Relationship between J-Western CagA subtype and the vacA m2 region of Helicobacter pylori.
Ontology highlight
ABSTRACT:
SUBMITTER: Shiota S
PROVIDER: S-EPMC2916575 | biostudies-literature | 2010 Aug
REPOSITORIES: biostudies-literature
Publications
Relationship between J-Western CagA subtype and the vacA m2 region of Helicobacter pylori.
Shiota Seiji S Matsunari Osamu O Yamaoka Yoshio Y
Journal of clinical microbiology 20100602 8
Similar Datasets
Project description:The vacuolating cytotoxin and the cytotoxin-associated protein, encoded by vacA and cagA, respectively, are important virulence determinants of Helicobacter pylori. Sixty-five H. pylori strains were isolated from dyspeptic patients (19 with peptic ulcer disease, 43 with chronic gastritis, and 3 with gastric cancer) and studied for differences in the vacA and cagA genes and their relationship to VacA and CagA expression, cytotoxin activity, and the clinical outcome of infection. By PCR, fifty-four (83.1%) of 65 strains had the vacA signal sequence genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the vacA middle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%) strains, respectively. The combinations s1-m2 (31 [47.7%]) and s1-m1 (23 [35.4%]) occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the combination s2-m1 was found. All 19 patients with peptic ulcers harbored type s1 strains, in contrast to 32 (74.4%) of 43 patients with gastritis (P = 0.02). The vacA genotype s1 was associated with the presence of cagA (P < 0.0001), VacA expression (P < 0.0001), and cytotoxin activity (P = 0.003). The cagA gene was detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of 19 ulcer patients and 29 (67.4%) of 43 patients with gastritis (P = 0.17). The vacA genotypes of German H. pylori isolates are identical to those previously reported. H. pylori strains of vacA type s1 are associated with the occurrence of peptic ulceration and the presence of cagA, cytotoxin activity, and VacA expression.
| S-EPMC104665 | biostudies-literature
Project description:There is continuing interest in identifying Helicobacter pylori virulence factors that might predict the risk for symptomatic clinical outcomes. It has been proposed that iceA and cagA genes are such markers and can identify patients with peptic ulcers. We compared H. pylori isolates from four countries, looking at the cagA and vacA genotypes, iceA alleles, and presentation of the infection. We used PCR to examine iceA, vacA, and cagA status of 424 H. pylori isolates obtained from patients with different clinical presentations (peptic ulcer, gastric cancer, and atrophic gastritis). The H. pylori isolates examined included 107 strains from Bogota, Colombia, 70 from Houston, Tex., 135 from Seoul, Korea, and 112 from Kyoto, Japan. The predominant genotype differed among countries: the cagA-positive iceA1 vacA s1c-m1 genotype was predominant in Japan and Korea, the cagA-positive iceA2 vacA s1b-m1 genotype was predominant in the United States, and the cagA-positive iceA2 vacA s1a-m1 genotype was predominant in Colombia. There was no association between the iceA, vacA, or cagA status and clinical outcome in patients in the countries studied. iceA status shows considerable geographic differences, and neither iceA nor combinations of iceA, vacA, and cagA were helpful in predicting the clinical presentation of an H. pylori infection.
| S-EPMC85136 | biostudies-literature
Project description:Background and aimSeveral biological and epidemiological studies support a relationship between smoking and Helicobacter pylori (H. pylori) to increase the risk of pathology. However, there have been few studies on the potential synergistic association between specific cagA and vacA virulence factors and smoking in patients infected by Helicobacter pylori. We studied the relationship between smoking and cagA, vacA i1 virulence factors and bacterial load in H. pylori infected patients.MethodsBiopsies of the gastric corpus and antrum from 155 consecutive patients in whom there was clinical suspicion of infection by H. pylori were processed. In 106 patients H. pylori infection was detected. Molecular methods were used to quantify the number of microorganisms and presence of cagA and vacA i1 genes. A standardized questionnaire was used to obtain patients' clinical data and lifestyle variables, including tobacco and alcohol consumption. Adjusted Odds Ratios (ORadjusted) were estimated by unconditional logistic regression.ResultscagA was significantly associated with active-smoking at endoscope: ORadjusted 4.52. Evidence of association was found for vacA i1 (ORadjusted 3.15). Bacterial load was higher in active-smokers, although these differences did not yield statistical significance (median of 262.2 versus 79.4 copies of H. pylori per cell).ConclusionsThe association between smoking and a higher risk of being infected by a virulent bacterial population and with higher bacterial load, support a complex interaction between H. pylori infection and environmental factors.
| S-EPMC4368826 | biostudies-literature
Project description:The issue of drug resistance of Helicobacter pylori is becoming increasingly serious. To analyze the correlation between the cagA and vacA genotypes of H. pylori strains and their resistance to metronidazole, levofloxacin, and clarithromycin in patients in Xi'an, we studied 117 H. pylori strains isolated from patients in Xi'an. Antibiotic susceptibility testing of H. pylori was performed. The cagA and vacA genotypes were investigated using PCR. Among 117 strains of H. pylori, the rate of detection of cagA was 91.45% (107/117), among which the detection rate of East Asian-type cagA was 85.05% (91/107) and that of Western-type cagA was 14.95% (16/107). There were only two genotypes of vacA: s1m1 and s1m2. The detection rate of vacAs1m1 was 47.01% (55/117) and that of vacAs1m2 was 52.99% (62/117). The dominant strains in Xi'an were cagA + vacAs1m2 strains. The metronidazole resistance rate of vacAs1m2 H. pylori strains was significantly higher than that of vacAs1m1 H. pylori strains (91.94% vs. 69.09%, P = 0.002). The levofloxacin resistance rate of Western-type cagA strains was significantly higher than that of East Asian-type cagA strains (56.25% vs. 20.88%, P = 0.004). The metronidazole resistance rate of cagA + vacAs1m2 H. pylori strains was significantly higher than that of cagA + vacAs1m1 H. pylori strains (91.23% vs. 66.00%, P = 0.001). Our results showed that Western-type cagA strains were more likely to develop levofloxacin resistance than East Asian-type cagA strains. VacAs1m2 strains were more prone to metronidazole resistance than vacAs1m1 strains.
| S-EPMC10689652 | biostudies-literature
Project description: Not available
| S-EPMC86851 | biostudies-literature
Project description:The diversity of the cytotoxin-associated gene (cagA) of Helicobacter pylori was analyzed in 45 isolates obtained from nine countries. We examined variation in the 5' end of the cagA open reading frame as determined by PCR and sequencing. Phylogenetic analysis revealed the existence of at least two distinct types of cagA. One variant (cagA1) was found exclusively in strains from Europe, the United States, and Australia, whereas a novel variant (cagA2) was found in strains from East Asia. The greatest diversity between cagA1 and cagA2 was found in the first 20 amino acids of the cagA open reading frame, where several consistent insertions or deletions were observed. Additional cagA sequence variants that could be classified as separate subtypes were found in two of three Peruvian and in five of seven U.S. strains tested. The calculated isoelectric point of the first 154 amino acids of the cagA1 variants (7.52 +/- 1.54) was significantly higher than that of the first 154 amino acids of the cagA2 variants (5.61 +/- 0.94; P < 0.001). Most cagA2 strains contained vacA subtype s1c (P < 0.001), and in vacA m1 strains cagA1 was more frequently observed than cagA2. These results show the epidemiological relationship between cagA and vacA at the subtype level and indicate the existence of distinct H. pylori lineages that are not uniformly distributed over the globe.
| S-EPMC85143 | biostudies-literature
Project description:Helicobacter pylori, which is involved in the pathogenesis of gastroduodenal disease, produces CagA and VacA as major virulence factors. CagA is classified into East Asian and Western types based on the number and sequences of its Glu-Pro-Ile-Tyr-Ala motifs. The vacA gene has three polymorphic regions: the signal (s), intermediate (i), and middle (m) regions. The lowest gastric cancer mortality rate is seen in Okinawa. On the Japanese mainland (Honshu), most H. pylori produce s1/m1-VacA, which exhibits strong toxicity, and East Asian-type CagA. However, the H. pylori detected in Okinawa produces s1/m2-VacA, which exhibits weak toxicity, or s2/m2-VacA, which is non-toxic, and Western-type CagA. Studies about the i-region of vacA have been performed around the world, but there have been few such studies in Japan. Therefore, the aim of this study was to assess the relationships between the clinical outcomes of H. pylori infections in Okinawa, vacA (especially the i-region genotype), and cagA. H. pylori strains that were collected from patients with gastric cancer or gastric ulcers in Okinawa only produced the i1-type VacA virulence factor. The vacuolating cytotoxin activity of i1-type VacA was stronger than that of i2-type VacA, suggesting that the i-region genotype of vacA is closely associated with vacuolating cytotoxin activity. These results indicate that the i-region genotype of vacA is a useful marker of both H. pylori virulence and the clinical outcomes of H. pylori infections in Okinawa, Japan.
| S-EPMC5826021 | biostudies-literature
Project description:Helicobacter pylori (H. pylori) is the causative agent of gastric cancer, making it the only bacterium to be recognized as a Class I carcinogen by the World Health Organization. The virulence factor cytotoxin associated gene A (CagA) is a known oncoprotein that contributes to the development of gastric cancer. The other major virulence factor vacuolating cytotoxin A (VacA), disrupts endolysosomal vesicular trafficking and impairs the autophagy pathway. Studies indicate that there is a functional interplay between these virulence factors by unknown mechanisms. We show that in the absence of VacA, both host-cell autophagy and the proteasome degrade CagA during infection with H. pylori. In the presence of VacA, CagA accumulates in gastric epithelial cells. However, VacA does not affect proteasome function during infection with H. pylori suggesting that VacA-disrupted autophagy is the predominant means by which CagA accumulates. Our studies support a model where in the presence of VacA, CagA accumulates in dysfunctional autophagosomes providing a possible explanation for the functional interplay of VacA and CagA.
| S-EPMC6328614 | biostudies-literature
Project description:Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer. Many studies of H. pylori virulence markers in children have the bias that symptomatic subjects are selected for endoscopy, and these children may harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA alleles in stool DNA samples of healthy Colombian children residing in an area with high incidence of gastric cancer, to avoid selection bias resulting from endoscopy.H. pylori status of 86 asymptomatic children was assessed by (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA genes were amplified from stool DNA samples and sequenced.UBT was positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples, which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1 genotypes (p < 0.0001).Using stool DNA samples, virulence markers of H. pylori were successfully genotyped in a high percentage of the asymptomatic infected children, revealing a high prevalence of genotypes associated with virulence. Type I hopQ alleles were associated with the presence of cagA and the vacA s1 genotype.
| S-EPMC3305281 | biostudies-literature
Project description:BackgroundH. pylori virulence factors, especially vacA and cagA are important in gastroduodenal disease pathogenesis and affect cure rates. This meta-analysis aimed to clarify the association between vacA or cagA status and eradication outcome of H. pylori infection.MethodsA literature search was performed using electronic databases to identify studies. Twenty-six prospective studies were determined eligible. Meta-analytical techniques were conducted to calculate eradication rates and pooled relative ratios (RR).ResultsThe eradication rate was greater approximately 10% in vacA s1 compared with vacA s2 infected patients, and the pooled RR was 1.164 (95%CI: 1.040-1.303, P = 0.008). A significant association existed between vacA s1 and higher eradication rates in Europe (RR: 1.203, 95%CI: 1.003-1.442, P = 0.046) and Asia (RR: 1.187, 95%CI: 1.028-1.371, P = 0.020), in triple therapy patients (RR: 1.175, 95%CI: 1.012-1.365, P = 0.035). Eradication rates were similar for vacA m1 and m2 genotypes (RR: 0.981, 95%CI: 0.891-1.080, P = 0.690), whereas they were higher by approximately 8% in cagA-positive compared with cagA-negative infected patients, with a pooled RR of 1.094 (95%CI: 1.025-1.168, P = 0.007). A significant association existed between cagA-positive and increased eradication rates in Europe (RR: 1.138, 95%CI: 1.000-1.295, P = 0.049) and Asia (RR: 1.118, 95%CI: 1.051-1.190, P<0.001), in using PCR (RR: 1.232, 95%CI: 1.142-1.329, P<0.001) and protein chips (RR: 1.200, 95%CI: 1.060-1.359, P = 0.004), in triple therapy patients (RR: 1.090, 95%CI: 1.006-1.181, P = 0.034).ConclusionsEvidence indicates that infection with vacA s1, cagA-positive strains, but not vacA s2, cagA-negative, is more conducive to H. pylori eradication.
| S-EPMC5426689 | biostudies-literature