scholarly journals Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran

2013 ◽  
Vol 1 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Abolghasem Ajami ◽  
Mojtaba Shadman ◽  
Alireza Rafiei ◽  
Vahid Hosseini ◽  
Amin TalebiBezmin Abadi ◽  
...  
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.


PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96488 ◽  
Author(s):  
Judith Lind ◽  
Steffen Backert ◽  
Klaus Pfleiderer ◽  
Douglas E. Berg ◽  
Yoshio Yamaoka ◽  
...  

2021 ◽  
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 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.


2019 ◽  
Vol 18 (3) ◽  
pp. 577-585
Author(s):  
Ileana González ◽  
Lidice González ◽  
Armando Rojas ◽  
Boris L Rodríguez ◽  
Jacqueline Romero ◽  
...  

Background: The prevalence of Helicobacter pylori-related diseases varies geographically and it is partially determined by the virulence of the circulating strains. Cuba and Chile exhibit different gastric cancer rates, on despite of very similar H. pylori infection rates. We determined if differences in the pathogenic potential of H. pylori isolates from Chile and Cuba could explain the disease outcome in each population. Methods: H. pylori isolates from 78 Chilean and 71 Cuban patients were analyzed using PCR for the presence of cagA, babA2, vacA alleles and the pattern of EPIYA motifs. Results: cagA was detected in 94.9 % of Chilean and 64.7 % of Cuban isolates (P < 0.001) and was significantly associated with duodenal ulcer (DU) in Cuba (P < 0.01) but not in Chile. The presence of cagA with multiple EPIYA-C motifs was 18.2 % higher in Chile than in Cuba (P < 0.05). Also, an association was observed between GU (P ≤ 0.05) and premalignant lesions (P < 0.001) with the multiple EPIYA-C motif status of the strains in Chile, but not in Cuba. The prevalence of vacA s2m2 genotype was predominant in Chile (66.7 %), while in Cuba was prevalent the s1m1 genotype (56.8 %); and the last one was significantly associated with the presence of DU in Cuban patients. Conclusions: The cagA status and the EPIYA pattern found in Chilean and Cuban H. pylori clinical isolates partially explain the differences in disease prevalence between both countries. The high proportion of vacA s2m2 genotype in Chile was an unexpected result, needing further studies. Bangladesh Journal of Medical Science Vol.18(3) 2019 p.577-585


2015 ◽  
Vol 25 (6) ◽  
Author(s):  
Shohreh Maleknejad ◽  
Ali Mojtahedi ◽  
Afshin Safaei-Asl ◽  
Zeinab Taghavi ◽  
Ehsan Kazemnejad

2020 ◽  
Author(s):  
zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  

Abstract Background: 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 CagA 3’ variable region. 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, and their association with gastroduodenal diseases.Methods: A total of 515 H. pylori isolates from patients in 14 different geographical regions of China were collected and the genomic DNA was extracted. The 3’ variable region of the cagA was amplified by polymerase chain reaction (PCR) and then followed by DNA sequencing, and the amino acid sequences were analyzed with MEGA 7.0 software.Results: A total of 503 (97.7%) H. pylori isolates were cagA-positive and 1,587 EPIYA motifs were obtained, 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 were East Asian type, most of them were ABD subtype (82.1%). Only 22 strains were Western type, including types AC, ABC, ABCC and ABCCCC. 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 isolates are of the CagA-ABD subtype and its presence was associated with gastroduodenal disease. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.


Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 104 ◽  
Author(s):  
Ramsés Dávila-Collado ◽  
Oscar Jarquín-Durán ◽  
Le Thanh Dong ◽  
J. Luis Espinoza

Epstein–Barr virus (EBV) and Helicobacter pylori (H. pylori) are two pathogens associated with the development of various human cancers. The coexistence of both microorganisms in gastric cancer specimens has been increasingly reported, suggesting that crosstalk of both pathogens may be implicated in the carcinogenesis process. Considering that chronic inflammation is an initial step in the development of several cancers, including gastric cancer, we conducted a systematic review to comprehensively evaluate publications in which EBV and H. pylori co-infection has been documented in patients with non-malignant gastroduodenal disorders (NMGDs), including gastritis, peptic ulcer disease (PUD), and dyspepsia. We searched the PubMed database up to August 2019, as well as publication references and, among the nine studies that met the inclusion criteria, we identified six studies assessing EBV infection directly in gastric tissues (total 949 patients) and three studies in which EBV infection status was determined by serological methods (total 662 patients). Due to the substantial methodological and clinical heterogeneity among studies identified, we could not conduct a meta-analysis. The overall prevalence of EBV + H. pylori co-infection in NMGDs was 34% (range 1.8% to 60%). A higher co-infection rate (EBV + H. pylori) was reported in studies in which EBV was documented by serological methods in comparison with studies in which EBV infection was directly assessed in gastric specimens. The majority of these studies were conducted in Latin-America and India, with most of them comparing NMGDs with gastric cancer, but there were no studies comparing the co-infection rate in NMGDs with that in asymptomatic individuals. In comparison with gastritis caused by only one of these pathogens, EBV + H. pylori co-infection was associated with increased severity of gastric inflammation. In conclusion, only relatively small studies testing EBV and H. pylori co-infection in NMGDs have been published to date and the variable report results are likely influenced by geographic factors and detection methods.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1163 ◽  
Author(s):  
Pachathundikandi ◽  
Gutiérrez-Escobar ◽  
Tegtmeyer

The gastric pathogen and carcinogen Helicobacter pylori (H. pylori) encodes a type IV secretion system for translocation of the effector protein CagA into host cells. Injected CagA becomes tyrosine-phosphorylated at the five amino acid residue Glutamate-Proline- Isoleucine-Tyrosine-Alanine (EPIYA)-sequence motifs. These phosphorylated EPIYA-sites represent recognition motifs for binding of multiple host factors, which then manipulate signaling pathways to trigger gastric disease. Thus, efficient detection of single phosphorylated EPIYA-motifs in CagA is required. Detection of phospho-CagA is primarily performed using commercial pan-phosphotyrosine antibodies. However, those antibodies were originally generated to recognize many phosphotyrosines in various mammalian proteins and are not optimized for use in bacteria. To address this important limitation, we synthesized 11-mer phospho- and non-phospho-peptides from EPIYA-motifs A, B, and C, and produced three phospho-specific and three non-phospho-specific rabbit polyclonal CagA antibodies. These antibodies specifically recognized the corresponding phosphorylated and non-phosphorylated EPIYA-motifs, while the EPIYA-C antibodies also recognized the related East-Asian EPIYA-D motif. Otherwise, no cross-reactivity of the antibodies among EPIYAs was observed. Western blotting demonstrated that each EPIYA-motif can be predominantly phosphorylated during H. pylori infection. This represents the first complete set of phospho-specific antibodies for an effector protein in bacteria, providing useful tools to gather information for the categorization of CagA phosphorylation, cancer signaling, and gastric disease progression.


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