<i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells
Background: <i>Helicobacter pylori</i> (<i>Hp</i>) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the <i>Hp</i> virulence factor cytotoxin-associated gene A...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/9/592 |
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| author | Sebastian Diechler Bianca E. Chichirau Gernot Posselt Dionyssios N. Sgouras Silja Wessler |
| author_facet | Sebastian Diechler Bianca E. Chichirau Gernot Posselt Dionyssios N. Sgouras Silja Wessler |
| author_sort | Sebastian Diechler |
| collection | DOAJ |
| description | Background: <i>Helicobacter pylori</i> (<i>Hp</i>) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the <i>Hp</i> 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 <i>Hp</i> 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. |
| first_indexed | 2024-03-10T07:09:55Z |
| format | Article |
| id | doaj.art-b50555b911f44da88eaa23a85c188f1f |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T07:09:55Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-b50555b911f44da88eaa23a85c188f1f2023-11-22T15:30:39ZengMDPI AGToxins2072-66512021-08-0113959210.3390/toxins13090592<i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B CellsSebastian Diechler0Bianca E. Chichirau1Gernot Posselt2Dionyssios N. Sgouras3Silja Wessler4Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, AustriaDivision of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, AustriaDivision of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, AustriaLaboratory of Medical Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 115 21 Athens, GreeceDivision of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, AustriaBackground: <i>Helicobacter pylori</i> (<i>Hp</i>) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the <i>Hp</i> 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 <i>Hp</i> 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.https://www.mdpi.com/2072-6651/13/9/592<i>Helicobacter pylori</i>CagAEPIYA motifsB cells |
| spellingShingle | Sebastian Diechler Bianca E. Chichirau Gernot Posselt Dionyssios N. Sgouras Silja Wessler <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells Toxins <i>Helicobacter pylori</i> CagA EPIYA motifs B cells |
| title | <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells |
| title_full | <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells |
| title_fullStr | <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells |
| title_full_unstemmed | <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells |
| title_short | <i>Helicobacter pylori</i> CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells |
| title_sort | i helicobacter pylori i caga epiya motif variations affect metabolic activity in b cells |
| topic | <i>Helicobacter pylori</i> CagA EPIYA motifs B cells |
| url | https://www.mdpi.com/2072-6651/13/9/592 |
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