The Synergistic Role of Tip α, Nucleolin and Ras in Helicobacter pylori Infection Regulates the Cell Fate Towards Inflammation or Apoptosis

Mahant, Shweta; Chakraborty, Amlan; Som, Anup; Mehra, Shubham; Das, Kunal; Mukhopadhyay, Asish K.; Gehlot, Valentina; Bose, Sudeep; Das, Rajashree

doi:10.1007/s00284-021-02626-2

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Mahant et al have used computer modeling to develop a model in which Tipα binding and internalization with nucleolin activates the Ras pathway leading to downstream NF-κB activity promoting inflammation. ( Mahant et al, 2021 ). However, their model supports a role for Tipα monomers to interact with nucleolin in its inactive state which leads to proliferation, which creates an environment that supports hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Helicobacter pylori Infection

et al. 2022

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Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach leading to the development of chronic gastritis, peptic ulcers and gastric adenocarcinoma. A combination of host, environment and bacterial virulence factors contribute to disease development. The H. pylori TNFα inducing protein (Tipɑ) is a virulence factor shown to induce multiple pro-inflammatory cytokines in addition to TNFα in vitro. The goal of the present study was to elucidate the role of Tipα in promoting inflammation in vivo and to identify the molecular pathways associated with Tipα associated virulence. Mice were infected with wild-type Sydney strain (SS1) or a tipα mutant (Δtipα) for 1 month and 4 months. We also completed a second 4 months infection including a 1:1 SS1 to Δtipα co-infected group in addition to SS1 and Δtipα infected groups. The expression of TNFα, and KC were significantly higher in the SS1 infected group compared to both uninfected control (naïve) and Δtipα groups. Mice infected with Tipα expressing SS1 induced more severe histological gastritis and developed hyperplasia compared to Δtipα infected mice. Microarray analysis of gastric epithelial cells co-cultured with recombinant Tipα (rTipα) demonstrates up-regulation of the NFκB pathway. This data suggest Tipα plays an important role in H. pylori induced inflammation.

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Section: Discussionmentioning

confidence: 99%

The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Helicobacter pylori Infection

et al. 2022

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“…Moreover, its overexpression has been related to the development of gastric cancer. Tip-alpha is an exotoxin that penetrates cells and induces the production of tumor necrosis factor alpha[ 53 ]. HP053 protein could have a similar function because probable posttranslational modification sites related to bacterial pathogenesis were also found.…”

Section: Discussionmentioning

confidence: 99%

HP0953 hypothetical protein overexpresses and localization as virulence factor from Helicobacter pylori during infection to gastric epithelium cells

Arteaga-Resendiz¹,

Rodea²,

Ribas‐Aparicio³

et al. 2022

WJG

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BACKGROUND The high prevalence and persistence of Helicobacter pylori ( H. pylori ) infection, as well as the diversity of pathologies related to it, suggest that the virulence factors used by this microorganism are varied. Moreover, as its proteome contains 340 hypothetical proteins, it is important to investigate them to completely understand the mechanisms of its virulence and survival. We have previously reported that the hypothetical protein HP0953 is overexpressed during the first hours of adhesion to inert surfaces, under stress conditions, suggesting its role in the environmental survival of this bacterium and perhaps as a virulence factor. AIM To investigate the expression and localization of HP0953 during adhesion to an inert surface and against gastric (AGS) cells. METHODS Expression analysis was performed for HP0953 during H. pylori adhesion. HP0953 expression at 0, 3, 12, 24, and 48 h was evaluated and compared using the Kruskal-Wallis equality-of-populations rank test. Recombinant protein was produced and used to obtain polyclonal antibodies for immunolocalization. Immunogold technique was performed on bacterial sections during adherence to inert surfaces and AGS cells, which was analyzed by transmission electron microscopy. HP0953 protein sequence was analyzed to predict the presence of a signal peptide and transmembrane helices, both provided by the ExPASy platform, and using the GLYCOPP platform for glycosylation sites. Different programs, via , I-TASSER, RaptorX, and HHalign-Kbest, were used to perform three-dimensional modeling. RESULTS HP0953 exhibited its maximum expression at 12 h of infection in gastric epithelium cells. Immunogold technique revealed HP0953 localization in the cytoplasm and accumulation in some peripheral areas of the bacterial body, with greater expression when it is close to AGS cells. Bioinformatics analysis revealed the presence of a signal peptide that interacts with the transmembrane region and then allows the release of the protein to the external environment. The programs also showed a similarity with the Tip-alpha protein of H. pylori . Tip-alpha is an exotoxin that penetrates cells and induces tumor necrosis factor alpha production, and HP0953 could have a similar function as posttranslational modification sites were found; modifications in turn require enzymes located in eukaryotic cells. Thus, to be functional, HP0953 may necessarily need to be translocated inside the cell where it can trigger different mechanisms producing cellular damage. CONCLUSION The location of HP0953 around infected cells, the probable posttranslational modifications, and its similarity to an exotoxin suggest that this protein is a virulence factor.

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“…A NanoDrop® ND1000 spectrophotometer was used to quantify RNA concentration 29 . After RNA extraction, 1 μg of extracted material was used for cDNA synthesis by randomhexamers and the Revert Aid First Strand cDNA Synthesis kit (Thermo Fisher Scientific Inc., USA) according to the protocol supplied by the manufacturer 30 .…”

Section: Extraction Of Total Rna and Semiquantitative Rt-pcrmentioning

confidence: 99%

Impact of Infection With Helicobacter Pylori on Interleukin-10 Mrna Expression in Stomach Mucosa

Amin

Hassan²,

Elgendy³

et al. 2022

Bulletin of Pharmaceutical Sciences. Assiut

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The immuno-regulatory cytokine interleukin 10 (IL-10) is important in reducing the inflammatory response during H. pylori infection. The goal of our study was to explain how H.pylori infection affects mucosal IL-10 mRNA expression. This study included seventy-three patients suffering from gastroduodenal disorders admitted to Assiut University Hospitals, (35 (47.95%) were males, and 38 (52.05%) were females). Three antral biopsies were obtained from each patient during endoscopic examination. Two invasive tests (Rapid urease test (RUT) and polymerase chain reaction (PCR)) were performed for the detection of H. pylori infection in all participants. Real time PCR (RT-PCR) was performed for determination of IL-10 mRNA expression. Results of RUT and PCR indicated that 60.27% of patients were H. pylori infected. Our results showed that patients positive for H. pylori had significantly higher IL10 mRNA expression than H. pylori-negative patients. Finally, overexpression of IL-10 during H. Pylori infection may be implicated in the downregulation of excessive immune response.

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The Synergistic Role of Tip α, Nucleolin and Ras in Helicobacter pylori Infection Regulates the Cell Fate Towards Inflammation or Apoptosis

Cited by 5 publications

References 32 publications

The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Helicobacter pylori Infection

The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Helicobacter pylori Infection

HP0953 hypothetical protein overexpresses and localization as virulence factor from Helicobacter pylori during infection to gastric epithelium cells

Impact of Infection With Helicobacter Pylori on Interleukin-10 Mrna Expression in Stomach Mucosa

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