scholarly journals Riboregulation in the Major Gastric Pathogen Helicobacter pylori

2021 ◽  
Vol 12 ◽  
Author(s):  
Alejandro Tejada-Arranz ◽  
Hilde De Reuse

Helicobacter pylori is a Gram-negative bacterial pathogen that colonizes the stomach of about half of the human population worldwide. Infection by H. pylori is generally acquired during childhood and this bacterium rapidly establishes a persistent colonization. H. pylori causes chronic gastritis that, in some cases, progresses into peptic ulcer disease or adenocarcinoma that is responsible for about 800,000 deaths in the world every year. H. pylori has evolved efficient adaptive strategies to colonize the stomach, a particularly hostile acidic environment. Few transcriptional regulators are encoded by the small H. pylori genome and post-transcriptional regulation has been proposed as a major level of control of gene expression in this pathogen. The transcriptome and transcription start sites (TSSs) of H. pylori strain 26695 have been defined at the genome level. This revealed the existence of a total of 1,907 TSSs among which more than 900 TSSs for non-coding RNAs (ncRNAs) including 60 validated small RNAs (sRNAs) and abundant anti-sense RNAs, few of which have been experimentally validated. An RNA degradosome was shown to play a central role in the control of mRNA and antisense RNA decay in H. pylori. Riboregulation, genetic regulation by RNA, has also been revealed and depends both on antisense RNAs and small RNAs. Known examples will be presented in this review. Antisense RNA regulation was reported for some virulence factors and for several type I toxin antitoxin systems, one of which controls the morphological transition of H. pylori spiral shape to round coccoids. Interestingly, the few documented cases of small RNA-based regulation suggest that their mechanisms do not follow the same rules that were well established in the model organism Escherichia coli. First, the genome of H. pylori encodes none of the two well-described RNA chaperones, Hfq and ProQ that are important for riboregulation in several organisms. Second, some of the reported small RNAs target, through “rheostat”-like mechanisms, repeat-rich stretches in the 5′-untranslated region of genes encoding important virulence factors. In conclusion, there are still many unanswered questions about the extent and underlying mechanisms of riboregulation in H. pylori but recent publications highlighted original mechanisms making this important pathogen an interesting study model.

2013 ◽  
Vol 20 (11) ◽  
pp. 1703-1710 ◽  
Author(s):  
Luca Formichella ◽  
Laura Romberg ◽  
Christian Bolz ◽  
Michael Vieth ◽  
Michael Geppert ◽  
...  

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.


1998 ◽  
Vol 44 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Carlo A Fallone ◽  
Alan N Barkun ◽  
Markus U Göttke ◽  
Robin N Beech

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.


2014 ◽  
Vol 7 ◽  
pp. CGast.S13760 ◽  
Author(s):  
Bruna M. Roesler ◽  
Elizabeth M.A. Rabelo-Gonçalves ◽  
José M.R. Zeitune

Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome.


2016 ◽  
Vol 4 (3) ◽  
pp. 352-358
Author(s):  
Mohamed E. Rashed ◽  
Amer M.M. ◽  
Mostafa Elnakeeb ◽  
Waleed Saeed Omer

Helicobacter pylori infection is tremendous medical burden especially in developing countries. Various immunological tests are available for diagnosis of H. pylori infection. Western blot method is proven to be promising for Precise, easy reading, sensitive and specific detection of H. pylori infections, besides it also permits the detection for the different virulence factors of CagA / VacA positive strains (type I). The objective of this study is to evaluate the diagnostic value of commercial Western Blot (WB) method in the serological diagnosis of H. pylori infections against the H. pylori Ag in stool (HpSAg) using commercial enzyme-linked immunoassay (ELISA) in adult dyspeptic Egyptian patients. Also we investigated the prevalence of virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) in the infected patients. Samples from 46 adult dyspeptic Egyptian patients were tested by the two methods. WB test gave accurate confirmed result with (82.6% accuracy and 89.5% sensitivity) compared to HpSAg test. Also the results indicated a high seroprevalence of cagA- and vacA-positive virulent H. pylori type I strains in adult infected population indicate that such strains may be common in this population and responsible for the majority of H. pylori infection among adult Egyptians. We concluded that WB method could be useful for the confirmatory detection of antibody profiles to H. pylori antigens and virulence factors in adult Egyptian patients.Int J Appl Sci Biotechnol, Vol 4(3): 352-358


Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 338-343 ◽  
Author(s):  
S Maeda ◽  
K Ogura ◽  
H Yoshida ◽  
F Kanai ◽  
T Ikenoue ◽  
...  

Background—VacA and CagA proteins have been reported to be major virulence factors of Helicobacter pylori. However, antibodies against these proteins are frequently found in the sera of Japanese patients regardless of their gastroduodenal status.Aim—To evaluate the expression of VacA and CagA proteins by H pylori strains isolated in Japan.Methods—By using specific antibodies raised against recombinant VacA and CagA proteins, the expression of VacA and CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a vacuolating assay and genotyping of thevacA gene were also used in the evaluation. The results were analysed in relation to the gastroduodenal diseases of the hosts.Results—VacA and CagA proteins were expressed in 59/68 (87%) and in 61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68 (84%) isolates, indicating that most immunologically VacA positive strains produced active cytotoxin. The prevalence of infection with strains expressing CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%), irrespective of the gastroduodenal status of the host.Conclusion—Most H pylori isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these virulence factors cannot be used as markers to discern the risk of developing serious gastroduodenal pathologies in the hosts. However, the high prevalence of infection with strains positive for vacuolating cytotoxin and CagA may contribute to the characteristics of H pylori infection in Japan.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Jacek Baj ◽  
Alicja Forma ◽  
Monika Sitarz ◽  
Piero Portincasa ◽  
Gabriella Garruti ◽  
...  

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.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 331
Author(s):  
Montserrat Palau ◽  
Núria Piqué ◽  
M. José Ramírez-Lázaro ◽  
Sergio Lario ◽  
Xavier Calvet ◽  
...  

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.


2006 ◽  
Vol 74 (7) ◽  
pp. 4064-4074 ◽  
Author(s):  
Mónica Oleastro ◽  
Lurdes Monteiro ◽  
Philippe Lehours ◽  
Francis Mégraud ◽  
Armelle Ménard

ABSTRACT Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex- and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.


2020 ◽  
Vol 14 (1) ◽  
pp. 72-79
Author(s):  
Ahmed Husham Salman ◽  
Aumed Arshad Hawezy

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.


2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Vudumula Vijaya Lakshmi

Helicobacter pylori (H. pylori) has a role in the multifactorial etiology of peptic ulcer disease. A link between H. pylori infection and duodenal ulcer disease is now established. Other contributing factors and their interaction with the organism may initiate the ulcerative process. The fact that eradication of H. pylori infection leads to a long-term cure in the majority of duodenal ulcer patients and the fact that the prevalence of infection is higher in ulcer patients than in the normal population are cogent arguments in favor of it being the primary cause of the ulceration. This study was under taken at the Department of surgery, Narayana medical college, Nellore from January 2007 to July 2008. A total of 150 patients with duodenal ulcers, gastric ulcers, antral gastritis, gastric carcinoma and dyspepsia of any kind were studied. Maximum number of cases were in the age group of 31 years to 50 years among both sexes and number of cases gradually decreased after 50 years of age in males and females. Males were more in number and male to female ratio is (2.75:1) approximately 3:1.


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