Department of Periodontics, Changsha Stomatological Hospital, Changsha, Hunan, China.
Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, Republic of Korea.
Helicobacter. 2024 Sep-Oct;29(5):e13140. doi: 10.1111/hel.13140.
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.
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.
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.
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.
幽门螺杆菌的外膜蛋白 oipA 与 IL-8 诱导和胃炎症有关，但由于研究结果不一致，其作用仍存在争议。本研究旨在探索 oipA 相位变异在调节幽门螺杆菌（一种与胃癌发展密切相关的细菌）毒力特征中的作用。
使用美国临床分离株 AH868 进行 oipA 基因自然发生的相位变异，以及 G27 株进行体外诱导的相位变异，以阐明 oipA 对关键毒力表型的影响，包括细胞伸长、CagA 磷酸化和 IL-8 诱导。
使用 AH868 株，自然 oipA 相位变异不会影响细胞伸长和 IL-8 诱导。然而，有趣的是，在 G27 株中体外诱导的 oipA 相位变异揭示了 9.4%的 oipA“关闭”转化体表现出细胞伸长减少，而所有转化体保持一致的 IL-8 诱导水平。此外，oipA“关闭”到“开启”状态的互补恢复了 12.5%转化体的细胞伸长表型，突出了 oipA 在维持正常细胞形态中的重要性。至关重要的是，这些细胞伸长的变异与细菌粘附能力的变化无关。此外，该研究表明 oipA 相位变异、细胞伸长和 CagA 磷酸化之间存在相关性，表明 oipA 影响 IV 型分泌系统的功能。选择转化体的全基因组测序揭示了 bab 旁系同源物、cagY 基因和其他基因组区域的遗传变异，强调了塑造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的微妙但重要作用提供了新的见解，强调需要进一步研究探索涉及的复杂分子机制。这种理解为减轻幽门螺杆菌对人类健康的影响开辟了靶向治疗策略的道路。
