Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins
Helicobacter pylori infection is associated with the development of several gastric diseases including gastric cancer. To reach a long-term colonization in the host stomach, H. pylori employs multiple outer membrane adhesins for binding to the gastric mucosa. However, due to the redundancy of adhesi...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2130650 |
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| author | Kai-Wen Teng Kai-Siang Hsieh Ji-Shiuan Hung Chun-Jen Wang En-Chi Liao Pei-Chun Chen Ying-Hsuan Lin Deng-Chyang Wu Chun-Hung Lin Wen-Ching Wang Hong-Lin Chan Shau-Ku Huang Mou-Chieh Kao |
| author_facet | Kai-Wen Teng Kai-Siang Hsieh Ji-Shiuan Hung Chun-Jen Wang En-Chi Liao Pei-Chun Chen Ying-Hsuan Lin Deng-Chyang Wu Chun-Hung Lin Wen-Ching Wang Hong-Lin Chan Shau-Ku Huang Mou-Chieh Kao |
| author_sort | Kai-Wen Teng |
| collection | DOAJ |
| description | Helicobacter pylori infection is associated with the development of several gastric diseases including gastric cancer. To reach a long-term colonization in the host stomach, H. pylori employs multiple outer membrane adhesins for binding to the gastric mucosa. However, due to the redundancy of adhesins that complement the adhesive function of bacteria, targeting each individual adhesin alone usually achieves nonideal outcomes for preventing bacterial adhesion. Here, we report that key adhesins AlpA/B and BabA/B in H. pylori are modified by glycans and display a two-step molecular weight upshift pattern from the cytoplasm to the inner membrane and from the inner membrane to the outer membrane. Nevertheless, this upshift pattern is missing when the expression of some enzymes related to lipopolysaccharide (LPS) biosynthesis, including the LPS O-antigen assembly and ligation enzymes WecA, Wzk, and WaaL, is disrupted, indicating that the underlying mechanisms and the involved enzymes for the adhesin glycosylation are partially shared with the LPS biosynthesis. Loss of the adhesin glycosylation not only reduces the protease resistance and the stability of the tested adhesins but also changes the adhesin-binding ability. In addition, mutations in the LPS biosynthesis cause a significant reduction in bacterial adhesion in the in vitro cell-line model. The current findings reveal that H. pylori employs a general protein glycosylation system related to LPS biosynthesis for adhesin modification and its biological significance. The enzymes required for adhesin glycosylation rather than the adhesins themselves are potentially better drug targets for preventing or treating H. pylori infection. |
| format | Article |
| id | doaj-art-9a644484816546ee8f6f39b59441d3b4 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-9a644484816546ee8f6f39b59441d3b42025-08-20T02:29:58ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2130650Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesinsKai-Wen Teng0Kai-Siang Hsieh1Ji-Shiuan Hung2Chun-Jen Wang3En-Chi Liao4Pei-Chun Chen5Ying-Hsuan Lin6Deng-Chyang Wu7Chun-Hung Lin8Wen-Ching Wang9Hong-Lin Chan10Shau-Ku Huang11Mou-Chieh Kao12Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei, TaiwanInstitute of Molecular and Cellular Biology, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanNational Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, TaiwanInstitute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, TaiwanHelicobacter pylori infection is associated with the development of several gastric diseases including gastric cancer. To reach a long-term colonization in the host stomach, H. pylori employs multiple outer membrane adhesins for binding to the gastric mucosa. However, due to the redundancy of adhesins that complement the adhesive function of bacteria, targeting each individual adhesin alone usually achieves nonideal outcomes for preventing bacterial adhesion. Here, we report that key adhesins AlpA/B and BabA/B in H. pylori are modified by glycans and display a two-step molecular weight upshift pattern from the cytoplasm to the inner membrane and from the inner membrane to the outer membrane. Nevertheless, this upshift pattern is missing when the expression of some enzymes related to lipopolysaccharide (LPS) biosynthesis, including the LPS O-antigen assembly and ligation enzymes WecA, Wzk, and WaaL, is disrupted, indicating that the underlying mechanisms and the involved enzymes for the adhesin glycosylation are partially shared with the LPS biosynthesis. Loss of the adhesin glycosylation not only reduces the protease resistance and the stability of the tested adhesins but also changes the adhesin-binding ability. In addition, mutations in the LPS biosynthesis cause a significant reduction in bacterial adhesion in the in vitro cell-line model. The current findings reveal that H. pylori employs a general protein glycosylation system related to LPS biosynthesis for adhesin modification and its biological significance. The enzymes required for adhesin glycosylation rather than the adhesins themselves are potentially better drug targets for preventing or treating H. pylori infection.https://www.tandfonline.com/doi/10.1080/19490976.2022.2130650Helicobacter pylorilipopolysaccharideprotein glycosylationouter membrane adhesinBabABabB |
| spellingShingle | Kai-Wen Teng Kai-Siang Hsieh Ji-Shiuan Hung Chun-Jen Wang En-Chi Liao Pei-Chun Chen Ying-Hsuan Lin Deng-Chyang Wu Chun-Hung Lin Wen-Ching Wang Hong-Lin Chan Shau-Ku Huang Mou-Chieh Kao Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins Gut Microbes Helicobacter pylori lipopolysaccharide protein glycosylation outer membrane adhesin BabA BabB |
| title | Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| title_full | Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| title_fullStr | Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| title_full_unstemmed | Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| title_short | Helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| title_sort | helicobacter pylori employs a general protein glycosylation system for the modification of outer membrane adhesins |
| topic | Helicobacter pylori lipopolysaccharide protein glycosylation outer membrane adhesin BabA BabB |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2130650 |
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