دورية أكاديمية
Taurine modulates host cell responses to Helicobacter pylori VacA toxin.
| العنوان: | Taurine modulates host cell responses to Helicobacter pylori VacA toxin. |
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| المؤلفون: | Westland MD; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee, USA., Schrimpe-Rutledge AC; Department of Chemistry and Center for Innovative Technology, Vanderbilt University , Nashville, Tennessee, USA., Codreanu SG; Department of Chemistry and Center for Innovative Technology, Vanderbilt University , Nashville, Tennessee, USA., Sherrod SD; Department of Chemistry and Center for Innovative Technology, Vanderbilt University , Nashville, Tennessee, USA., McLean JA; Department of Chemistry and Center for Innovative Technology, Vanderbilt University , Nashville, Tennessee, USA., McClain MS; Department of Medicine, Vanderbilt University School of Medicine , Nashville, Tennessee, USA.; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center , Nashville, Tennessee, USA., Cover TL; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee, USA.; Department of Medicine, Vanderbilt University School of Medicine , Nashville, Tennessee, USA.; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center , Nashville, Tennessee, USA.; Veterans Affairs Tennessee Valley Healthcare System , Nashville, Tennessee, USA. |
| المصدر: | Infection and immunity [Infect Immun] 2024 Aug 13; Vol. 92 (8), pp. e0022424. Date of Electronic Publication: 2024 Jul 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| مواضيع طبية MeSH: | Taurine*/metabolism , Taurine*/analogs & derivatives , Bacterial Proteins*/metabolism , Bacterial Proteins*/genetics , Helicobacter pylori*/metabolism, Humans ; Helicobacter Infections/microbiology ; Helicobacter Infections/metabolism ; Cell Line ; Host-Pathogen Interactions ; Metabolomics |
| مستخلص: | Colonization of the human stomach with Helicobacter pylori strains producing active forms of the secreted toxin VacA is associated with an increased risk of peptic ulcer disease and gastric cancer, compared with colonization with strains producing hypoactive forms of VacA. Previous studies have shown that active s1m1 forms of VacA cause cell vacuolation and mitochondrial dysfunction. In this study, we sought to define the cellular metabolic consequences of VacA intoxication. Untargeted metabolomic analyses revealed that several hundred metabolites were significantly altered in VacA-treated gastroduodenal cells (AGS and AZ-521) compared with control cells. Pathway analysis suggested that VacA caused alterations in taurine and hypotaurine metabolism. Treatment of cells with the purified active s1m1 form of VacA, but not hypoactive s2m1 or Δ6-27 VacA-mutant proteins (defective in membrane channel formation), caused reductions in intracellular taurine and hypotaurine concentrations. Supplementation of the tissue culture medium with taurine or hypotaurine protected AZ-521 cells against VacA-induced cell death. Untargeted global metabolomics of VacA-treated AZ-521 cells or AGS cells in the presence or absence of extracellular taurine showed that taurine was the main intracellular metabolite significantly altered by extracellular taurine supplementation. These results indicate that VacA causes alterations in cellular taurine metabolism and that repletion of taurine is sufficient to attenuate VacA-induced cell death. We discuss these results in the context of previous literature showing the important role of taurine in cell physiology and the pathophysiology or treatment of multiple pathologic conditions, including gastric ulcers, cardiovascular disease, malignancy, inflammatory diseases, and other aging-related disorders. Competing Interests: The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | BX004447 U.S. Department of Veterans Affairs (VA); T32 AI138932 United States AI NIAID NIH HHS; AI039657, AI118932, CA116087 HHS | National Institutes of Health (NIH); R01 AI118932 United States AI NIAID NIH HHS; R01 AI039657 United States AI NIAID NIH HHS; I01 BX004447 United States BX BLRD VA; U2C DK119886 United States DK NIDDK NIH HHS; P01 CA116087 United States CA NCI NIH HHS; OT2 OD030544 United States OD NIH HHS |
| فهرسة مساهمة: | Keywords: bacterial protein toxin; cell death; gastric cancer; metabolomics; peptic ulcer disease |
| المشرفين على المادة: | 1EQV5MLY3D (Taurine) 0 (VacA protein, Helicobacter pylori) 0 (Bacterial Proteins) 5L08GE4332 (hypotaurine) |
| تواريخ الأحداث: | Date Created: 20240708 Date Completed: 20240813 Latest Revision: 20240815 |
| رمز التحديث: | 20240815 |
| مُعرف محوري في PubMed: | PMC11320975 |
| DOI: | 10.1128/iai.00224-24 |
| PMID: | 38975764 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5522 |
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| DOI: | 10.1128/iai.00224-24 |