Prevalence of Helicobacter pylori vacA,cagA,dupA and oipA Genotypes in Patients with Gastric Disease

Gastric diseases such as chronic gastritis and gastric cancer are most commonly caused by virulence factors of Helicobacter pylori (H. pylori), such as the vacA, cagA, dupA and oipA genes. Therefore, this study investigated the prevalence and the combination of these virulence factors from patients with gastric diseases. The endoscopic biopsies were obtained from 516 patients with gastric symptoms, 101 of which were from patients with normal gastric tissue, 365 of which were from patients with chronic gastritis, and 50 of which were from patients with gastric cancer. H. pylori and the virulence factors were detected by PCR. The oipA gene exhibited an increased risk for chronic gastritis (p = 0.0296), and the vacA gene demonstrated a risk for gastric cancer from chronic gastritis (p = 0.0002). Based on the combination of the virulence factors, cagA, vacA, dupA and oipA genes exhibited a high prevalence in patients with chronic gastritis and gastric cancer. The cagA+/dupA+ genotype demonstrated a significant correlation in patients with normal gastric mucosa (p = 0.0278). In the chronic gastritis group, a significant association was observed between the cagA+ and the vacA s1m1 genotypes (p cagA+/dupA+ genotypes (p = 0.0183), the dupA+/oipA+ genotypes (p cagA, vacA, dupA, and oipA genes, which contributed to the risk of developing gastroduodenal diseases. Furthermore, this is the first study to reveal a high prevalence of the oipA gene in H. pylori isolates in Brazil.

Helicobacter pylori Virulence Genes cagA, babA2, and vacA Detection in Dyspeptic Patients from Burkina Faso

The diverse clinical presentation of Helicobacter pylori (H. pylori) infection results from the interaction between bacterial virulence, host genetics, socio-demographic and environmental factors. This study aimed to characterize Helicobacter pylori virulence genes and the associated behavioral factors among dyspeptic patients in Burkina Faso. Two hundred and fifty (250) stool samples were collected from patients with dyspepsia seen at health centers in Ouagadougou, Burkina Faso. Bacterial deoxyribonucleic acid (DNA) was extracted using a commercial kit. Virulence genes were detected using conventional multiplex Polymerase Chain Reaction with specific primers. The overall prevalence of Helicobacter pylori of the 250 participants was 91.20%. CagA virulence gene was present among 20.19% of individuals, while babA2 and vacA were detected respectively among 9.65% and 67.54% of the population positive for Helicobacter pylori. Among vacA subtypes, vacAs1 was the most frequent, with 39.04%, followed by vacAi1 (19.74%), vacAi2 (17.54%), and vacAs2 with 10.96%. Regarding vacAm1 and vacAm2, they were less frequent at 6.14% each. “Handwashing three times or less per day” significantly increased the risk of having vacAi2 allele and H. pylori rRNA16s, with p-values of 0.013 and 0.020, respectively. The consumption of non-tap water increases the risk of carrying the cagA virulence gene. Additionally, H. pylori-positive patients living with more than four (4) people in their household had about two times the risk of having the vacAs1 allele. The present study shows the detection of Helicobacter pylori cagA, vacA subtypes, and babA2 by stool a PCR method in Burkina Faso. The strong association between sanitary habits and virulence factors depicts the composite interaction between ecological factors, gastric mucosa, and bacteria. Therefore, the synergic action of these factors should be considered when aiming for bacterial eradication and gastric pathology cure.

Helicobacter pylori vac A genotype is a predominant determinant of immune response to Helicobacter pylori CagA

To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. METHODSSystematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. RESULTSThirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. CONCLUSIONSerological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

Restoration of Mitochondrial Structure and Function within Helicobacter pylori VacA Intoxicated Cells

The Helicobacter pylori vacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has been reported to alter overall cellular metabolism, there is little known about the consequences of extended exposure to the toxin. Here, we describe studies to address this gap in knowledge, which have revealed that mitochondrial dysfunction and fragmentation are followed by a time-dependent recovery of mitochondrial structure, mitochondrial transmembrane potential, and cellular ATP levels. Cells exposed to VacA also initially demonstrated a reduction in oxidative phosphorylation, as well as increase in compensatory aerobic glycolysis. These metabolic alterations were reversed in cells with limited toxin exposure, congruent with the recovery of mitochondrial transmembrane potential and the absence of cytochrome c release from the mitochondria. Taken together, these results are consistent with a model that mitochondrial structure and function are restored in VacA-intoxicated cells.

Helicobacter pylori in dental plaque and stomach of patients from Northern Brazil

AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.

Molecular cross-talk between Helicobacter pylori and human gastric mucosa

Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.

Diversity of Helicobacter pylori genotypes in Iranian patients with different gastroduodenal disorders

AIM:To investigate the diversity of Helicobacter pylori(H.pylori)genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders.METHODS:Isolates of H.pylori from patients with different gastroduodenal disorders were analyzed after culture and identification by phenotypic and genotypic methods.Genomic DNA was extracted with the QIAamp DNA mini kit(Qiagen,Germany).After DNA extraction,genotyping was done for cagA,vacA(s and m regions),iceA(iceA1,iceA2)and babA with specific primers for each allele using polymerase chain reaction(PCR).All patients’pathologic and clinical data and their relation with known genotypes were analyzed by using SPSS version 19.0 software.2test and Fisher’s exact test were used to assess relationships between categorical variables.The level of statistical significance was set at P<0.05.RESULTS:A total of 71 isolates from 177 patients with different gastroduodenal disorders were obtained.Based on analysis of the cagA gene(positive or negative),vacA s-region(s1or s2),vacA m-region(m1or m2),iceA allelic type(iceA1and iceA2)and babA gene(positive or negative),twenty different genotypic combinations were recognized.The prevalence of cagA,vacA s1,vacA s2,vacA m1,vacA m2,iceA1,iceA2,iceA1+iceA2and babA were 62%,78.9%,19.7%,21.1%,78.9%,15.5%,22.5%,40.8%and 95.8%,respectively.Interestingly,evaluation of PCR results for cagA in 6 patients showed simultaneous existence of cagA variants according to their size diversities that proposed mixed infection in these patients.The most prevalent genotype in cagA-positive isolates was cagA+/vacAs1m2/iceA1+A2/babA+and in cagA-negative isolates was cagA-/vacAs1m2/iceA-/babA+.There were no relationships between the studied genes and histo-pathological findings(H.pylori density,neutrophil activity,lymphoid aggregation in lamina propria and glandular atrophy).The strains which carry cagA,vacAs1/m1,iceA2and babA genes showed significant associations with severe active chronic gastritis(P=0.011,0.025,0.020 and 0.031,respectively).The vacAs1genotype had significant correlation with the presence of the cagA gene(P=0.013).Also,babA genotype showed associations with cagA(P=0.024).In the combined genotypes,only cagA+/vacAs1m1/iceA2/babA+genotype showed correlation with severe active chronic gastritis(P=0.025).CONCLUSION:This genotyping panel can be a useful tool for detection of virulent H.pylori isolates and can provide valuable guidance for prediction of the clinical outcomes.

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori(H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype Helico DR assay. cag A and vac A genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5%(n = 53/105), 78.3%(n = 47/60) and 60.6%(n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2%(n = 16/105) and 28.3%(n = 17/60) and 20%(n = 33/165), respectively. Resistance to both antibiotics was 12.4%(n = 13/105) in treatment-na?ve patients, 25%(n = 15/60) in those previously treated and 17%(n = 28/165) overall. A cag A-positive genotype was detected in 22.4%(n = 37/165) of patient samples. The dominant vac A genotype was S1/M2 at 44.8%(n = 74/165), followed by S2/M2 at 26.7%(n = 44/165), S1/M1 at 23.6%(n = 39/165) and S2/M1 at 4.8%(n = 8/165). Primary clarithromycin resistance was significantly lower in cag A-positive strains than in cag A-negative strains [32%(n = 8/25) vs 56.3%(n = 45/80); P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vac A s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vac A s2 genotype, [41%(n = 32/78) vs 77.8%(n = 21/27); P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status.CONCLUSION Genotypic H. pylori clarithromycin resistance is high and cag A-negative strains are dominant in our population. Less virulent(cag A-negative and vac A S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

Helicobacter pylori and gastric cancer in the Middle East: A new enigma?

The Middle East is the home of ethnic groups from three main backgrounds: Semitic (Arabs and Jews), Indo-European (Persians and Kurdish) and Turkic (Turkish and Turkmens). Its geographic location, which has been under continuous influences from Asia, Europe and Africa, has made it an ideal site for epidemiological studies on Helicobacter pylori (H. pylori) infection and genotyping. The gastric cancer rate differs in this region from very high in Iran (26.1/105) to low in Israel (12.5/105) and very low in Egypt (3.4/105). Epidemiological studies showed that the prevalence of H. pylori is almost similar in those countries with a high level of infection in childhood. Importantly, the frequency of vacA s1 and m1 regions and cagA+ genotypes were higher in non Semitic populations who inhabit the North than Semitic populations, the inhabitants of Southern parts of the Middle East. H. pylori infection prevalence, distribution pattern of virulence factors, diet and smoking could not have explained the difference in cancer rate. This reflects the multifactorial aetiology of gastric cancer and suggests that H. pylori infection does not always directly correlate with the risk for gastrointestinal disease, such as gastric cancer. Further detailed investigations and international comparative studies of each risk factor needto be performed to investigate whether this represents a true enigma.

Distribution of Helicobacter pylori in north China

AIM: To compare the distribution of virulence-associatedgenotypes of Helicobacter pylori(H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vac A, and iceA.RESULTS: In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. CONCLUSION: There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.

Genomic variability of Helicobacter pylori isolates of gastric regions from two Colombian populations

AIMTo compare the genomic variability and the multiple colonization of Helicobacter pylori (H. pylori) in patients with chronic gastritis from two Colombian populations with contrast in the risk of developing gastric cancer (GC): T&#x000fa;querres-Nari&#x000f1;o (High risk) and Tumaco-Nari&#x000f1;o (Low risk).METHODSFour hundred and nine patients from both genders with dyspeptic symptoms were studied. Seventy-two patients were included in whom H. pylori was isolated from three anatomic regions of the gastric mucosa, (31/206) of the high risk population of GC (T&#x000fa;querres) and (41/203) of the low risk population of GC (Tumaco). The isolates were genotyped by PCR-RAPD. Genetic diversity between the isolates was evaluated by conglomerates analysis and multiple correspondence analyses.RESULTSThe proportion of virulent genotypes of H. pylori was 99% in T&#x000fa;querres and 94% in Tumaco. The coefficient of similarity of Nei-Li showed greater genetic diversity among isolates of T&#x000fa;querres (0.13) than those of Tumaco (0.07). After adjusting by age, gender and type of gastritis, the multiple colonization was 1.7 times more frequent in T&#x000fa;querres than in Tumaco (P = 0.05).CONCLUSIONIn T&#x000fa;querres, high risk of GC there was a greater probability of multiple colonization by H. pylori. From the analysis of the results of the PCR-RAPD, it was found higher genetic variability in the isolates of H. pylori in the population of high risk for the development of GC.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.

幽门螺杆菌cagA、vacA抗体与胃十二指肠疾病的相关性研究

目的 :探讨幽门螺杆菌 (Hp)毒力基因cagA、vacA抗体与胃十二指肠疾病之间的关系。方法 :采用免疫印迹法检测 440例胃十二指肠疾病患者血清中的cagA、vacA抗体。结果 :cagA、vacA抗体在 440例患者中的检出率分别为 73 %、37.0 %。在慢性胃炎 (CG)、十二指肠球部溃疡 (DU)、胃癌 (GC)患者中 ,cagA、vacA抗体的阳性率分别为 62 .9% ,76 .1 %、96 .9%与 33 .0 %、31 .0 %、62 .5 % ;经u检验显示 :慢性胃炎组与十二指肠球部溃疡组比较 ,无明显差异。胃癌组与慢性胃炎组、十二指肠球部溃疡组比较 ,有显著性差异。结论 :本文通过患者血清中Hp抗体 (cagA和vacA)的检测 ,推知其cagA和vacA抗体的表达状况 ,可为胃十二指肠疾病的诊断提供依据 。

幽门螺杆菌及其vacA基因亚型和cagA基因与胃上皮HLA-DR抗原表达的关系

【目的】探讨幽门螺杆菌及其空泡毒素基因 (vacA)亚型、细胞毒素相关基因 (cagA)与胃上皮HLA DR抗原表达间的关系。【方法】①自 39例幽门螺杆菌阳性患者中分离培养出 39株幽门螺杆菌菌株 ,采用PCR方法鉴定 39株菌株的ca gA及vacA亚型 ;②采用HLA DR小鼠抗人单克隆抗体 ,对上述已行cagA及vacA亚型鉴定的幽门螺杆菌阳性患者及 2 2例阴性患者的胃窦活检标本行免疫组化染色。【结果】①幽门螺杆菌阳性患者胃上皮HLA DR表达较阴性患者更显著 ;②幽门螺杆菌定植密度与胃上皮HLA DR抗原表达程度间存在正相关 ;③感染cagA+ 菌株患者较感染cagA-株者胃上皮HLA DR抗原表达更明显 ;④本研究中vacAs1a/m2亚型占 90 % ,故未对不同vacA亚型与胃上皮HLA DR表达间的关系进行统计分析。【结论】①幽门螺杆菌感染可诱导胃上皮HLA DR抗原异常表达 ;②cagA+ 菌株可能通过胃上皮HLA Ⅱ类分子介导而与宿主发生更为密切的相互作用 ,从而较cagA-菌株引起更为显著的胃上皮损伤。

贵阳地区幽门螺杆菌临床分离株中ureA、cagA、vacA、iceA基因的分布及分析

目的了解贵阳地区临床分离的幽门螺杆菌(Hp)的毒力基因ureA、cagA、vacA、iceA的分布特征,探讨不同毒力基因型与上消化道疾病的关系。方法用特异的16SrDNA聚合酶链反应进行临床分离Hp的菌种鉴定,对经过鉴定的152株幽门螺杆菌进行ureA、cagA、vacA、iceA基因及亚型的PCR检测。结果 ureA基因的检出率为100%(152/152),vacA基因的检出率为100%(152/152),vacA基因亚型以s1a-m2型为主,占76.3%(116/152),cagA基因检出率为39.5%(60/152),ieeA1基因检出率36.8%(56/152),iceA2基因检出率为34.2%(52/152),13.2%(20/152)的菌株iceA1和iceA2基因均阳性,不同基因型菌株在慢性胃炎和消化性溃疡中的检出率无统计学意义(P>0.05)。结论贵阳地区幽门螺杆菌毒力基因vacA以s1a-m2型为主,cagA阴性比例高于cagA阳性,不同基因型菌株与消化性疾病间无明显相关性。

CagA^+及VacA^+幽门螺杆菌对克拉霉素的耐药性突变分析

目的分析CagA+及VacA+的幽门螺杆菌(Hp)对克拉霉素耐药与23S rRNA基因点突变的关系。方法采集右江民族医学院附属医院2006~2008年确诊为Hp感染患者的胃窦部黏膜样本进行Hp分离培养和鉴定,PCR扩增CagA+及VacA+基因,E-test进行药敏实验,PCR方法扩增23S rRNA基因,基因测序检测克拉霉素耐药菌株的点突变。结果对克拉霉素耐药的CagA+及VacA+Hp菌株均存在23S rRNA基因v功能区第2144位和第2143位A-G突变,而敏感菌株没有发现该位点突变。结论Hp对克拉霉素耐药的23S rRNA基因A2143G、A2144G点发生突变,与基因分型无关。

幽门螺杆菌vacA和cagA基因全长分子系统发育分析

文章从GenBank中下载所有含有vacA和cagA基因的H.pylori菌株的VacA和CagA全长氨基酸序列,利用ClastalX 2.0和MEGA 5.05软件构建VacA和CagA分子系统发育树,探讨两基因之间的分子系统发育关系和不同聚类群的临床感染结果与基因型特征。结果显示,VacA和CagA具有高度相似的分子系统发育树,并且所有H.pylori菌株在系统发育树中具有相同的分布特点,分别聚类为东亚株群1、2和西方株群3个聚类群。其中东亚株群1患萎缩性胃炎比例较高,vacA基因型以s1c/m1b和s1a/m1b为主,cagA基因型以EPIYA-ABD为主;东亚株群2患十二指肠溃疡的比例较高,vacA基因型以s1c/m2和s1a/m2为主,cagA基因型以EPIYA-AB'C为主;西方株群患十二指肠溃疡和胃炎的比例相当,萎缩性胃炎比例较低,vacA基因型以s1a/m1a和s1b/m1a为主,cagA基因型以EPIYA-AB/B'CC为主。这些结果说明,vacA和cagA基因可能具有共进化的遗传关系;东亚株群1、2和西方株群分别具有不同的vacA和cagA基因亚型,这可能与其临床感染结果密切相关,因此,在进行H.pylori相关性疾病分析时,有必要结合vacA和cagA基因型的亚型做深入分析。

幽门螺杆菌vacA及cagA基因型与胃疾病的关系

目的探讨幽门螺杆菌(Hp)vacA、cagA基因型与胃疾病的关系。方法选取105例胃疾病病人,包括慢性浅表性胃炎(CSG)45例,慢性萎缩性胃炎(CAG)48例,胃癌(GC)12例。于胃窦处取3块胃黏膜,分别进行快速尿素酶反应、病理检查和聚合酶链反应(PCR)。提取胃黏膜基因组DNA,用6对引物检测Hp vacA、cagA基因的表达。结果快速尿素酶反应、病理检查均阳性的标本57例,Hp的阳性率为54.2%(57/105)。Hp vacA s1/m2、s1/m1、s2/m1、s2/m2的阳性率分别为53%(30/57)、18%(10/57)、8%(5/57)、21%(12/57);Hp cagA的阳性率为89%(51/57)。vacA、cagA基因型在CSG、CAG和GC之间差异无显著性(P>0.05)。结论Hp菌株的优势基因亚型为Hp cagA、vacA s1/m2;Hp vacA、cagA基因与特定胃疾病间无显著相关性,不能预示Hp感染的临床结果。

幽门螺杆菌VacA、CagA及BabA蛋白的二级结构和免疫表位预测分析

目的:预测幽门螺杆菌的重要抗原组分VacA、CagA及BabA蛋白的二级结构和B细胞表位。方法:基于序列比对和进化树分析,选择幽门螺杆菌J99作为源菌株,进行相关蛋白质二级结构和免疫表位的预测。应用DNASTAR Protean软件,通过Chou-Fasman和Garnier-Robson方法,预测α螺旋、β折叠、转角以及卷曲结构;通过Jameson-Wolf、Emini、Kyte-Doolittle和Karplus-Schulz方法,分别预测抗原性指数、表面可能性、氨基酸亲水性和柔性区域。结果:VacA和BabA有较多的β折叠,CagA主要由大量α螺旋组成,三者转角或卷曲的构成比例则基本相似。VacA蛋白有5～11、28～31和1 235～1 243等18个优势B细胞表位区段,BabA的优势表位有19～25、41～55和692～702等16个区段;CagA有更多的B细胞表位,主要分布在5～12、40～57及1 154～1 167等30个区段。结论:基本明确了VacA、CagA及BabA蛋白的二级结构特征和B细胞表位区段,为进一步通过动物实验筛选出高效表位奠定了基础。