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

mBio ◽  
2010 ◽  
Vol 1 (3) ◽  
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.

scholarly journals Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution

2021 ◽  
Vol 9 (2) ◽  
pp. 240
Author(s):  
Bruno Cavadas ◽  
Marina Leite ◽  
Nicole Pedro ◽  
Ana C. Magalhães ◽  
Joana Melo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Host Response ◽  
Homo Sapiens ◽  
European Ancestry ◽  
Genome Wide ◽  
Expression Host ◽  
H Pylori ◽  
Human Ancestry

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

scholarly journals Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huan Wang ◽  
Nian-Shuang Li ◽  
Cong He ◽  
Chuan Xie ◽  
Yin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Gene Expression Data ◽  
Functional Enrichment ◽  
Expression Data ◽  
H Pylori

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples ( P < 0.05 ). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

scholarly journals In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 20
Author(s):  
Maciej Spiegel ◽  
Paweł Krzyżek ◽  
Ewa Dworniczek ◽  
Ryszard Adamski ◽  
Zbigniew Sroka
Keyword(s):  
Helicobacter Pylori ◽  
In Silico ◽  
Stringent Response ◽  
Human Pathogens ◽  
Gastric Diseases ◽  
Natural Substances ◽  
Interesting Candidate ◽  
H Pylori ◽  
Static Conditions

Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.

scholarly journals Expression of Helicobacter pylori Virulence Factors and Associated Expression Profiles of Inflammatory Genes in the Human Gastric Mucosa

2007 ◽  
Vol 75 (11) ◽  
pp. 5118-5126 ◽  
Author(s):  
Sicheng Wen ◽  
Dominique Velin ◽  
Christian P. Felley ◽  
Likun Du ◽  
Pierre Michetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Expression Patterns ◽  
Human Gastric Mucosa ◽  
H Pylori

ABSTRACT Helicobacter pylori virulence factors have been suggested to be important in determining the outcome of infection. The H. pylori adhesion protein BabA2 is thought to play a crucial role in bacterial colonization and in induction of severe gastric inflammation, particularly in combination with expression of CagA and VacA. However, the influence of these virulence factors on the pathogenesis of H. pylori infection is still poorly understood. To address this question, the inflammatory gene expression profiles for two groups of patients infected with triple-negative strains (lacking expression of cagA, babA2, and vacAs1 but expressing vacAs2) and triple-positive strains (expressing cagA, vacAs1, and babA2 but lacking expression of vacAs2) were investigated. The gene expression patterns in the antrum gastric mucosa from patients infected with different H. pylori strains were very similar, and no differentially expressed genes could be identified by pairwise comparisons. Our data thus suggest that there is a lack of correlation between the host inflammatory responses in the gastric mucosa and expression of the babA2, cagA, and vacAs1 genes.

scholarly journals Helicobacter pylori Stimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4+ T Lymphocytes

2009 ◽  
Vol 78 (2) ◽  
pp. 845-853 ◽  
Author(s):  
Wafa Khamri ◽  
Marjorie M. Walker ◽  
Peter Clark ◽  
John C. Atherton ◽  
Mark R. Thursz ◽  
...  
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
Dendritic Cells ◽  
Virulence Factors ◽  
Human Monocyte ◽  
Interleukin 17 ◽  
Th17 Response ◽  
H Pylori

ABSTRACT Helicobacter pylori is a human gastroduodenal pathogen that leads to active chronic inflammation characterized by T-cell responses biased toward a Th1 phenotype. It has been accepted that H. pylori infection induces a Th17 response. At mucosal sites, dendritic cells (DCs) have the capacity to induce effector T cells. Here, we evaluate the role of DCs in the H. pylori-induced interleukin-17 (IL-17) response. Immunohistochemistry and immunofluorescence were performed on human gastric mucosal biopsy samples and showed that myeloid DCs in H. pylori-infected patients colocalized with IL-23- and that IL-17-producing lymphocytes were present in H. pylori-infected antral biopsy samples. In parallel, human monocyte-derived DCs stimulated in vitro with live H. pylori cells produced significant levels of IL-23 in the absence of IL-12 release. The subsequent incubation of H. pylori-infected DCs with autologous CD4+ T cells led to gamma interferon (IFN-γ) and IL-17 expression. The inhibition of IL-1 and, to a lesser extent, IL-23 inhibited IL-17 production by T cells. Finally, isogenic H. pylori mutant strains not expressing major virulence factors were less effective in inducing IL-1 and IL-23 release by DCs and IL-17 release by T cells than parental strains. Altogether, we can conclude that DCs are potent inducers of IL-23/IL-17 expression following H. pylori stimulation. IL-1/IL-23 as well as H. pylori virulence factors seem to play an important role in mediating this response.

scholarly journals Metal homeostasis in pathogenic Epsilonproteobacteria: Mechanisms of acquisition and regulation

Metallomics ◽  
2020 ◽  
Author(s):  
Brittni R Kelley ◽  
Jacky Lu ◽  
Kathryn P Haley ◽  
Jennifer A Gaddy ◽  
Jeremiah G Johnson
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Campylobacter Jejuni ◽  
Bacterial Virulence ◽  
Metal Availability ◽  
Human Pathogens ◽  
Disease Outcomes ◽  
Animal Hosts ◽  
H Pylori ◽  
Reducing Bacteria

Abstract Epsilonproteobacteria are a diverse class of eubacteria within the Proteobacteria phylum that includes environmental sulfur-reducing bacteria and the human pathogens, Campylobacter jejuni and Helicobacter pylori. These pathogens infect and proliferate within the gastrointestinal tracts of multiple animal hosts, including humans, and cause a variety of disease outcomes. While infection of these hosts provides nutrients for the pathogenic Epsilonproteobacteria, many hosts have evolved a variety of strategies to either sequester metals from the invading pathogen or exploit the toxicity of metals and drive their accumulation as an antimicrobial strategy. As a result, C. jejuni and H. pylori have developed mechanisms to sense changes in metal availability and regulate their physiology in order to respond to either metal limitation or accumulation. In this review, we will discuss the challenges of metal availability at the host-pathogen interface during infection with C. jejuni and H. pylori and describe what is currently known about how these organisms alter their gene expression and/or deploy bacterial virulence factors in response to these environments.

The rod-to-coccoid body transformation in cultures of Helicobacter pylori

1990 ◽  
Vol 48 (3) ◽  
pp. 626-627
Author(s):  
A. R. Crooker ◽  
W. G. Kraft ◽  
T. L. Beard ◽  
M. C. Myers
Keyword(s):  
Helicobacter Pylori ◽  
Growth Cycle ◽  
Negative Bacterium ◽  
Body Formation ◽  
Coccoid Form ◽  
Spiral Form ◽  
Prolonged Culture ◽  
H Pylori ◽  
Upper Gastrointestinal

Helicobacter pylori is a microaerophilic, gram-negative bacterium found in the upper gastrointestinal tract of humans. There is strong evidence that H. pylori is important in the etiology of gastritis; the bacterium may also be a major predisposing cause of peptic ulceration. On the gastric mucosa, the organism exists as a spiral form with one to seven sheathed flagella at one (usually) or both poles. Short spirals were seen in the first successful culture of the organism in 1983. In 1984, Marshall and Warren reported a coccoid form in older cultures. Since that time, other workers have observed rod and coccal forms in vitro; coccoid forms predominate in cultures 3-7 days old. We sought to examine the growth cycle of H. pylori in prolonged culture and the mode of coccoid body formation.

Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors

2019 ◽  
Vol 19 (5) ◽  
pp. 376-382 ◽  
Author(s):  
Sachin Jangra ◽  
Gayathri Purushothaman ◽  
Kapil Juvale ◽  
Srimadhavi Ravi ◽  
Aishwarya Menon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Infections ◽  
Immunosuppressive Drugs ◽  
Multi Drug Resistance ◽  
Metabolic Enzyme ◽  
World Population ◽  
Inhibitor Molecule ◽  
Nucleotide Synthesis ◽  
H Pylori

Background & Objective:Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5′-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively.Methods:In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH.Results:In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively.Conclusion:When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.

Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

2019 ◽  
Vol 16 (4) ◽  
pp. 392-400 ◽  
Author(s):  
Göknil Pelin Coşkun ◽  
Teodora Djikic ◽  
Sadık Kalaycı ◽  
Kemal Yelekçi ◽  
Fikrettin Şahin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Enzyme Inhibitors ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Urease Enzyme ◽  
H Pylori ◽  
Ulcer Treatment ◽  
Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today&#039;s standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2&#039;,4&#039;-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2&#039;,4&#039;-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2&#181;g/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

scholarly journals Nutrient Deficiency Promotes the Entry of Helicobacter pylori Cells into Candida Yeast Cells

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 426
Author(s):  
Kimberly Sánchez-Alonzo ◽  
Fabiola Silva-Mieres ◽  
Luciano Arellano-Arriagada ◽  
Cristian Parra-Sepúlveda ◽  
Humberto Bernasconi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Nutrient Deficiency ◽  
Gastric Epithelium ◽  
Yeast Cells ◽  
Nutrient Concentrations ◽  
Fetal Bovine ◽  
H Pylori ◽  
Pcr Techniques ◽  
Strain Dependent

Helicobacter pylori, a Gram-negative bacterium, has as a natural niche the human gastric epithelium. This pathogen has been reported to enter into Candida yeast cells; however, factors triggering this endosymbiotic relationship remain unknown. The aim of this work was to evaluate in vitro if variations in nutrient concentration in the cultured medium trigger the internalization of H. pylori within Candida cells. We used H. pylori–Candida co-cultures in Brucella broth supplemented with 1%, 5% or 20% fetal bovine serum or in saline solution. Intra-yeast bacteria-like bodies (BLBs) were observed using optical microscopy, while intra-yeast BLBs were identified as H. pylori using FISH and PCR techniques. Intra-yeast H. pylori (BLBs) viability was confirmed using the LIVE/DEAD BacLight Bacterial Viability kit. Intra-yeast H. pylori was present in all combinations of bacteria–yeast strains co-cultured. However, the percentages of yeast cells harboring bacteria (Y-BLBs) varied according to nutrient concentrations and also were strain-dependent. In conclusion, reduced nutrients stresses H. pylori, promoting its entry into Candida cells. The starvation of both H. pylori and Candida strains reduced the percentages of Y-BLBs, suggesting that starving yeast cells may be less capable of harboring stressed H. pylori cells. Moreover, the endosymbiotic relationship between H. pylori and Candida is dependent on the strains co-cultured.

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