Jing Lai, Sacheera Angulmaduwa, Myeong-A Kim, Aeryun Kim, Kavinda Tissera, Yong-Joon Cho, Jeong-Heon Cha
{"title":"oipA 相位变异对幽门螺旋杆菌与 IV 型分泌系统相关的毒性表型的影响","authors":"Jing Lai, Sacheera Angulmaduwa, Myeong-A Kim, Aeryun Kim, Kavinda Tissera, Yong-Joon Cho, Jeong-Heon Cha","doi":"10.1111/hel.13140","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p><i>oipA</i>, an outer membrane protein of <i>Helicobacter pylori</i>, is linked to IL-8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of <i>oipA</i> phase variation in modulating the virulence traits of <i>H. pylori</i>, a bacterium strongly associated with the development of gastric cancer.</p>\n </section>\n \n <section>\n \n <h3> Material and Methods</h3>\n \n <p>American clinical isolate AH868 strain for naturally occurring phase variations of the <i>oipA</i> gene, and G27 strain for in vitro–induced phase variations were used to elucidate <i>oipA</i>'s impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL-8 induction.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Using AH868 strain, natural <i>oipA</i> phase variation does not affect cell elongation and IL-8 induction. Interestingly, however, in vitro–induced <i>oipA</i> phase variations in G27 strain uncovered that 9.4% of <i>oipA</i> “Off” transformants exhibit reduced cell elongation while all maintaining consistent IL-8 induction levels. Additionally, complementation of <i>oipA</i> “Off to On” status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of <i>oipA</i> in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among <i>oipA</i> phase variation, cell elongation, and CagA phosphorylation, suggesting that <i>oipA</i> influences the functionality of the Type IV secretion system. Whole-genome sequencing of selected transformants reveals genetic variations in <i>bab</i> paralogue, <i>cagY</i> gene, and other genomic regions, underscoring the complex genetic interactions that shape <i>H. pylori</i>'s virulence.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our research provides new insights into the subtle yet significant role of <i>oipA</i> phase variation in <i>H. pylori</i> pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of <i>H. pylori</i> on human health.</p>\n </section>\n </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 5","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.13140","citationCount":"0","resultStr":"{\"title\":\"Influence of oipA Phase Variation on Virulence Phenotypes Related to Type IV Secretion System in Helicobacter pylori\",\"authors\":\"Jing Lai, Sacheera Angulmaduwa, Myeong-A Kim, Aeryun Kim, Kavinda Tissera, Yong-Joon Cho, Jeong-Heon Cha\",\"doi\":\"10.1111/hel.13140\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p><i>oipA</i>, an outer membrane protein of <i>Helicobacter pylori</i>, is linked to IL-8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of <i>oipA</i> phase variation in modulating the virulence traits of <i>H. pylori</i>, a bacterium strongly associated with the development of gastric cancer.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Material and Methods</h3>\\n \\n <p>American clinical isolate AH868 strain for naturally occurring phase variations of the <i>oipA</i> gene, and G27 strain for in vitro–induced phase variations were used to elucidate <i>oipA</i>'s impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL-8 induction.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Using AH868 strain, natural <i>oipA</i> phase variation does not affect cell elongation and IL-8 induction. Interestingly, however, in vitro–induced <i>oipA</i> phase variations in G27 strain uncovered that 9.4% of <i>oipA</i> “Off” transformants exhibit reduced cell elongation while all maintaining consistent IL-8 induction levels. Additionally, complementation of <i>oipA</i> “Off to On” status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of <i>oipA</i> in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among <i>oipA</i> phase variation, cell elongation, and CagA phosphorylation, suggesting that <i>oipA</i> influences the functionality of the Type IV secretion system. Whole-genome sequencing of selected transformants reveals genetic variations in <i>bab</i> paralogue, <i>cagY</i> gene, and other genomic regions, underscoring the complex genetic interactions that shape <i>H. pylori</i>'s virulence.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our research provides new insights into the subtle yet significant role of <i>oipA</i> phase variation in <i>H. pylori</i> pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of <i>H. pylori</i> on human health.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13223,\"journal\":{\"name\":\"Helicobacter\",\"volume\":\"29 5\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.13140\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Helicobacter\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/hel.13140\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Helicobacter","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hel.13140","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Influence of oipA Phase Variation on Virulence Phenotypes Related to Type IV Secretion System in Helicobacter pylori
Background
oipA, an outer membrane protein of Helicobacter pylori, is linked to IL-8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of oipA phase variation in modulating the virulence traits of H. pylori, a bacterium strongly associated with the development of gastric cancer.
Material and Methods
American clinical isolate AH868 strain for naturally occurring phase variations of the oipA gene, and G27 strain for in vitro–induced phase variations were used to elucidate oipA's impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL-8 induction.
Results
Using AH868 strain, natural oipA phase variation does not affect cell elongation and IL-8 induction. Interestingly, however, in vitro–induced oipA phase variations in G27 strain uncovered that 9.4% of oipA “Off” transformants exhibit reduced cell elongation while all maintaining consistent IL-8 induction levels. Additionally, complementation of oipA “Off to On” status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of oipA in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among oipA phase variation, cell elongation, and CagA phosphorylation, suggesting that oipA influences the functionality of the Type IV secretion system. Whole-genome sequencing of selected transformants reveals genetic variations in bab paralogue, cagY gene, and other genomic regions, underscoring the complex genetic interactions that shape H. pylori's virulence.
Conclusions
Our research provides new insights into the subtle yet significant role of oipA phase variation in H. pylori pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of H. pylori on human health.
期刊介绍：
Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.
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