Genotyping Helicobacter pylori and fgf7 gene expression in gastric cancer.

BACKGROUND: Helicobacter pylori as the causative agent of the most common chronic bacterial infectious disease in human still involves a range of clinical challenging complications. In this meantime, the survey of the interaction between H. pylori virulence genes expression and its consequences on gastric antral epithelial cells is Controversial. This study surveyed the correlations between H. pylori cag Pathogenicity Island and virulence factors genes with Fgf7 gene expression as an angiogenic factor in developing gastric cancer in gastric antral epithelial cells of patients with H. pylori infection. METHOD: Gastric antral biopsy samples collected from patients out of exclusion criteria, including consumption of tobacco, alchohol and anti-H. pylori drugs, were categorized into gastric cancer (case group n:53) and gastritis (control group n:50) with and without H. pylori infection to detect changes in cDNA of fgf7 in gastric antral epithelial cells by using Real Time RT PCR. Extracted total RNA from gastric antral biopsy samples was used to synthesize cDNA for real time PCR. Furthermore, the cDNA of H. pylori cag Pathogenicity Island and other virulence factors genes were detected by using specific designed primers and simple PCR. RESULTS: Fgf7 gene expression revealed a significantly increase in gastric antral epithelial cells of gastric cancer and H. pylori-positive patients in contrast with gastritis and H. pylori-negative patients (p < 0.05). In the meanwhile, cag Pathogenicity Island and hopQ genotypes showed a positive correlation with Fgf7 gene expression (fold changes of cDNA) in gastric antral epithelial cells (p < 0.05). CONCLUSION: This study revealed an obvious correlation between Fgf7 gene expression in gastric antral epithelial cells of patients with H. pylori carcinogenic genotypes infection and some host factors including age.

Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population.

Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.

Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity.

Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world's population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.

Changes of tight junction and interleukin-8 expression using a human gastroid monolayer model of Helicobacter pylori infection.

BACKGROUND: Lack of a model that mirrors Helicobacter pylori-induced gastric mucosal inflammation has hampered investigation of early host-bacterial interactions. We used an ex vivo model of human stomach, gastric epithelial organoid monolayers (gastroid monolayers) to investigate interactions of H pylori infection and the apical junctional complex and interleukin-8 (IL-8) expression. METHOD: Morphology of human antral mucosal gastroid monolayers was evaluated using histology, immunohistochemical (IHC) staining, and transmission electron microscopy (TEM). Functional and gross changes in the apical junctional complexes were assessed using transepithelial electrical resistance (TEER), cytotoxicity assays, and confocal laser scanning microscopy. IL-8 expression was evaluated by real-time quantitative PCR and ELISA. RESULTS: When evaluated by IHC and TEM, the morphology of gastroid monolayers closely resembled in vivo human stomach. Following inoculation of H pylori, TEER transiently declined (up to 51%) in an H pylori density-dependent manner. TEER recovered by 48 hours post-infection and remained normal despite continued presence and replication of H pylori. Confocal scanning microscopy showed minimal disruption of zonula occludens-1 or E-cadherin structure. IL-8 production was unchanged by infection with either CagA-positive or CagA-negative H pylori and JNK and MEK inhibitors did not suppress IL-8 production, whereas p38 and IKK inhibitor significantly did. CONCLUSION: Human gastroid monolayers provide a model for experimental H pylori infection more consistent with in vivo human infections than seen with typical gastric epithelial cell lines. This ex vivo system should lead to better understanding of H pylori host-pathogen interactions.

Application of proteomics to the study of Helicobacter pylori and implications for the clinic.

INTRODUCTION: Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric epithelium and mucous layer of more than half the world's population. H. pylori is a primary human pathogen, responsible for the development of chronic gastritis, peptic ulceration and gastric cancer. Proteomics is impacting several aspects of medical research: understanding the molecular basis of infection and disease manifestation, identification of therapeutic targets and discovery of clinically relevant biomarkers. Areas covered: The main aim of the present review is to provide a comprehensive overview of the contribution of proteomics to the study of H. pylori infection pathophysiology. In particular, we focused on the role of the bacterium and its most important virulence factor, CagA, in the progression of gastric cells transformation and cancer progression. We also discussed the proteomic approaches aimed at the investigation of the host response to bacterial infection. Expert commentary: In the field of proteomics of H. pylori, comprehensive analysis of clinically relevant proteins (functional proteomics) rather than entire proteomes will result in important medical outcomes. Finally, we provided an outlook on the potential development of proteomics in H. pylori research.

In vitro culture and phenotypic and molecular characterization of gastric stem cells from human stomach.

BACKGROUND: Human gastric mucosa shows continuous self-renewal via differentiation from stem cells that remain poorly characterized. METHODS: We describe an original protocol for culture of gastric stem/progenitor cells from adult human stomach. The molecular characteristics of cells were studied using TaqMan low-density array and qRT-PCR analyses using the well-characterized H1 and H9 embryonic stem cells as reference. Epithelial progenitor cells were challenged with H. pylori to characterize their inflammatory response. RESULTS: Resident gastric stem cells expressed specific molecular markers of embryonic stem cells (SOX2, NANOG, and OCT4), as well as others specific to adult stem cells, particularly LGR5 and CD44. We show that gastric stem cells spontaneously differentiate into epithelial progenitor cells that can be challenged with H. pylori. The epithelial progenitor response to H. pylori showed a cag pathogenicity island-dependent induction of matrix metalloproteinases 1 and 3, chemokine (CXCL1, CXCL5, CXCL8, CCL20) and interleukine 33 expression. CONCLUSION: This study opens new outlooks for investigation of gastric stem cell biology and pathobiology as well as host-H. pylori interactions.

Pathogenesis of Helicobacter pylori Infection.

Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence, and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA, and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infection. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cagPAI, CagA, VacA, and gastrointestinal microbiota.

Pathogenesis of Helicobacter pylori infection.

Helicobacter pylori infection and disease outcome are mediated by a complex interplay between bacterial, host, and environmental factors. Over the past year, our understanding of this complex interplay has been improved by a variety of studies focusing on both host and bacterial factors. These include studies assessing novel virulence factors as well as those most frequently associated with severity of disease outcome including cagA and the cag pathogenicity island, and the vacuolating cytotoxin. Several studies have focused on regulation of virulence factors by environmental factors. In addition, mechanisms by which bacterial virulence factors influence the host response and disease, by inducing epigenetic changes, autophagy and altered oxidative stress have also been elucidated. This review highlights key findings in the pathogenesis of H. pylori infection reported over the past year.

The signal conversion strategy using the lytic transglycosylase Cag4-double nanoporous gold co-catalysis for the rapid screening of drugs against Helicobacter pylori infection.

The cag pathogenicity island (cagPAI) is the main virulence factor of gastric carcinoma induced by Helicobacter pylori (H. pylori). The lytic transglycosylase Cag4 is an important component that assists in the translocation of the bacterial oncoprotein CagA and maintains the peptidoglycan cycle. The allosteric regulation of Cag4 has been preliminarily demonstrated to inhibit H. pylori infection. Unfortunately, a rapid screening technology for allosteric regulators of Cag4 has not been established. In this study, a novel Cag4-double nanoporous gold (NPG) biosensor based on enzyme-inorganic co-catalysis was constructed using the heterologously expressed H. pylori 26695 Cag4 as the biological recognition element for screening Cag4 allosteric regulators. The results showed that chitosan or carboxymethyl chitosan was a mixed Cag4 inhibitor combining non-competition with uncompetition. The inhibition constants were Ki' Chitosan = 0.88909 mg/mL and Ki' Carboxymethyl chitosan = 1.13480 mg/mL, respectively. Surprisingly, D-(+)-cellobiose showed the activation effect of Cag4 on E. coli MG1655 cell wall lysis by decreasing the Ka value by 29.7% and increasing the Vmax value by 71.3%. In addition, molecular docking revealed the importance of the polarity of the C2 substituent group with glucose as the main structure in the Cag4 allosteric regulator. This study provides a fast and useful platform for screening potential new drugs based on the Cag4 allosteric regulator.

Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study.

BACKGROUND: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, most Helicobacter pylori strains in Mongolia have a less virulent Western-type CagA. We aimed to determine how H. pylori genomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. METHODS: We identified a set of 274 virulence-associated genes in H. pylori, including virulence factor and outer membrane protein (OMP) genes, the type four secretion system gene cluster, and 13 well-known virulence gene genotypes in 223 H. pylori strains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158 H. pylori strains (15 gastric cancer and 143 non-gastric cancer strains). RESULTS: Out of 274 genes, we found 13 genes were variable depending on disease outcome, especially iron regulating OMP genes. H. pylori strains from Mongolia were divided into two main subgroups: subgroup (Sg1) with high risk and Sg2 with low risk for gastric cancer. The general characteristics of Sg1 strains are that they possess more virulence genotype genes. We found nine non-synonymous single nucleotide polymorphisms in seven genes that are linked with gastric cancer strains. CONCLUSIONS: Highly virulent H. pylori strains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.

Helicobacter pylori and Its Role in Gastric Cancer.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and mitigating the burden of this life-threatening disease. This review aims to provide an overview of our current understanding of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

Profile of Helicobacter pylori cagA &vacA genotypes and its association with the spectrum of gastroduodenal disease.

PURPOSE: Globally, H. pylori virulence factors cagA and vacA genotypes and its variation is leading to the austere form of the gastroduodenal disease. Our objectives were to detect H. pylori in dyspeptic patients from biopsy samples with the validation of the various existing diagnostic tools and to screen the cagA, vacA genotypes profile from biopsy specimens and how it impacts in progression of gastroduodenal disease in southern India. METHODS: 374 patients who attended endoscopy unit at Kasturba Hospital, Manipal with their consent obtained their biopsies. H. pylori were detected by HPE, Culture, RUT and PCR and its virulence gene were patterned with PCR. RESULTS: The positive rate of H. pylori by HPE, RUT, Culture and PCR were 51.33%, 47.1%, 32.4% and 50.3% respectively and comparison by Bayesian LCMs analysis showed PCR is superior among them. The frequency of H. pylori virulence gene viz cagPAI (cagA) were 80.9%, and vacA alleles-s1m1 (42%), s1m2 (33%) and s2m2 (25%) genotypes by PCR respectively. Four combinations of cagA/vacA genotypes were noted, majority of strains harboured cagA+/vacA s1m1 genotypes (42.6%), interestingly this hyper-virulent strain more frequently seen in severe gastroduodenal disease whereas cagPAI negative strains as well as cagA-/vacA s2m2 combinations (19.1%) are seen most commonly in functional dyspepsia cases and depicted significant association by Chi-square test. CONCLUSIONS: This study validates and compares the existing diagnostic methods for detecting H. pylori in biopsies. Also, it reveals some pattern of virulence gene combination will play a vital role in disease progression.

Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand.

There is a lack of evidence of genetic variation in the Helicobacter pylori cag-PAI in Thailand, a region with the low incidence of gastric cancer. To clarify this issue, variation in the H. pylori cag-PAI in strains detected in Thailand was characterized and simultaneously compared with strains isolated from a high-risk population in Korea. The presence of ten gene clusters within cag-PAI (cagA, cagE, cagG, cagH, cagL, cagM, cagT, orf13, virB11, and orf10) and IS605 was characterized in H. pylori strains detected from these two countries. The cagA genotypes and EPIYA motifs were analyzed by DNA sequencing. The overall proportion of the ten cag-PAI genes that were detected ranged between 66 and 79%; additionally, approximately 48% of the strains from Thai patients contained an intact cag-PAI structure, while a significantly higher proportion (80%) of the strains from Korean patients had an intact cag-PAI. A significantly higher proportion of IS605 was detected in strains from Thai patients (55%). Analysis of cagA genotypes and EPIYA motifs revealed a higher frequency of Western-type cagA in Thai patients (87%) relative to Korean patients (8%) who were predominately associated with the East Asian-type cagA (92%). Variations in the Western-type cagA in the Thai population, such as EPIYA-BC patterns and EPIYA-like sequences (EPIYT), were mainly detected as compared with the Korean population (p < 0.05). In summary, H. pylori strains that colonize the Thai population tend to be associated with low virulence due to distinctive cag-PAI variation, which may partially explain the Asian paradox phenomenon in Thailand.

Crystal structure of CagV, the Helicobacter pylori homologue of the T4SS protein VirB8.

The VirB/D type IV secretion system (T4SS) plays an essential role in materials transport between host cells and pathogenic Helicobacter pylori and is considered the major pathogenic mediator of H. pylori-associated gastric disease. VirB8, an inner membrane protein that interacts with many other proteins, is a crucial component for secretory function. Here, we present a crystal structure of the periplasmic domain of CagV, the VirB8 counterpart in the H. pylori Cag-T4SS. The structure reveals a fold similar to that of other VirB8 members except for the absence of the α5 helix, a discontinuous ß1 strand, a larger angle between the α2 and α3 helices, a more hydrophobic surface groove, but exhibits a different dimer interface. Whether the dimerization occurs in solution was proved by mutagenesis, size-exclusion chromatography and cross-linking assays. Unlike the classical dimerization mode, the interface of the CagV dimer is principally formed by several hydrogen bonds, which indicates instability of dimerization. The structure here demonstrates the difference in dimerization among VirB8 homologues and indicates the considerable compositional and functional diversity of them in T4SS. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 6IQT.

The type IV secretion system in Helicobacter pylori.

Helicobacter pylori (H. pylori) has an essential role in the pathogenesis of gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. The severity of the host inflammatory responses against the bacteria have been straightly associated with a special bacterial virulence factor, the cag pathogenicity island, which is a type IV secretion system (T4SS) to deliver CagA into the host cells. Besides cag-T4SS, the chromosomes of H. pylori can encode another three T4SSs, including comB, tfs3 and tfs4. In this review, we systematically reviewed the four T4SSs of H. pylori and explored their roles in the pathogenesis of gastroduodenal diseases. The information summarized in this review might provide valuable insights into the pathogenic mechanism for H. pylori.

Phylogeographic diversity and mosaicism of the Helicobacter pylori tfs integrative and conjugative elements.

BACKGROUND: The genome of the gastric pathogen Helicobacter pylori is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the cag pathogenicity island (cagPAI) and two mobile integrative and conjugative elements (ICEs) termed tfs3 and tfs4. All three islands are implicated as virulence factors, although whereas the cagPAI is well characterised, understanding of how the tfs elements influence H. pylori interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global H. pylori population. RESULTS: To gain a global perspective of tfs ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full tfs pan-gene content contained within a global collection of 221 draft and complete H. pylori genome sequences. Complete (ca. 35-55kbp) and remnant tfs ICE clusters were reconstructed from a dataset comprising > 12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different tfs ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of tfs ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular H. pylori phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement. CONCLUSIONS: Our collective results establish a clear view of tfs ICE diversity and phylogeographic representation in the global H. pylori population, and provide a robust contextual framework for elucidating the functional role of the tfs ICEs particularly as it relates to the risk of gastric disease associated with different tfs ICE genotypes.

Helicobacter pylori Strains and Gastric MALT Lymphoma.

This article summarizes the main findings concerning Helicobacter pylori associated with gastric MALT lymphoma (GML). Considered together, GML strains based on their virulence factor profile appear to be less virulent than those associated with peptic ulcers or gastric adenocarcinoma. A particular Lewis antigen profile has been identified in GML strains and could represent an alternative adaptive mechanism to escape the host immune response thereby allowing continuous antigenic stimulation of infiltrating lymphocytes.

Attenuation of Helicobacter pylori-induced gastric inflammation by prior cag- strain (AM1) infection in C57BL/6 mice.

BACKGROUND: Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag+ strain (SS1) and cag- strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa. RESULTS: Mice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1ß and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3+ T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-ß were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues. CONCLUSIONS: These data suggested that prior H. pylori cag- strain infection attenuated the severity of gastric pathology induced by subsequent cag+ strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent H. pylori strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.

Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells.

Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128Δ cagM, a cag type IV secretion system defective strain. Signaling pathway involvement was investigated using inhibitors of epidermal growth factor receptor (EGFR), MAPK, JAK and blocking Abs against TLR2 and TLR4. Inhibitors of EGFR, MAPK and JAK significantly reduced the chemokine mRNA expression and production induced by both H. pylori strains at 3 h and 24 h post-infection. JNK inhibitor reduced chemokine production at 24 h post-infection. Blocking Abs against TLR2 but not TLR4 showed significant reduction of chemokine secretion. Using primary culture of human gastric epithelial cells, our data suggest that H. pylori can be recognized by TLR2, leading to chemokine induction, and that EGFR, MAPK and the JAK/STAT signaling pathways play a key role in the H. pylori-induced CXCL1, CXCL5 and CXCL8 response in a cag pathogenicity island-independent manner.

Characterization of the Cag pathogenicity island in Helicobacter pylori from naturally infected rhesus macaques.

Helicobacter pylori commonly infects the epithelial layer of the human stomach and in some individuals causes peptic ulcers, gastric adenocarcinoma or gastric lymphoma. Helicobacter pylori is a genetically diverse species, and the most important bacterial virulence factor that increases the risk of developing disease, versus asymptomatic colonization, is the cytotoxin associated gene pathogenicity island (cagPAI). Socially housed rhesus macaques are often naturally infected with H. pylori similar to that which colonizes humans, but little is known about the cagPAI. Here we show that H. pylori strains isolated from naturally infected rhesus macaques have a cagPAI very similar to that found in human clinical isolates, and like human isolates, it encodes a functional type IV secretion system. These results provide further support for the relevance of rhesus macaques as a valid experimental model for H. pylori infection in humans.