{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:21:41Z","timestamp":1762341701891,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["W_1213"],"award-info":[{"award-number":["W_1213"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Background: Helicobacter pylori (Hp) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells. Methods: B cells were infected with Hp isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay. Results: Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs. Conclusions: The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA.<\/jats:p>","DOI":"10.3390\/toxins13090592","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:09:39Z","timestamp":1629842979000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Helicobacter pylori CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1579-7916","authenticated-orcid":false,"given":"Sebastian","family":"Diechler","sequence":"first","affiliation":[{"name":"Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca E.","family":"Chichirau","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-6620","authenticated-orcid":false,"given":"Gernot","family":"Posselt","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0975-2607","authenticated-orcid":false,"given":"Dionyssios N.","family":"Sgouras","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 115 21 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7011-6162","authenticated-orcid":false,"given":"Silja","family":"Wessler","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria"},{"name":"Cancer Cluster Salzburg, Allergy-Cancer-BioNano Research Centre, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1053\/j.gastro.2015.09.004","article-title":"Pathobiology of Helicobacter pylori-Induced Gastric Cancer","volume":"150","author":"Amieva","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/mmi.13707","article-title":"Subversion of host kinases: A key network in cellular signaling hijacked by Helicobacter pylori CagA","volume":"105","author":"Tegtmeyer","year":"2017","journal-title":"Mol. 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