scholarly journals Protective effects of Helicobacter pylori membrane vesicles against stress and antimicrobial agents

Microbiology ◽  
2020 ◽  
Vol 166 (8) ◽  
pp. 751-758 ◽  
Author(s):  
Benjamin Oliver Murray ◽  
Robin Andrew Dawson ◽  
Lolwah Mohammad Alsharaf ◽  
Jody Anne Winter
Keyword(s):  
Helicobacter Pylori ◽  
Type Species ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Content Type ◽  
Link Type ◽  
H Pylori

Outer-membrane vesicles (OMVs) produced by Helicobacter pylori deliver bacterial components to host cells, provide a mechanism for stabilization of secreted components and may allow the bacteria to exert ‘long-range’ effects in the gastric niche, promoting persistence. In addition to their well-characterized host cell interactions, membrane vesicles improve stress survival in other bacterial species, and are constitutively produced by both pathogenic and non-pathogenic bacteria. We aimed to determine whether OMVs could improve H. pylori survival of a range of stressors. The effects of purified OMVs on the resistance of H. pylori to a range of environmental and antimicrobial stresses were determined using growth curves and survival assays. Addition of purified OMVs to H. pylori cultures provided dose-dependent protection against hydrogen peroxide-mediated killing. Supplementation with OMVs also partially protected H. pylori against the bactericidal effects of the antibiotics clarithromycin and levofloxacin, but not against amoxicillin nor metronidazole. Addition of purified OMVs allowed H. pylori to grow in the presence of inhibitory concentrations of the antimicrobial peptide LL-37. In the presence of 50 µg OMVs ml−1, significantly enhanced H. pylori growth was observed at higher LL-37 concentrations compared with lower LL-37 concentrations, suggesting that OMV–LL-37 interactions might facilitate release of growth-promoting nutrients. Taken together, these data indicate that production of membrane vesicles could help H. pylori to survive exposure to antibiotics and host antimicrobial defences during infection.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Carbonic Anhydrases: New Perspectives on Protein Functional Role and Inhibition in Helicobacter pylori

2021 ◽  
Vol 12 ◽  
Author(s):  
Cristina Campestre ◽  
Viviana De Luca ◽  
Simone Carradori ◽  
Rossella Grande ◽  
Vincenzo Carginale ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Pathogenic Bacteria ◽  
Acid Tolerance ◽  
Membrane Vesicles ◽  
Research Field ◽  
Outer Membrane Vesicles ◽  
Bacterial Toxin ◽  
Carbonic Anhydrases ◽  
Ph Homeostasis ◽  
H Pylori

Our understanding of the function of bacterial carbonic anhydrases (CAs, EC 4.2.1.1) has increased significantly in the last years. CAs are metalloenzymes able to modulate CO2, HCO3– and H+ concentration through their crucial role in catalysis of reversible CO2 hydration (CO2 + H2O ⇄ HCO3– + H+). In all living organisms, CA activity is linked to physiological processes, such as those related to the transport and supply of CO2 or HCO3–, pH homeostasis, secretion of electrolytes, biosynthetic processes and photosynthesis. These important processes cannot be ensured by the very low rate of the non-catalyzed reaction of CO2 hydration. It has been recently shown that CAs are important biomolecules for many bacteria involved in human infections, such as Vibrio cholerae, Brucella suis, Salmonella enterica, Pseudomonas aeruginosa, and Helicobacter pylori. In these species, CA activity promotes microorganism growth and adaptation in the host, or modulates bacterial toxin production and virulence. In this review, recent literature in this research field and some of the above-mentioned issues are discussed, namely: (i) the implication of CAs from bacterial pathogens in determining the microorganism growth and virulence; (ii) the druggability of these enzymes using classical CA inhibitors (CAIs) of the sulfonamide-type as examples; (iii) the role played by Helicobacter pylori CAs in the acid tolerance/adaptation of the microbe within the human abdomen; (iv) the role of CAs played in the outer membrane vesicles spawned by H. pylori in its planktonic and biofilm phenotypes; (v) the possibility of using H. pylori CAIs in combination with probiotic strains as a novel anti-ulcer treatment approach. The latter approach may represent an innovative and successful strategy to fight gastric infections in the era of increasing resistance of pathogenic bacteria to classical antibiotics.

scholarly journals Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Vo Phuoc Tuan ◽  
Koji Yahara ◽  
Ho Dang Quy Dung ◽  
Tran Thanh Binh ◽  
Pham Huu Tung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Type Species ◽  
Genetic Variations ◽  
Genome Wide Association ◽  
Content Type ◽  
Link Type ◽  
Genome Wide ◽  
H Pylori

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.

scholarly journals Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

2020 ◽  
Vol 8 (9) ◽  
pp. 1328 ◽  
Author(s):  
Miroslaw Jarzab ◽  
Gernot Posselt ◽  
Nicole Meisner-Kober ◽  
Silja Wessler
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Current Knowledge ◽  
Membrane Vesicles ◽  
Bacterial Pathogenesis ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
H Pylori

Persistent infections with the human pathogen Helicobacter pylori (H. pylori) have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of H. pylori is determined by a complicated network of manifold mechanisms of pathogen–host interactions, which involves a coordinated interplay of H. pylori pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from H. pylori and their implication in bacterial pathogenesis is not well developed. In this review, we summarize the current knowledge on H. pylori-derived OMVs.

scholarly journals Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR–IκB Kinase–NF-κB Pathways in Dendritic Cells

2016 ◽  
Vol 84 (8) ◽  
pp. 2162-2174 ◽  
Author(s):  
Su Hyuk Ko ◽  
Da Jeong Rho ◽  
Jong Ik Jeon ◽  
Young-Jeon Kim ◽  
Hyun Ae Woo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Dendritic Cells ◽  
Outer Membrane ◽  
Heme Oxygenase ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Heme Oxygenase 1 ◽  
Content Type ◽  
Iκb Kinase ◽  
H Pylori

Helicobacter pylorisheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses againstH. pylori, and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. AlthoughH. pylori-derived OMVs may contribute to the pathogenesis ofH. pyloriinfection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role ofH. pylori-derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crudeH. pyloriOMVs upregulated HO-1 expression. Crude OMVs obtained from acagA-negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. CrudeH. pyloriOMVs activated signals of transcription factors such as NF-κB, AP-1, and Nrf2. Suppression of NF-κB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV-induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IκB kinase (IKK), NF-κB, and HO-1 expression in crude OMV-exposed DCs. These results suggest thatH. pylori-derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR–IKK–NF-κB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses inH. pyloriinfection.

scholarly journals Evaluation of protective immunity responses against pneumococcal PhtD and its C-terminal in combination with outer-membrane vesicles as adjuvants

2020 ◽  
Vol 69 (3) ◽  
pp. 465-477
Author(s):  
Mohammadali Malekan ◽  
Seyed Davar Siadat ◽  
Mohammadreza Aghasadeghi ◽  
Nader Shahrokhi ◽  
Parviz Afrough ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Type Species ◽  
Survival Rates ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Content Type ◽  
Link Type ◽  
Bactericidal Assay ◽  
Serum Bactericidal Assay ◽  
Specific Igg

Introduction. Streptococcus pneumoniae is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application. Aim. Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate. Methodology. We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant. Results. The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of S. pneumoniae ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge. Conclusion. The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.

scholarly journals Blue light emitting diodes enhance the antivirulence effects of Curcumin against Helicobacter pylori

2020 ◽  
Vol 69 (4) ◽  
pp. 617-624 ◽  
Author(s):  
Homa Darmani ◽  
Ehda A.M. Smadi ◽  
Sereen M.B. Bataineh
Keyword(s):  
Helicobacter Pylori ◽  
Blue Light ◽  
Type Species ◽  
Light Emitting Diodes ◽  
Light Therapy ◽  
Content Type ◽  
Light Emitting ◽  
Link Type ◽  
Urease Production ◽  
H Pylori

Introduction. Growing concern about the increasing frequency of resistance of Helicobacter pylori to the available antimicrobial agents worldwide has encouraged the search for new strategies in treating and eradicating H. pylori infections. Endoscopic blue-light therapy has been used in patients with H. pylori gastritis with limited success due to subsequent repopulation with H. pylori . Clinical trials using Curcumin could not eradicate infection either. Aim. We studied the effect of blue light emitting diodes (LEDs) in conjunction with Curcumin on H. pylori , since this has not been previously reported. Methodology. We examined the effect of Curcumin with and without irradiation with blue LEDs on the viability of H. pylori and four key factors important for colonization and establishment of H. pylori infection, namely urease production, motility, adhesion and biofilm formation. Results. We found that a combination of Curcumin and blue LEDs caused significant reductions in viability, urease production, motility, haemagglutination activity, as well as increased disruption of mature preformed biofilms of H. pylori , in comparison to Curcumin alone (P<0.0001), at sublethal concentrations of Curcumin. Conclusion. Targeting the virulence factors of H. pylori with blue LED photoactivated Curcumin would theoretically cripple this pathogen from colonizing and causing tissue damage and perhaps overcome the problem of repopulation with H. pylori that often occurs following endoscopic blue-light therapy.

scholarly journals hfqPlays Important Roles in Virulence and Stress Adaptation in Cronobacter sakazakii ATCC 29544

2015 ◽  
Vol 83 (5) ◽  
pp. 2089-2098 ◽  
Author(s):  
Seongok Kim ◽  
Hyelyeon Hwang ◽  
Kwang-Pyo Kim ◽  
Hyunjin Yoon ◽  
Dong-Hyun Kang ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Soft Agar ◽  
Host Cells ◽  
Neonatal Meningitis ◽  
Animal Cells ◽  
Content Type ◽  
Flagellar Biosynthesis

Cronobacterspp. are opportunistic pathogens that cause neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated withCronobacterinfection, the mechanisms of pathogenesis are still being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq inC. sakazakiivirulence. In the absence ofhfq,C. sakazakiiwas highly attenuated in disseminationin vivo, showed defects in invasion (3-fold) into animal cells and survival (103-fold) within host cells, and exhibited low resistance to hydrogen peroxide (102-fold). Remarkably, the loss ofhfqled to hypermotility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyperflagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagellar biosynthesis in a strain lackinghfq. Together, these data strongly suggest thathfqplays important roles in the virulence ofC. sakazakiiby participating in the regulation of multiple genes.

scholarly journals d-Serine induces distinct transcriptomes in diverse Escherichia coli pathotypes

Microbiology ◽  
2021 ◽  
Vol 167 (10) ◽  
Author(s):  
James P. R. Connolly ◽  
Natasha C. A. Turner ◽  
Jennifer C. Hallam ◽  
Patricia T. Rimbi ◽  
Tom Flett ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Type Species ◽  
Pathogenic Bacteria ◽  
Neonatal Meningitis ◽  
Published Data ◽  
Toxic Metabolite ◽  
Transcriptional Responses ◽  
Content Type ◽  
E Coli ◽  
Link Type

Appropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood. d-Serine (d-ser) is a toxic metabolite present in highly variable concentrations at different colonization sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of three Escherichia coli pathotypes – enterohaemorrhagic E. coli (EHEC), uropathogenic E. coli (UPEC) and neonatal meningitis-associated E. coli (NMEC) – to d-ser was highly distinct. In fact, we identified no single differentially expressed gene common to all three strains. We observed the induction of ribosome-associated genes in extraintestinal pathogens UPEC and NMEC only, and the induction of purine metabolism genes in gut-restricted EHEC, and UPEC indicating distinct transcriptional responses to a common signal. UPEC and NMEC encode dsdCXA – a genetic locus required for detoxification and hence normal growth in the presence of d-ser. Specific transcriptional responses were induced in strains accumulating d-ser (WT EHEC and UPEC/NMEC mutants lacking the d-ser-responsive transcriptional activator DsdC), corroborating the notion that d-ser is an unfavourable metabolite if not metabolized. Importantly, many of the UPEC-associated transcriptome alterations correlate with published data on the urinary transcriptome, supporting the hypothesis that d-ser sensing forms a key part of urinary niche adaptation in this pathotype. Collectively, our results demonstrate distinct pleiotropic responses to a common metabolite in diverse E. coli pathotypes, with important implications for niche selectivity.

scholarly journals The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α5β1 Integrin

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
William E. Sause ◽  
Daniela Keilberg ◽  
Soufiane Aboulhouda ◽  
Karen M. Ottemann
Keyword(s):  
Helicobacter Pylori ◽  
Host Cell ◽  
Type Iv Secretion ◽  
Host Cells ◽  
Wild Type ◽  
Content Type ◽  
Type Iv ◽  
H Pylori ◽  
Α5β1 Integrin ◽  
Cell Interface

ABSTRACT The human pathogen Helicobacter pylori uses the host receptor α5β1 integrin to trigger inflammation in host cells via its cag pathogenicity island (cag PAI) type IV secretion system (T4SS). Here, we report that the H. pylori ImaA protein (HP0289) decreases the action of the cag PAI T4SS via tempering the bacterium's interaction with α5β1 integrin. Previously, imaA-null mutants were found to induce an elevated inflammatory response that was dependent on the cag PAI T4SS; here we extend those findings to show that the elevated response is independent of the CagA effector protein. To understand how ImaA could be affecting cag PAI T4SS activity at the host cell interface, we utilized the Phyre structural threading program and found that ImaA has a region with remote homology to bacterial integrin-binding proteins. This region was required for ImaA function. Unexpectedly, we observed that imaA mutants bound higher levels of α5β1 integrin than wild-type H. pylori, an outcome that required the predicted integrin-binding homology region of ImaA. Lastly, we report that ImaA directly affected the amount of host cell β1 integrin but not other cellular integrins. Our results thus suggest a model in which H. pylori employs ImaA to regulate interactions between integrin and the T4SS and thus alter the host inflammatory strength.

Sign in / Sign up

Export Citation Format

Share Document