High Prevalence ofHelicobacter pylori hopQII Genotype Isolated from Iranian Patients with Gastroduodenal Disorders

Helicobacter pyloriplays an important role in the pathogenesis of chronic gastritis, peptic ulceration, and noncardia gastric cancer. Several putative virulence factors forH. pylorihave been identified includingvacA,babA, andiceA. HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also play a role in the virulence ofH. pylori. Due to the substantial geographic differences in the prevalence ofH. pylorivirulence factors reported, the main purpose of the current study was to investigate the association between differentH. pylorivirulencehopQalleles (types I and II) and patients with gastroduodenal disorders. The presence ofH. pyloriandhopQalleles in gastric biopsy specimens was identified by specific PCR assays.H. pyloritype IIhopQwas found to be significantly associated with gastric cancer patients (odds ratio: 3.47, 95% CI: 1.56–5.89). Information about the prevalence ofH. pylori hopQtype II can be used for determining the high-risk diseases type which is actually colonized byH. pylori hopQtype II positive strains. The presence ofH. pylori hopQtype II should be investigated in different geographical regions as confirmatory findings may provide a definite biomarker attributed to the pathogenesis of certain severe digestive diseases.

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Pathogenesis ofHelicobacter pylori-Related Gastroduodenal Diseases from Molecular Epidemiological Studies

Gastroenterology Research and Practice ◽

10.1155/2012/371503 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 42

Author(s):

Yoshio Yamaoka

Keyword(s):

Gastric Cancer ◽

Virulence Factors ◽

Epidemiological Studies ◽

Sequencing Technology ◽

Disease Spectrum ◽

Genome Wide ◽

A Genome ◽

High Prevalence ◽

Different Types ◽

H Pylori

Helicobacter pyloriis a major human pathogen that infects the stomach and produces inflammation that is responsible for various gastroduodenal diseases. Despite the high prevalence ofH. pyloriinfections in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. The incidence of gastric cancer also tends to decrease from north to south in East Asia. Data from molecular epidemiological studies show that this variation in different geographic areas could be explained in part by different types ofH. pylorivirulence factors, especially CagA, VacA, and OipA.H. pyloriinfection is thought to be involved in both gastric cancer and duodenal ulcer, which are at opposite ends of the disease spectrum. This discrepancy can also be explained in part by anotherH. pylorifactor, DupA, as well as by CagA typing (East Asian type versus Western type).H. pylorihas a genome of approximately 1,600 genes; therefore, there might be other novel virulence factors. Because genome wide analyses using whole-genome sequencing technology give a broad view of the genome ofH. pylori, we hope that next-generation sequencers will enable us to efficiently investigate novel virulence factors.

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Lack of association between gastric cancer and hopQ alleles in Helicobacter pylori

Genetika ◽

10.2298/gensr1603893k ◽

2016 ◽

Vol 48 (3) ◽

pp. 893-902 ◽

Cited By ~ 1

Author(s):

Elham Kazemi ◽

Danial Kahrizi

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Acute Inflammation ◽

Outer Membrane Proteins ◽

Healthy Individuals ◽

Specific Primers ◽

Stomach Acid ◽

H Pylori ◽

Peripheral Cells ◽

Gastroduodenal Disorders

Helicobacter pylori use a number of mechanisms to survive in the stomach lumen. The presence of these bacteria in the stomach can lead to gastritis and reduction in stomach acid production. Acute inflammation can directly damage to the peripheral cells that are responsible for the secretion of acid. The risk of developing gastric carcinoma is associated to heterogeneity of Helicobacter pylori virulence factors (such as cagA). The HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also play a role in the virulence of H. pylori. This gene has been shown in two types. The purpose of the current study was to investigate the association between different H. pylori virulence hopQ alleles (types I and II) and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies the of patients with gastric cancer and 100 saliva samples from healthy individuals were collected. Then genomic DNA was purified and PCR for was done for desired genes via specific primers. The H. pylori infections were diagnosed by PCR for GlmM gene. Then frequencies of hopQI+, hopQII+ and hopQI+ hopQII+ genotypes were determined in H. pylori infected cases. Statistical analysis showed that there were not significant differences between healthy and diseased ones for genotypes hopQI+, hopQII+ and hopQI+ hopQII+.

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A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

Nature Communications ◽

10.1038/s41467-021-22317-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ryo Kinoshita-Daitoku ◽

Kotaro Kiga ◽

Masatoshi Miyakoshi ◽

Ryota Otsubo ◽

Yoshitoshi Ogura ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Patients ◽

Small Rna ◽

Outer Membrane Proteins ◽

Coding Region ◽

Host Environment ◽

Genes Encoding ◽

H Pylori ◽

Gastric Cancer Patients

AbstractLong-term infection of the stomach with Helicobacter pylori can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of H. pylori (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of H. pylori infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates H. pylori adaptation to the host environment and, potentially, gastric carcinogenesis.

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Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

Gut Pathogens ◽

10.1186/s13099-021-00419-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Zhijing Xue ◽

Yuanhai You ◽

Lihua He ◽

Yanan Gong ◽

Lu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Chinese Population ◽

Statistical Difference ◽

Variable Region ◽

Repeat Region ◽

Geographical Regions ◽

H Pylori ◽

Epiya Motifs

Abstract Background The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

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Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Cells ◽

10.3390/cells10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27

Author(s):

Jacek Baj ◽

Alicja Forma ◽

Monika Sitarz ◽

Piero Portincasa ◽

Gabriella Garruti ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Virulence Factors ◽

Premalignant Lesions ◽

Bacterial Pathogenicity ◽

Current State ◽

Genetic And Environmental Factors ◽

H Pylori ◽

Stimulation Of

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma

Pathogens ◽

10.3390/pathogens10030331 ◽

2021 ◽

Vol 10 (3) ◽

pp. 331

Author(s):

Montserrat Palau ◽

Núria Piqué ◽

M. José Ramírez-Lázaro ◽

Sergio Lario ◽

Xavier Calvet ◽

...

Keyword(s):

Helicobacter Pylori ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Virulence Factors ◽

Outer Membrane Proteins ◽

Whole Genome ◽

Flagellar Biosynthesis ◽

H Pylori ◽

Restriction Modification

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

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Diversity of 3’ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

10.21203/rs.3.rs-127429/v2 ◽

2021 ◽

Author(s):

Zhijing Xue ◽

Yuanhai You ◽

Lihua He ◽

Yanan Gong ◽

Lu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Chinese Population ◽

Statistical Difference ◽

Variable Region ◽

Repeat Region ◽

Geographical Regions ◽

H Pylori ◽

Epiya Motifs

Abstract Background: The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3’ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases.Methods: A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3’ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software.Results: A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B’, B’’ and D’) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which include AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographic regions (P = 0.006). There are seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acid residue 893 and 894 had a statistical difference with gastric cancer (P = 0.004).Conclusions: In this study, 503 CagA sequences was studied and analyzed in depth. In Chinese population, most H. pylori strains are of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.

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Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients

Cancers ◽

10.3390/cancers11050725 ◽

2019 ◽

Vol 11 (5) ◽

pp. 725 ◽

Cited By ~ 2

Author(s):

Tegshee Tserentogtokh ◽

Boldbaatar Gantuya ◽

Phawinee Subsomwong ◽

Khasag Oyuntsetseg ◽

Dashdorj Bolor ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Patients ◽

East Asian ◽

Virulent Strains ◽

Virulent Type ◽

High Incidence ◽

Caga Status ◽

H Pylori ◽

Gastric Cancer Patients

Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Tyr-Ala (EPIYA) segments) and vacA genotypes (s and m regions) were determined using PCR-based sequencing and PCR, respectively. In total, 368 patients were examined (341 gastritis, 10 peptic ulcer, and 17 gastric cancer). Sixty-two (16.8%) strains were cagA-negative and 306 (83.1%) were cagA-positive (293 Western-type, 12 East-Asian-type, and one hybrid type). All cagA-negative strains were isolated from gastritis patients. In the gastritis group, 78.6% (268/341) had Western-type CagA, 2.9% (10/341) had East-Asian-type, and 18.2% (61/341) were cagA-negative. However, all H. pylori from gastric cancer patients possessed Western-type CagA. Histological analyses showed that East-Asian-type CagA was the most virulent strains, followed by Western-type and cagA-negative strains. This finding agreed with the current consensus. CagA-positive strains were the most virulent type. However, the fact that different CagA types can explain the high incidence of gastric cancer might be inapplicable in Mongolia.

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