• Helicobacter pylori
• gastric cancer
• gastric disease
• outer membrane protein
• virulence factor

• Helicobacter pylori/pathogenicity
• Helicobacter pylori/genetics
• Humans
• Virulence Factors/metabolism
• Helicobacter Infections/microbiology
• Bacterial Outer Membrane Proteins/metabolism
• Bacterial Vaccines/immunology
• Adhesins, Bacterial/metabolism
• Bacterial Proteins/metabolism
• Animals
• Antigens, Bacterial/metabolism

• Helicobacter pylori
• Adhesins
• Gastric ulcer
• OMVs
• Pathogenesis
• Virulence factors

• Humans
• Virulence/genetics
• Helicobacter pylori/genetics
• Peptic Ulcer/microbiology
• Stomach Neoplasms
• Virulence Factors/genetics
• Bacterial Proteins/genetics
• Antigens, Bacterial/genetics

• EPIYA-C motif
• Helicobacter pylori
• cagA
• geographic diversity
• polymorphism

• Gastric cancer
• Helicobacter pylori
• HomB gene
• MALT
• Peptic ulcer

• Antigens, Bacterial
• Bacterial Proteins
• Helicobacter Infections/epidemiology
• Helicobacter pylori/genetics
• Humans
• Peptic Ulcer/epidemiology
• Stomach Neoplasms/epidemiology
• Virulence Factors

Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori–related diseases.

• Helicobacter pylori
• Outer membrane proteins
• Virulence factors

Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.

• Helicobacter pylori
• Virulence genes
• Disease association
• Children
• Adults
• Outer membrane proteins
• Bacterial toxins

• Adhesins, Bacterial/genetics
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Genes, Bacterial
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Humans
• Prevalence
• Virulence/genetics
• Virulence Factors/genetics

• Children
• Gastritis
• Helicobacter pylori
• Virulence genes
• homA gene
• homB gene

• Child
• Gene Frequency
• Genes, Bacterial
• Genotype
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Histocytochemistry
• Humans
• Severity of Illness Index
• Slovenia
• Virulence Factors/genetics

One elusive area in the Helicobacter pylori field is an understanding of why some infections result in gastric cancer, yet others persist asymptomatically for the life-span of the individual. Even before the genomic era, the high level of intraspecies diversity of H. pylori was well recognized and became an intriguing area of investigation with respect to disease progression. Of interest in this regard is the unique repertoire of over 60 outer membrane proteins (OMPs), several of which have been associated with disease outcome. Of these OMPs, the association between HomB and disease outcome varies based on the population being studied. While the molecular roles for some of the disease-associated OMPs have been evaluated, little is known about the role that HomB plays in the H. pylori lifecycle. Thus, herein we investigated homB expression, regulation, and contribution to biofilm formation. We found that in H. pylori strain G27, homB was expressed at a relatively low level until stationary phase. Furthermore, homB expression was suppressed at low pH in an ArsRS-dependent manner; mutation of arsRS resulted in increased homB transcript at all tested time-points. ArsRS regulation of homB appeared to be direct as purified ArsR was able to specifically bind to the homB promoter. This regulation, combined with our previous finding that ArsRS mutations lead to enhanced biofilm formation, led us to test the hypothesis that homB contributes to biofilm formation by H. pylori. Indeed, subsequent biofilm analysis using a crystal-violet quantification assay and scanning electron microscopy (SEM) revealed that loss of homB from hyper-biofilm forming strains resulted in reversion to a biofilm phenotype that mimicked wild-type. Furthermore, expression of homB in trans from a promoter that negated ArsRS regulation led to enhanced biofilm formation even in strains in which the chromosomal copy of homB had been deleted. Thus, homB is necessary for hyper-biofilm formation of ArsRS mutant strains and aberrant regulation of this gene is sufficient to induce a hyper-biofilm phenotype. In summary, these data suggest that the ArsRS-dependent regulation of OMPs such as HomB may be one mechanism by which ArsRS dictates biofilm development in a pH responsive manner.

• ArsRS
• H. pylori
• OMPs
• biofilms
• homB

To be able to survive, Helicobacter pylori must adhere to the gastric epithelial cells of its human host. For this purpose, the bacterium employs an array of adhesins, for example, AlpA. The adhesin AlpA has been proposed as a major adhesin because of its critical role in human stomach colonization. Therefore, understanding how AlpA evolved could be important for the development of new diagnostic strategies. However, the genetic variation and microevolutionary patterns of alpA have not been described in Colombia. The study aim was to describe the variation patterns and microevolutionary process of alpA in Colombian clinical isolates of H. pylori. The existing polymorphisms, which are deviations from the neutral model of molecular evolution, and the genetic differentiation of the alpA gene from Colombian clinical isolates of H. pylori were determined. The analysis shows that gene conversion and purifying selection have shaped the evolution of three different variants of alpA in Colombia.

• AlpA adhesin.
• Gene convergence
• Helicobacter pylori
• Purifying selection
• Rapid evolution

• Helicobacter pylori
• Hom
• outer membrane proteins

• Gastrointestinal disease
• Helicobacter pylori
• Pathogenic gene
• Polymorphism

• Gastrointestinal Diseases/diagnosis
• Gastrointestinal Diseases/microbiology
• Genotype
• Helicobacter Infections/diagnosis
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions
• Humans
• Phenotype
• Polymorphism, Genetic
• Virulence
• Virulence Factors/genetics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Bacterial/genetics
• Bacterial Outer Membrane Proteins/genetics
• Bacterial Proteins/genetics
• Female
• Genetic Variation
• Genotype
• Genotyping Techniques
• Helicobacter pylori/classification
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Hospitals
• Humans
• Male
• Middle Aged
• Phylogeny
• Republic of Korea
• Sequence Homology, Nucleic Acid
• United States

• P30 DK058404 NIDDK NIH HHS
• R01 CA077955 NCI NIH HHS

• Epidemiology
• Genome
• Helicobacter pylori
• Mutation
• Recombination

• Asia
• Genetic Variation
• Genome Size
• Genome, Bacterial
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Humans
• Mutation
• Phylogeny
• Prevalence
• Recombination, Genetic
• Stomach/microbiology

AIM: To evaluate the contribution of the G-197A polymorphism in the interleukin-17 (IL-17) promoter region to gastric cancer risk in an Iranian population.

METHODS: We performed a case control study using samples from 161 individuals with gastric cancer and 171 healthy controls. For each individual, the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments. Statistical analyses were performed to determine whether any demographic or behavioral factors, infection with Helicobacter pylori (H. pylori), or a particular G-197A genotype was associated with gastric cancer risk.

RESULTS: We found that the G-197A genotype was significantly associated with increased gastric cancer risk (P = 0.001). Patients who were homozygous (AA) at position -197 were 2.9 times more likely to develop disease (95%CI: 1.56-5.4; P = 0.001). Furthermore, logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold (95%CI: 1.26-2.369; P = 0.001). This association was observed for early stage gastric adenocarcinomas only, and was not linked to H. pylori infection.

CONCLUSION: These results suggest that carrying one or more G-197A polymorphisms at position -197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

• Gastric cancer
• Interleukin-17A
• Cancer
• Helicobacter pylori

• Adenocarcinoma/epidemiology
• Adenocarcinoma/genetics
• Adult
• Aged
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-17/genetics
• Iran/epidemiology
• Male
• Middle Aged
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/genetics

Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1) colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2) evasion from the human immune system and (3) efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence.

• Gastric cancer
• Helicobacter pylori
• Heterozygous CT genotype
• Homozygous TT genotype
• Inducible nitric oxide synthetase

• Adult
• Aged
• Aged, 80 and over
• Beverages/adverse effects
• Case-Control Studies
• Chi-Square Distribution
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Heterozygote
• Homozygote
• Hot Temperature
• Humans
• Iran/epidemiology
• Logistic Models
• Male
• Middle Aged
• Nitric Oxide Synthase Type II/genetics
• Odds Ratio
• Phenotype
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Risk Assessment
• Risk Factors
• Smoking/adverse effects
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology

In the past decade, researchers have proposed that the pldA gene for outer membrane phospholipase A (OMPLA) is important for bacterial colonization of the human gastric ventricle. Several conserved Helicobacter pylori genes have distinct genotypes in different parts of the world, biogeographic patterns that can be analyzed through phylogenetic trees. The current study will shed light on the importance of the pldA gene in H. pylori. In silico sequence analysis will be used to investigate whether the bacteria are in the process of preserving, optimizing, or rejecting the pldA gene. The pldA gene will be phylogenetically compared to other housekeeping (HK) genes, and a possible origin via horizontal gene transfer (HGT) will be evaluated through both intra- and inter-species evolutionary analyses.

In this study, pldA gene sequences were phylogenetically analyzed and compared with a large reference set of concatenated HK gene sequences. A total of 246 pldA nucleotide sequences were used; 207 were from Norwegian isolates, 20 were from Korean isolates, and 19 were from the NCBI database. Best-fit evolutionary models were determined with MEGA5 ModelTest for the pldA (K80 + I + G) and HK (GTR + I + G) sequences, and maximum likelihood trees were constructed. Both HK and pldA genes showed biogeographic clustering. Horizontal gene transfer was inferred based on significantly different GC contents, the codon adaptation index, and a phylogenetic conflict between a tree of OMPLA protein sequences representing 171 species and a tree of the AtpA HK protein for 169 species. Although a vast majority of the residues in OMPLA were predicted to be under purifying selection, sites undergoing positive selection were also found.

Our findings indicate that the pldA gene could have been more recently acquired than seven of the HK genes found in H. pylori. However, the common biogeographic patterns of both the HK and pldA sequences indicated that the transfer occurred long ago. Our results indicate that the bacterium is preserving the function of OMPLA, although some sites are still being evolutionarily optimized.

The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.

Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries.

Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.

• Americas
• Amino Acid Sequence
• Asia
• Bacterial Proteins/genetics
• DNA, Bacterial/chemistry
• DNA, Bacterial/genetics
• Emigration and Immigration
• Europe
• Genetic Variation
• Genome, Bacterial/genetics
• Helicobacter Infections/microbiology
• Helicobacter pylori/classification
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Humans
• Indians, South American
• Molecular Sequence Data
• Peru
• Phylogeny
• Population Dynamics
• Sequence Analysis, DNA
• Sequence Homology, Amino Acid
• Species Specificity
• Time Factors

• R21 AI078237 NIAID NIH HHS
• R21 AI088337 NIAID NIH HHS
• 5R24 TW007988 FIC NIH HHS
• R01 DK63041 NIDDK NIH HHS
• R01 DK063041 NIDDK NIH HHS
• R24 TW007988 FIC NIH HHS

The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail.

Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing.

Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh.

H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.