scholarly journals Whole Genome Sequencing Reveals Virulence Potentials of Helicobacter pylori Strain KE21 Isolated from a Kenyan Patient with Gastric Signet Ring Cell Carcinoma

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 556
Author(s):  
Catherine Mwangi ◽  
Stephen Njoroge ◽  
Evariste Tshibangu-Kabamba ◽  
Zahir Moloo ◽  
Allan Rajula ◽  
...  

Helicobacter pylori (H.pylori) infection is etiologically associated with severe diseases including gastric cancer; but its pathogenicity is deeply shaped by the exceptional genomic diversification and geographic variation of the species. The clinical relevance of strains colonizing Africa is still debated. This study aimed to explore genomic features and virulence potentials of H. pylori KE21, a typical African strain isolated from a native Kenyan patient diagnosed with a gastric cancer. A high-quality circular genome assembly of 1,648,327 bp (1590 genes) obtained as a hybrid of Illumina Miseq short reads and Oxford Nanopore MinION long reads, clustered within hpAfrica1 population. This genome revealed a virulome and a mobilome encoding more than hundred features potentiating a successful colonization, persistent infection, and enhanced disease pathogenesis. Furthermore, through an experimental infection of gastric epithelial cell lines, strain KE21 showed the ability to promote interleukin-8 production and to induce cellular alterations resulting from the injection of a functional CagA oncogene protein into the cells. This study shows that strain KE21 is potentially virulent and can trigger oncogenic pathways in gastric epithelial cells. Expended genomic and clinical explorations are required to evaluate the epidemiological importance of H. pylori infection and its putative complications in the study population.

2013 ◽  
pp. 118-125
Author(s):  
Quy Hung Le ◽  
Thi Minh Thi Ha

Background: H. pylori is the first cause of gastric cancer (GC). However, the role of cagA gene and vacA gene in GC is still controversial. This study is aimed at determining the rates of H. pylori infection, cagA gene, vacA genotypes in patients with GC; and evaluating the relationship between cagA gene, vacA genotypes and endoscopic and histopathological features of gastric cancer. Patients and methods: Fifty eight GC patients and one hundred and sixteen non-GC patients (controls) were enrolled. Infection of H. pylori was determined by PCR. cagA gene and vacA genotypes were determined by Multiplex PCR. Results: The rate of H. pylori was found in 55.2% in GC group. The rate of cagA gene and vacA gene in GC patients H. pylori positive were found in 78.1% and 100%, respectively. vac A genotypes s1/m1, s1/m2 and s1/m1m2 were found in 34.4%; 50% and 15.6%, respectively. The risk of GC of cagA positive group was higher than cagA negative group, with OR = 4,5; 95%CI = 1.6-12.2. The risk of GC of vacA s1/m1, cagA positive group was higher than vacA s1/m1, cagA negative group, OR = 7.1; 95%CI = 1.4-36. A statistically significative difference of rate of cagA positive was found between Borrmann III/IV group (100%) and Borrmann I/II group (46.2%). A statistically significative difference of rate of cagA positive was found between the tubular adenocarcinoma group (100%) and signet-ring cell carcinoma (44.4%, p = 0,002), and mucinous adenocarcinoma (50%, p =0,024). Conclusion: Gene cagA and vacA s1/m1 genotype were both risk factors in GC. A significative differences of rate of cagA positive were found between Borrmann groups, and between groups of WHO histopathological classification. Key words: cagA gene and vacA genotype, Helicobacter pylori, gastric cancer


2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Yoshitsugu Misumi ◽  
Shin Ichihara ◽  
Kouichi Nonaka ◽  
Hiromi Onizuka ◽  
Yoji Nagashima

The widespread use of Helicobacter pylori eradication therapy in recent years has reduced the H. pylori infection rate, indicating that gastric cancer cases diagnosed in the future may be H. pylori-naïve. The typical endoscopic presentation of signet-ring cell carcinoma, which accounts for the majority of H. pylori-naïve gastric cancer cases, is a discolored, flat, or depressed lesion; it is rarely presented as an elevated lesion. In this study, we treated a patient with elevated signet-ring cell carcinoma in an H. pylori-naïve stomach. Histopathological testing after endoscopic submucosal dissection showed proliferation of fibromuscular tissue in the tumor, which may have caused the formation of the elevated lesion.


Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.


2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.


2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.


Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.


Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 650
Author(s):  
Davide Giuseppe Ribaldone ◽  
Carlo Zurlo ◽  
Sharmila Fagoonee ◽  
Chiara Rosso ◽  
Angelo Armandi ◽  
...  

Updated data about the prevalence of Helicobacter pylori (H. pylori) and its correlation with histological results are scarce. The aim of our study was to provide current data on the impact of H. pylori in a third-level endoscopy service. We performed a large, retrospective study analyzing the results of all histological samples of gastroscopy from the year 2019. In total, 1512 subjects were included. The prevalence of H. pylori was 16.8%. A significant difference between the prevalence in subjects born in Italy and those from eastern Europe, south America, or Africa was found (p < 0.0001, p = 0.006, and p = 0.0006, respectively). An association was found between H. pylori and active superficial gastritis (p < 0.0001). Current H. pylori and/or a previous finding of H. pylori was related to antral atrophy (p < 0.0001). Fifteen patients had low-grade dysplasia. There were no statistically significant associations with current or past H. pylori infection. One patient presented gastric cardia adenocarcinoma with regular gastric mucosa. One patient, H. pylori positive, was diagnosed with gastric signet ring cell adenocarcinoma in a setting of diffuse atrophy, without metaplasia.. Our study provides updated, solid (biopsy diagnosis and large population) data on the prevalence of H. pylori infection in a representative region of southern Europe.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  

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.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Jacek Baj ◽  
Alicja Forma ◽  
Monika Sitarz ◽  
Piero Portincasa ◽  
Gabriella Garruti ◽  
...  

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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