Influence of oipA Phase Variation on Virulence Phenotypes Related to Type IV Secretion System in Helicobacter pylori

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Helicobacter Pub Date : 2024-10-23 DOI:10.1111/hel.13140

Jing Lai, Sacheera Angulmaduwa, Myeong-A Kim, Aeryun Kim, Kavinda Tissera, Yong-Joon Cho, Jeong-Heon Cha

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Abstract

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.

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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

背景：幽门螺杆菌的外膜蛋白oipA与IL-8诱导和胃部炎症有关，但由于研究结果不一致，其作用还存在争议。本研究旨在探讨 oipA 相位变异在调节幽门螺杆菌毒力特征中的作用，幽门螺杆菌与胃癌的发生密切相关：利用美国临床分离株AH868和体外诱导的G27来阐明oipA对关键毒力表型（包括细胞伸长、CagA磷酸化和IL-8诱导）的影响：结果：使用 AH868 菌株，天然 oipA 阶段变异不会影响细胞伸长和 IL-8 诱导。但有趣的是，体外诱导 G27 菌株的 oipA 相位变异发现，9.4% 的 oipA "关闭 "转化株表现出细胞伸长率降低，而所有转化株都保持了一致的 IL-8 诱导水平。此外，将 oipA "关闭 "状态补充为 "开启 "状态可恢复 12.5% 转化株的细胞伸长表型，这凸显了 oipA 在维持正常细胞形态方面的重要性。重要的是，细胞伸长的这些变化与细菌粘附能力的变化无关。此外，研究还显示了 oipA 相位变化、细胞伸长和 CagA 磷酸化之间的相关性，表明 oipA 影响了 IV 型分泌系统的功能。对所选转化株的全基因组测序揭示了bab旁系、cagY基因和其他基因组区域的遗传变异，强调了形成幽门螺杆菌毒力的复杂遗传相互作用：我们的研究为 oipA 相位变异在幽门螺杆菌致病性中微妙而重要的作用提供了新的见解，强调了进一步研究探索其中错综复杂的分子机制的必要性。这种认识可以为制定有针对性的治疗策略铺平道路，从而减轻幽门螺杆菌对人类健康的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

审稿时长

2 months

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.