Differences in antibody levels to H. pylori virulence factors VacA and CagA among African Americans and whites in the Southeast USA

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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Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma

Pathogens ◽

10.3390/pathogens10030331 ◽

2021 ◽

Vol 10 (3) ◽

pp. 331

Author(s):

Montserrat Palau ◽

Núria Piqué ◽

M. José Ramírez-Lázaro ◽

Sergio Lario ◽

Xavier Calvet ◽

...

Keyword(s):

Helicobacter Pylori ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Virulence Factors ◽

Outer Membrane Proteins ◽

Whole Genome ◽

Flagellar Biosynthesis ◽

H Pylori ◽

Restriction Modification

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

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A Novel Line Immunoassay Based on Recombinant Virulence Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00433-13 ◽

2013 ◽

Vol 20 (11) ◽

pp. 1703-1710 ◽

Cited By ~ 26

Author(s):

Luca Formichella ◽

Laura Romberg ◽

Christian Bolz ◽

Michael Vieth ◽

Michael Geppert ◽

...

Keyword(s):

Helicobacter Pylori ◽

Immune Responses ◽

Virulence Factors ◽

Gastrointestinal Disease ◽

Individual Risk ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Serologic Test ◽

Content Type ◽

H Pylori

ABSTRACTHelicobacter pyloricolonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome.H. pylorivirulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to importantH. pylorivirulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed inEscherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) wereH. pylorinegative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), therecomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, therecomLine assay provides a valuable tool for the diagnosis ofH. pyloriinfection.

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Prevalence of vacA, cagA, and iceA Virulence Factors of Helicobacter Pylori Isolated from Gastro-duodenal Patients

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2020.14.1.592 ◽

2020 ◽

Vol 14 (1) ◽

pp. 72-79

Author(s):

Ahmed Husham Salman ◽

Aumed Arshad Hawezy

Keyword(s):

Helicobacter Pylori ◽

Virulence Factors ◽

Virulence Genes ◽

Gastric Lymphoma ◽

Signs And Symptoms ◽

Molecular Technique ◽

Peptic Ulcers ◽

Back Ground ◽

H Pylori ◽

Pcr Test

Back ground: Helicobacter pylori are bacteria colonize in the human epithelial cells of the gastrointestinal tract. Its infection causes different diseases, including chronic gastritis, peptic ulcers, gastric lymphoma and adenocarcinoma. H. pylori have many virulence factors attributing in one or more biological functions. Objective: Detecting the prevalence of virulence factor genes vacA, cagA, iceA among strain of H. pylori using molecular technique (PCR). Materials and methods: Sixty patients (27 male and 33 female), aged 18 and above included in the present study who showed signs and symptoms of H. pylori, and undergo endoscopy between period of November 2019 and February 2020. RUT and PCR test done to detect the presence of H. pylori infection, also PCR used to detect the three virulence factors. Results: Result showed that 44 patients, 21 (47.7%) male and 23 (52.3%) female were detected as positive H. pylori infections, among them 13 (29.5%) above 50 years, and 31 (70.4%) were below 50 years. While prevalence of the virulence factors vacA, cagA, and iceA were (100%), (84.1%), and (34.1%) respectively. Conclusion: It can be concluded that the frequency and prevalence of these genes are differed and showed significant differences among them. Also, PCR test is sensitive and accurate for detection of H. pylori virulence genes.

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New Insights into Bioactive Compounds from the Medicinal Plant Spathodea campanulata P. Beauv. and Their Activity against Helicobacter pylori

Antibiotics ◽

10.3390/antibiotics9050258 ◽

2020 ◽

Vol 9 (5) ◽

pp. 258

Author(s):

Corinne Raïssa Ngnameko ◽

Lucia Marchetti ◽

Barbara Zambelli ◽

Antonio Quotadamo ◽

Davide Roncarati ◽

...

Keyword(s):

Helicobacter Pylori ◽

Medicinal Plant ◽

Virulence Factors ◽

Crude Extract ◽

High Performance ◽

High Resolution Mass Spectrometry ◽

High Performance Liquid Chromatographic ◽

Chemical Components ◽

Interesting Compound ◽

H Pylori

The medicinal plant Spathodea campanulata P. Beauv. (Bignoniaceae) has been traditionally applied for the prevention and treatment of diseases of the kidney and urinary system, the skin, the gastrointestinal tract, and inflammation in general. The present work shows for the first time how chemical components from this plant inhibit Helicobacter pylori growth by urease inhibition and modulation of virulence factors. The crude extract and the main fractions of S. campanulata bark were tested on H. pylori isolated strains and the active ones were further fractionated. Fractions and sub-fractions of the plant crude extract were characterized by ultra-high-performance liquid chromatographic tandem high resolution-mass spectrometry detection (UHPLC-HRMS). Several phenolics and triterpenoids were identified. Among the sub-fractions obtained, SB2 showed the capacity to inhibit H. pylori urease in a heterologous bacterial model. One additional sub-fraction (SE3) was able to simultaneously modulate the expression of two adhesins (HopZ and BabA) and one cytotoxin (CagA). The flavonol kaempferol was identified as the most interesting compound that deserves further investigation as a new hit for its capacity to modulate H. pylori virulence factors.

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Vitamin B6 Is Required for Full Motility and Virulence in Helicobacter pylori

mBio ◽

10.1128/mbio.00112-10 ◽

2010 ◽

Vol 1 (3) ◽

Cited By ~ 25

Author(s):

Alexandra Grubman ◽

Alexandra Phillips ◽

Marie Thibonnier ◽

Maria Kaparakis-Liaskos ◽

Chad Johnson ◽

...

Keyword(s):

Gene Expression ◽

Helicobacter Pylori ◽

Virulence Factors ◽

Bacterial Pathogens ◽

Therapeutic Targets ◽

Vitamin B ◽

Human Pathogens ◽

Chronic Colonization ◽

H Pylori

ABSTRACTDespite recent advances in our understanding of howHelicobacter pyloricauses disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors inH. pylori, we generated low-infectivity variants of a mouse-colonizingH. pyloristrain using the classical technique ofin vitroattenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of theEscherichia colivitamin B6biosynthesis enzymes PdxA and PdxJ. Functional complementation studies withE. coliconfirmedH. pyloriPdxA and PdxJ to bebona fidehomologs of vitamin B6biosynthesis enzymes. Importantly,H. pyloriPdxA was required for optimal growthin vitroand was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B6is necessary for the synthesis of glycosylated flagella and for flagellum-based motility inH. pylori. Thus, for the first time, we identify vitamin B6biosynthesis enzymes as novel virulence factors in bacteria. Interestingly,pdxAandpdxJorthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.IMPORTANCEApproximately half of the world’s population is infected withH. pylori, yet howH. pyloribacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors forH. pylori. These genes encoded enzymes involved in the synthesis of vitamin B6, an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B6biosynthesis in human pathogens. We showed that mutantH. pyloribacteria lacking an enzyme involved inde novovitamin B6biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B6biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.

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Special Issue “H. pylori Virulence Factors in the Induction of Gastric Cancer”

Toxins ◽

10.3390/toxins10050176 ◽

2018 ◽

Vol 10 (5) ◽

pp. 176 ◽

Cited By ~ 1

Author(s):

Jean Crabtree ◽

Silja Wessler

Keyword(s):

Gastric Cancer ◽

Virulence Factors ◽

Special Issue ◽

H Pylori

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H. pylori-induced higher C-reactive protein in obese African Americans

Artery Research ◽

10.1016/j.artres.2009.01.004 ◽

2009 ◽

Vol 3 (1) ◽

pp. 39 ◽

Cited By ~ 2

Author(s):

Nuzhat R. Siddiqui ◽

W. Timothy Garvey ◽

Mohammad A. Khaled

Keyword(s):

African Americans ◽

C Reactive Protein ◽

Reactive Protein ◽

H Pylori

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A review of the possible bacterial determinants of clinical outcome inHelicobacter pyloriinfection

Canadian Journal of Microbiology ◽

10.1139/w97-143 ◽

1998 ◽

Vol 44 (3) ◽

pp. 201-210 ◽

Cited By ~ 5

Author(s):

Carlo A Fallone ◽

Alan N Barkun ◽

Markus U Göttke ◽

Robin N Beech

Keyword(s):

Helicobacter Pylori ◽

Clinical Outcome ◽

Virulence Factors ◽

Bacterial Virulence ◽

Disease Outcome ◽

Future Research ◽

Susceptible Host ◽

Ulcer Disease ◽

Increased Risk ◽

H Pylori

Helicobacter pylori is present in 40-60% of the population and approximately 10-20% of these infected individuals suffer from a H. pylori associated disease such as peptic ulcer disease or gastric cancer. This article reviews the potential bacterial determinants responsible for and markers predictive of both the acquisition of H. pylori infection and subsequent clinical outcome; i.e., asymptomatic infection or disease. The acquisition of H. pylori infection depends on exposure (hence the increased risk in lower socioeconomic groups and developing nations) to viable bacteria with at least a functional urease gene in a susceptible host. Once infection occurs, bacterial virulence factors, including the vacuolating cytotoxin, and genes of the cag pathogenicity island, as well as nonbacterial factors may determine disease outcome. Future research is being directed at discovering other bacterial virulence factors responsible for the different clinical outcomes of H. pylori infection. This will be greatly enhanced by the recent release of the complete genome sequence of H. pylori. The determination of the relative importance of each of these recognized and other as yet unrecognized factors responsible for disease outcome will assist in the appropriate targeting of patients in the treatment of H. pylori infection.Key words: Helicobacter pylori, genetics, virulence, bacterial.

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Immunoglobulin G Antibody against Helicobacter pylori: Clinical Implications of Levels Found in Serum

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.5.1044-1048.2002 ◽

2002 ◽

Vol 9 (5) ◽

pp. 1044-1048 ◽

Cited By ~ 2

Author(s):

Tseng-Shing Chen ◽

Fen-Yau Li ◽

Full-Young Chang ◽

Shou-Dong Lee

Keyword(s):

Helicobacter Pylori ◽

Chronic Gastritis ◽

Predictive Value ◽

Linear Regression Analysis ◽

Serum Antibody ◽

Quantitative Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Multivariate Linear Regression Analysis ◽

H Pylori ◽

Antibody Levels

ABSTRACT The clinical significance of high levels of antibody against Helicobacter pylori is still unclear. We sought to evaluate whether the serum antibody levels could predict the presence of macroscopic gastroduodenal disease, to identify factors that correlate with antibody levels in a multivariate context, and to determine the predictive value of antibody levels for diagnosing H. pylori infection. The grades of gastritis and density of H. pylori colonization were scored separately using the updated Sydney system for antral and body mucosa. An enzyme-linked immunosorbent assay (ELISA) for the quantitative detection in serum of IgG antibodies to H. pylori was performed. Of the 170 dyspeptic patients, 105 (62%) had H. pylori infection. There was no difference in antibody levels among endoscopic findings of normal mucosa, chronic gastritis, and duodenal ulcer. On multivariate linear regression analysis, the status of H. pylori infection, mononuclear cell infiltration of body mucosa, and age correlated with antibody levels. The negative predictive value for antibody levels of <30 U/ml is 94%, and the positive predictive value of antibody levels of >70 U/ml is 98%. We conclude that serum antibody levels do not predict the severity of gastroduodenal diseases or the density of H. pylori colonization in H. pylori-infected dyspeptic patients. Higher levels are associated with the presence of H. pylori infection, the chronic gastritis score of the corpus, and older age. Setting a gray zone is necessary for ELISA, since the accuracy in this zone does not allow a precise determination of H. pylori status.

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