Variations in the multimerization region of the Helicobacter pylori cytotoxin CagA affect virulence

Ahire, Daiva; Alston, Tricia; Raffaniello, Robert D.

doi:10.3892/ol.2017.5562

Cited by 3 publications

(2 citation statements)

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“…This finding contradicts results from a previous study showing that cagA gene is associated with HBA [ 8 ]. This discrepancy might be explained by gene expression variation of cagA gene due to the genetic heterogeneity of promoter region [ 26 ], gene motifs [ 27 ], and copy number [ 28 ]. These genetic variations might cause the differential gene expression of cagA , which in turn affects the immune response.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

et al. 2021

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Despite the synergistic effect of Opisthorchis viverrini and Helicobacter pylori co-infection on pathogenesis of severe hepatobiliary abnormalities (HBA) including advanced periductal fibrosis and replace with cholangiocarcinoma (CCA) have been established, the immune response to H. pylori in O. viverrini infected population has never been explored. Hence, this study aimed to investigate the antibody responses to 2 immunogenic H. pylori proteins in O. viverrini-infected patients with HBA and CCA. The risk analysis by multinomial logistic regression revealed that GroEL seropositivity was associated with higher risks of hepatobiliary abnormalities and CCA with adjusted odds ratios (95% confidence intervals) of 2.11 (95% CI=1.20-3.71, P=0.008) and 2.13 (95% CI=1.21-3.75, P=0.009), respectively. These findings indicate that GroEL seropositivity might be a biomarker for early detection of O. viverrini associated HBA and CCA.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

et al. 2021

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“…Ahire et al [ 32 ] created both E-CM motif-transfected and W-CM motif-transfected strains and then compared the toxicities of these strains by testing with gastric epithelial cells. The E-CM motif used in that cloning study had the same sequence as the typical Af1-CM motif proposed by our group.…”

Section: Discussionmentioning

confidence: 99%

Discovery of unique African Helicobacter pylori CagA-multimerization motif in the Dominican Republic

Ono

Cruz

Nagashima

et al. 2020

WJG

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BACKGROUND Helicobacter pylori ( H. pylori ) colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer. However, although the prevalence of H. pylori is high in Africa, the incidence of gastric cancer is low, and this phenomenon is called to be African enigma. The CagA protein produced by H. pylori is the most studied virulence factor. The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns and CagA-multimerization (CM) motifs. AIM To better understand the EPIYA patterns and CM motifs of the cagA gene. METHODS Gastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic, from which 120 H. pylori strains were cultured. After the bacterial DNA extraction, the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing (MLST). Peptic ulcer disease and gastric cancer were identified via endoscopy, and gastric cancer was confirmed by histopathology. Histological scores of the gastric mucosa were evaluated using the updated Sydney system. RESULTS All CagA -positive strains carried the Western-type CagA according to the identified EPIYA patterns. Twenty-seven kinds of CM motifs were observed. Although the typical Western CM motif (FPLKRHDKVDDLSKVG) was observed most frequently, the typical East Asian CM motif (FPLRRSAAVNDLSKVG) was not observed. However, “FPLRRSAKVEDLSKVG”, similar to the typical East Asian CM motif, was found in 21 strains. Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis ( P = 0.034), we termed it Africa1-CM (Af1-CM). A few hpEurope strains carried the Af1-CM motif, but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif ( P = 0.030). In 30 cagA -positive strains, the "GKDKGPE" motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment, and there was a significant association between strains with the hpAfrica1 population and those containing the “GKDKGPE” motif ( P = 0.018). In contrast, there was no significant association between the CM motif patterns and histological scores and clinical outcomes. CONCLUSION We found the unique African CM motif in Western-type CagA and termed it Africa1-CM. The less toxicity of this motif could be one reason to explain the African enigma.

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Helicobacter pylori‐related risk predictors of gastric cancer: The latest models, challenges, and future prospects

2020

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Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co‐evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori‐related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry‐specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high‐risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age‐sex‐matched controls from high‐risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry‐specific. In addition, potential study‐level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.

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Variations in the multimerization region of the Helicobacter pylori cytotoxin CagA affect virulence

Abstract: Abstract. Helicobacter pylori colonizes the human stomach by infecting gastric epithelial cells.

Cited by 3 publications

References 30 publications

Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

Discovery of unique African Helicobacter pylori CagA-multimerization motif in the Dominican Republic

Helicobacter pylori‐related risk predictors of gastric cancer: The latest models, challenges, and future prospects

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