Essential role of Helicobacter pylori apolipoprotein N-acyltransferase (Lnt) in stomach colonization
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1010783 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25799663_1.fastq.gz | Fastqsanger.gz | |||
| SRR25799663_2.fastq.gz | Fastqsanger.gz | |||
| SRR25799664_1.fastq.gz | Fastqsanger.gz | |||
| SRR25799664_2.fastq.gz | Fastqsanger.gz | |||
| SRR25799665_1.fastq.gz | Fastqsanger.gz |
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Project description:Deleting lnt changes the number of acyl chains on lipoproteins and the number of acyl chains on lipoproteins impacts the innate immune response through TLR2 signaling. We treated primary human gastric epithelial cells with a purified lipoprotein from wild-type or lnt mutant H. pylori and performed RNAseq. Differential gene expression analysis indicated lipoprotein from the lnt mutant induced a more robust TLR2 response.
2023-10-17 | GSE241938 | GEO
Project description:Chronic infection of the human stomach with Helicobacter pylori leads to a variety of pathologic sequelae including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection including the vacuolating cytotoxin and the cag pathogenicity island. Other factors important for establishment and maintenance of infection include urease enzyme production, motility, iron uptake and stress response. We utilized a C57BL/6 mouse infection model to query a collection of 2400 transposon mutants in two different bacterial strain backgrounds for H. pylori genetic loci contributing to colonization of the stomach. Microarray based tracking of transposon mutants allowed us to monitor the behavior of transposon insertions in 758 different gene loci. Of the loci measured 223 (29%) had a predicted colonization defect. These include previously described H. pylori virulence genes, genes implicated in virulence in other pathogenic bacteria and 81 hypothetical proteins. We have retested 10 previously uncharacterized candidate colonization gene loci by making independent null alleles and confirmed their colonization phenotype using competition experiments and determination of the dose required for 50% infection. Of the genetic loci retested, 60% have strain specific colonization defects while 40% had phenotypes in both strain backgrounds for infection, highlighting the profound effect of H. pylori strain variation on the pathogenic potential of this organism. This SuperSeries is composed of the SubSeries listed below.
2006-12-15 | GSE6531 | GEO
Project description:Bacterial-modulated gastric epithelial cells (GECs) play key roles in H. pylori-associated pathology. Here we demonstrate a pro-colonization and pro-inflammation role of GEC-expressed glycerol-3-phosphate acyltransferase 3 (GPAT3), a lipid metabolism-associated protein, in H. pylori infection. GPAT3 expression was elevated in gastric mucosa of both patients and mice infected with H. pylori. GPAT3 in GECs was synergistically induced by H. pylori and IL-22 in a cagA-dependent manner. Human gastric GPAT3 correlated with H. pylori colonization and the severity of gastritis, and mouse GPAT3 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il22-/-, Gpat3-/- and Il22-/-Gpat3-/- mice. Mechanistically, GPAT3 directly interacted with CCAR1 and activated IKKγ, subsequently promoted NF-κB phosphorylation whereby NF-kB directly bound to the promoters of MMP1, CXCL11 and IL-33 to activate their transcription, which not only led to decreased E-cadherin and zonula occludens-1 proteins by MMP1, thereby resulting in gastric mucosal damage and increased H. pylori colonization; but also resulted in increased gastric influx of CD8+ T cells via CXCL11-dependent migration and their subsequent IL-33-dependent IFN-γ production, thereby promoting H. pylori-associated gastritis. Overall, we propose a model in which GPAT3 collectively ensures H. pylori persistence and promotes gastritis.
2024-04-26 | GSE264450 | GEO
Project description:Bacterial lipoproteins are post-translationally modified with acyl chains, anchoring these proteins to bacterial membranes. In Gram-negative bacteria, three enzymes complete the modifications. Lgt (which adds two acyl chains) and LspA (which removes the signal peptide) are essential. Lnt (which adds a third acyl chain) is not essential in certain bacteria including Francisella tularensis, Neisseria gonorrhoeae, and Acinetobacter baumannii. Deleting lnt results in mild to severe physiologic changes. We previously showed lnt is not essential for Helicobacter pylori growth in vitro. Here, the physiologic consequences of deleting lnt in H. pylori and the role of Lnt in the host response to H. pylori were examined using in vitro and in vivo models. Comparing wild-type, Δlnt, and complemented mutant H. pylori, no changes in growth rates or sensitivity to acid or antibiotics were observed. Since deleting lnt changes the number of acyl chains on lipoproteins and the number of acyl chains on lipoproteins impacts the innate immune response through Toll-like receptor 2 (TLR2) signaling, primary human gastric epithelial cells were treated with a purified lipoprotein from wild-type or lnt mutant H. pylori. Differential gene expression analysis indicated that lipoprotein from the lnt mutant induced a more robust TLR2 response. In a complementary approach, we infected wild-type and Tlr2-/- mice and found that both the wild-type and complemented mutant strains successfully colonized the animals. However, the lnt mutant strain was unable to colonize either mouse strain. These results show that lnt is essential for H. pylori colonization and identifies lipoprotein synthesis as a target for therapeutic intervention.
| S-EPMC10715074 | biostudies-literature
Project description:Helicobacter pylori γ-glutamyltransferase (gGT) is a conserved virulence factor promoting bacterial colonization and immune tolerance. Although some studies addressed potential mechanisms explaining its function, the supportive role of gGT for in-vivo colonization remains unclear. In addition, it is unknown how differences in gGT expression observed for different strains may lead to compensatory mechanisms to ensure infection and persistence. Hence, it is of high importance to understand more profoundly the in-vivo function of this enzyme. In this study, we assessed acid survival under physiologic conditions mimicking the human gastric fluid and elevated the pH in the murine stomach prior to H. pylori infection to link gGT-mediated acid resistance to colonization. Furthermore, by comparing protein expression levels between wildtype and gGT-deficient H. pylori isolates before and after infecting mice, we systematically investigated proteomic adaptations of gGT-deficient bacteria during infection. Our data indicate that gGT plays a crucial role in sustaining urease activity in acidic environments, thereby supporting bacterial survival and successful colonization. The absence of gGT triggers the expression of proteins involved in nitrogen and iron metabolism, indicating a potential functional role of gGT in these metabolic pathways. Moreover, we observed an impaired growth of gGT-deficient strains in iron-restricted medium. In addition, the absence of gGT during infection leads to a significant overexpression of H. pylori adhesins and flagellar proteins, resulting in increased motility and adhesion capacity. In summary, we identified gGT-dependent mechanisms conferring a growth advantage to the bacterium in the gastric environment, which renders gGT a valuable target for the development of new treatments against H. pylori infection.
2025-04-08 | PXD050334 | Pride
Project description:Bacterial-modulated gastric epithelial cells (GECs) play key roles in H. pylori-associated pathology. Here we demonstrate both pro-colonization and pro-inflammation roles of GEC-derived PPFIA4, originally expressed in nervous system, in H. pylori infection. PPFIA4 was elevated in gastric mucosa of H. pylori-infected patients and mice. PPFIA4 in GECs was synergistically induced by H. pylori and IL-33 in a cagA-dependent manner. Human gastric PPFIA4 correlated with H. pylori colonization and the severity of gastritis, and H. pylori colonization and inflammation were attenuated in Ppfia4-/- and Ppfia4ΔGEC mice.Overall, we propose a model in which PPFIA4 collectively ensures H. pylori persistence and promotes gastritis.
2025-11-11 | GSE272270 | GEO
Project description:Helicobacter pylori (H. pylori) infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology is unknown. Here we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a-/-, Angptl4-/-, Il17a-/-Angptl4-/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation through binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.
2024-05-15 | GSE266891 | GEO
Project description:Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation. Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway. Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities. Gastric mucosa from three groups of mice: uninfected, infected with H. pylori 26695 strain 98-325 (cagA+ wild-type) or infected with H. pylori mutant strain 99-305 (lacking cag pathogenicity island; cagA-)
2010-11-13 | E-GEOD-21833 | biostudies-arrayexpress
Project description:Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation. Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway. Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities.
2010-11-13 | GSE21833 | GEO
Project description:Microarray Tracking of transposon mutants for a H. pylori mouse colonization screen described in Baldwin DN et al. 2007, I&I, 75(2):??, doi:10.1128/IAI.01176-06. Screen in NSH57 H. pylori strain background. Original 50,000 clone transposon library was plated and patched to make 25 pools of 48 clones. Clones were infected into 4-8 C57Bl/6 mice and stomach bacteria from at least two mice were harvested at 1 week or one month. Semi-random PCR was used to amplify and label the DNA next to the transposon insertion from the input (Cy3) and output pool (Cy5) genomic DNA for each array. Two arrays were done per mouse. One array labeled from the left side of transposon (primers S, 2C) and one array labeled from the right side of the transposon (primers N3, 2C). Transposon insertions were defined by spots with signal four standard deviations above background in both arrays. We also counted insertions where two adjacent gene spots (after arranging the data in genome order) gave signal from the two different sides of the transposon (but not both).
2006-12-15 | E-SMDB-3900 | biostudies-arrayexpress