Significance of dormant forms of Helicobacter pylori in ulcerogenesis.
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ABSTRACT:
SUBMITTER: Reshetnyak VI
PROVIDER: S-EPMC5526757 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Prophages of Helicobacter pylori, a bacterium known to co-evolve in the stomach of its human host, were recently identified. However, their role in the diversity of H. pylori strains is unknown. We demonstrate here and for the first time that the diversity of the prophage genes offers the ability to distinguish between European populations, and that H. pylori prophages and their host bacteria share a complex evolutionary history. By comparing the phylogenetic trees of two prophage genes (integrase and holin) and the multilocus sequence typing (MLST)-based data obtained for seven housekeeping genes, we observed that the majority of the strains belong to the same phylogeographic group in both trees. Furthermore, we found that the Bayesian analysis of the population structure of the prophage genes identified two H. pylori European populations, hpNEurope and hpSWEurope, while the MLST sequences identified one European population, hpEurope. The population structure analysis of H. pylori prophages was even more discriminative than the traditional MLST-based method for the European population. Prophages are new players to be considered not only to show the diversity of H. pylori strains but also to more sharply define human populations.
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Project description:Some strains of Helicobacter pylori are known to produce an extracellular cytotoxin that causes vacuolization in various mammalian cells. In this study, we found that concentrated culture supernatants from four Helicobacter strains isolated from patients infected with the bacterium, but having normal gastric mucosa, lacked cytotoxic activity. We also show that a higher percentage of strains isolated from patients with polymorphonuclear leukocyte infiltration of gastric mucosa are toxin positive (78%) versus those isolated from patients lacking such infiltration (33%). In addition to examining the relationship between pathology and cytotoxic activity, we used the previously published N-terminal sequence of the protein to clone and characterize vacA, the structural gene encoding the cytotoxin. Briefly, three oligonucleotides capable of encoding the first nine amino acids corresponding to the sense strand and four oligonucleotides corresponding to the noncoding strand of the last seven known amino acids of the cytotoxin protein were made. They were used in all 12 possible combinations in 12 different PCR reactions, with DNA from a cytotoxin-positive strain as template. In four combinations, the expected 69-bp fragment was seen. The sequence of this 69-bp fragment confirmed that it encoded the known N-terminal sequence of the cytotoxin. This gene is capable of encoding a 136-kDa protein with a 33-amino-acid signal peptide, whereas the purified cytotoxin is only 87 kDa, suggesting processing in the C-terminal region of the protein. A single copy of the vacA gene encodes the cytotoxin in H. pylori. Consequently, the insertion of a kanamycin resistance marker in the vacA gene produced an isogenic mutant lacking the cytotoxic activity. This mutant provides genetic evidence that vacA encodes the cytotoxin. Sequence analysis of the DNA adjacent to the vacA gene demonstrated that this gene is next to a putative cysteinyl tRNA synthetase gene. From the sequence arrangement, we predict that there are no other genes transcribed together with vacA. We also show that five of seven cytotoxin-negative strains examined still carry the sequences encoding it whereas the other two have suffered a deletion of the vacA gene. We further show that in at least one cytotoxin-negative but vacA-positive strain (MO19), there are variations in the length of the vacA gene that could explain the cytotoxin-negative phenotype in this strain.
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Project description:Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.
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Project description:Flagella-driven motility is essential for Helicobacter pylori to colonize the human stomach, where it causes a variety of diseases, including chronic gastritis, peptic ulcer disease, and gastric cancer. H. pylori has evolved a high-torque-generating flagellar motor that possesses several accessories not found in the archetypical Escherichia coli motor. FlgV was one of the first flagellar accessory proteins identified in Campylobacter jejuni, but its structure and function remain poorly understood. Here, we confirm that deletion of flgV in H. pylori B128 and a highly motile variant of H. pylori G27 (G27M) results in reduced motility in soft agar medium. Comparative analyses of in-situ flagellar motor structures of wild-type, ΔflgV, and a strain expressing FlgV-YFP showed that FlgV forms a ring-like structure closely associated with the junction of two highly conserved flagellar components: the MS and C rings. The results of our studies suggest that the FlgV ring has adapted specifically in Campylobacterota to support the assembly and efficient function of the high-torque-generating motors.
| S-EPMC10655999 | biostudies-literature
Project description:The primary mode of transmission of Helicobacter pylori, a human pathogen carried by more than half the population worldwide, is still unresolved. Some epidemiological data suggest water as a possible transmission route. H. pylori in the environment transforms into a nonculturable, coccoid form, which frequently results in the failure to detect this bacterium in environmental samples by conventional culture techniques. To overcome limitations associated with culturing, molecular approaches based on DNA amplification by PCR have been developed and used for the detection of H. pylori in clinical and environmental samples. Our results showed the glmM gene as the most promising target for detection of H. pylori by PCR amplification. Under optimal amplification conditions, glmM-specific primers generated PCR-amplified products that were specific for H. pylori and some other Helicobacter species. Genome sequence analysis revealed the existence of a conserved region linked to a hypervariable region upstream of the 16S rRNA gene of H. pylori. Selective PCR primer sets targeting this sequence were evaluated for the specific detection of H. pylori. One primer set, Cluster2 and B1J99, were shown to be highly specific for H. pylori strains and did not produce any PCR products when other Helicobacter species and other bacterial species were analyzed. In tests with 32 strains of H. pylori, 6 strains of other Helicobacter species, 8 strains of Campylobacter jejuni, and 21 strains belonging to different genera, the primers for glmM were selective for the Helicobacter genus and the primers containing the region flanking the 16S rRNA gene were selective for H. pylori species only. The combination of two sensitive PCR-based methods, one targeting the glmM gene and the other targeting a hypervariable flanking region upstream of the 16S rRNA gene, are complementary to each other. Whereas the glmM-specific primers provide a rapid, sensitive presumptive assay for the presence of H. pylori and closely related Helicobacter spp., the primers for sequences flanking the 16S rRNA gene can confirm the presence of H. pylori and locate the potential source of this bacterium.
| S-EPMC497564 | biostudies-literature
Project description:Helicobacter pylori is a common bacterial infection. It can lead to severe stomach problems, including stomach cancer. Researchers want to look at samples of the bacteria. These H. pylori strains will be taken from chronically infected people. They want to identify the genetic and epigenetic differences in H. pylori strains. This could help predict which people who get infected with the bacteria will get stomach cancer. This could lead to the cancer being detected earlier. It could also mean less people get stomach cancer.
Objectives:
To study genetic variations of H. pylori strains based on samples from chronically infected people. To identify the features of strains that might lead to severe stomach problems or stomach cancer.
Eligibility:
People ages 30-70 years who need an upper endoscopy or who were recently diagnosed with stomach cancer
Design:
Participants will be screened by the doctor who does their procedure and a study nurse.
Participants who have endoscopy will have ~6 biopsies removed. These are tissue samples. They are about the size of a grain of rice. Participants will allow the study team to access reports from their stomach exam.
Participants with stomach cancer will donate some of the tissue that will be removed during their clinical care. They will allow the study team to access reports of their surgery. They will also allow them to access the microscope slides of their stomach.
| 2216372 | ecrin-mdr-crc
Project description:Sexual reproduction and recombination are essential for the survival of most eukaryotic populations. Until recently, the impact of these processes on the structure of bacterial populations has been largely overlooked. The advent of large-scale whole-genome sequencing and the concomitant development of molecular tools, such as microarray technology, facilitate the sensitive detection of recombination events in bacteria. These techniques are revealing that bacterial populations are comprised of isolates that show a surprisingly wide spectrum of genetic diversity at the DNA level. Our new awareness of this genetic diversity is increasing our understanding of population structures and of how these affect host?pathogen relationships. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2005-10-20 | GSE3479 | GEO
Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study，the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined.
2012-04-30 | GSE30042 | GEO
Project description:The Helicobacter pylori iceA gene was recently identified as a genetic marker for the development of peptic ulcer in a Western population. To assess the significance of iceA subtypes of H. pylori in relation to peptic ulcer, 140 Japanese clinical isolates (88 from Fukui and 52 from Okinawa) were characterized. Sequence analysis of the iceA1 gene from 25 representative Japanese strains was also carried out to identify the differences in iceA between the ulcer group and the gastritis group. The iceA1 genotype was not correlated with the presence of peptic ulceration in either area. In addition, sequence analysis led to identification of five deletions and five point mutations (a nonsense mutation or a 1-bp insertion) within the iceA1 open reading frame corresponding to previously published sequences. These mutations were identified in both clinical groups (ulcer and gastritis groups) in each area. Local DNA sequence analysis revealed that the endpoints of all five deletions coincided with direct repeats. We also found four strains that carried longer iceA1 open reading frames compared with that for strain 60190. In conclusion, carriage of an iceA1 strain does not seem to be a risk factor for peptic ulcer in Japanese subjects. The critical mutations in the iceA1 gene in some isolates from patients with peptic ulcers suggested that IceA does not participate in the pathogenesis of peptic ulcer in Japan. We also found deletion hot spots that were associated with direct repeats in iceA1 and that favored a small-deletion model of slipped mispairing events during replication. We showed that iceA1 sequence variations may be useful tools for analysis of the population genetics of H. pylori.
| S-EPMC86129 | biostudies-literature
Project description:The variability of Helicobacter pylori morphology and the heterogeneity of virulence factors expressed by these bacteria play a key role as a driving force for adaptation to the hostile stomach environment. The aim of the study was to determine the relationship between the presence of certain genes encoding virulence factors and H. pylori morphology. One reference and 13 clinical H. pylori strains with a known virulence profile (vacA, cagA, babA2, dupA, and iceA) were used in this study. Bacteria were cultured for 1 h and 24 h in stressogenic culture conditions, i.e., serum-free BHI broths at suboptimal conditions (room temperature and atmosphere, without shaking). H. pylori cell morphology was observed by light and scanning electron microscopy. The vacA polymorphism and the cagA and babA2 presence were positively correlated with the reduction in cell size. Exposure to short-time stressogenic conditions caused more intense transformation to coccoid forms in highly pathogenic H. pylori type I strains (35.83% and 47.5% for type I s1m2 and I s1m1, respectively) than in intermediate-pathogenic type III (8.17%) and low pathogenic type II (9.92%) strains. The inverse relationship was observed for the number of rods, which were more common in type III (46.83%) and II (48.42%) strains than in type I s1m2 (19.25%) or I s1m1 (6.58%) strains. Our results suggest that there is a close relationship between the presence of virulence genes of H. pylori strains and their adaptive morphological features.
| S-EPMC6529389 | biostudies-literature