjects (n = 52) were screened by PCR and Dot-Blot to determine the presence of these genes. The comparative study of IL-8 production and apoptosis were also done by co-culturing the AGS cells with H. pylori strains of different genotype. Results: PCR and Dot-Blot results indicated that the prevalence rates of jhp0940, jhp0945, jhp0947 and jhp0949 in the H. pylori strains were 9.8, 47.5, 50.8, 40.9 % and 17.3, 28.8, 26.9, 19.2 % isolated from DU and NUD, respectively. IL-8 production and apoptotic cell death were significantly higher in H. pylori strains containing jhp0945, jhp0947 and jhp0949 than the strains lacking those genes. Results indicated that the prevalence of jhp0945, jhp0947 and jhp0949 are associated with increased risk of severe diseases in India. Conclusion: Our study showed that presence of jhp0945, jhp0947 and jhp0949 were significantly associated with symptomatic expressions along with the increased virulence during in vitro study whereas jhp0940 seems to be negatively associated with the disease. These results suggest that jhp0945, jhp0947 and jhp0949 could be useful prognostic markers for the development of duodenal ulcer in India.