幽門螺旋桿菌 (Helicobacter pylori，縮寫H. pylori)是屬於螺旋狀的格蘭氏陰性菌，世界上超過50%的人都受過此菌的感染且被證實會造成消化性潰瘍、胃淋巴瘤等胃部相關疾病有關。幽門螺旋桿菌感染的過程中，巨噬細胞會產生先天性免疫反應造成胃黏膜發炎或傷害。此外，先前的研究指出幽門螺旋桿菌可以延緩巨噬細胞的清除及在細胞內短暫存活二十四小時。因此，致病菌與宿主細胞的交互作用影響了疾病的形成。於是找出細菌與細胞在早期接觸時彼此分泌去影響對方的蛋白質，有助於了解整體的致病機制。本研究收集幽門螺旋桿菌感染人類單核球細胞後的培養液進行分析，以膠體電泳將培養液中的蛋白質分離，且以影像分析軟體找出感染後有差異的蛋白帶，將這些表現量有差異的蛋白質帶經由串聯式液相層析質譜儀分析與資料庫比對鑑定出蛋白質的身分，再以西方墨點法確認蛋白質的表現量，且以共軛焦顯微鏡與流式細胞儀來進行功能性的驗證。從膠體電泳圖的結果顯示在幽門螺旋桿菌感染人類單核球細胞後有15個表現量有差異的蛋白質帶，這些差異的蛋白質帶一共鑑定出31個蛋白質，其中11個是細胞的蛋白質而20是細菌的蛋白質。本研究找出幽門螺旋桿菌分泌出的Elongation factor-tu (EF-Tu) 來進一步驗證，西方點墨法的結果顯示EF-Tu在感染後的培養液中表現量會較單獨培養菌時高出3倍，且又感染細菌上清液的細胞，利用共軛焦顯微鏡可以觀察到EF-Tu會在THP-1細胞膜上，以流式細胞儀發現到處理過細菌上清液的細胞其表面的EF-Tu螢光會增加。總結上述，本研究發現EF-Tu在幽門螺旋桿菌與人類單核球細胞感染過程中表現量有增加的現象且在致病過程中可能是一個附著因子，此外，附著性在許多致病菌在致病的過程中是相當重要的能力。本研究的結果可以得到更多的知識幫助了解宿主細胞與細菌之間致病的機制。

Helicobacter pylori (H.pylori) is a gram-negative, spiral-shaped bacterium that infects over 50% of human population and may cause gastric, peptic ulcer, or gastric malignancies. After H. pylori infection, innate immune responses were induced by H. pylori in macrophages, contributing to mucosal inflammation and damage. Previous study has reported that H. pylori can avoid macrophage clearance and proliferate in macrophage for 24 hours. Thus, host-pathogen interaction determined development of disease. To identify the secreted proteins between bacteria and host cell early contact is conducive to understand the mechanism of pathogenesis. This study utilized co-culture system of H. pylori and monocyte (THP-1 cells) for collection of the conditioned media (CM) to analysis. The proteins of CM were separated by SDS-PAGE and the differential expression protein bands were analyzed by image analysis software. The differential expression proteins were identified by liquid chromatography tandem mass spectrometry analysis and database search. The protein expression was confirmed by western blot, and the functional validation was used by confocal microscopy and flow cytometry. SDS-PAGE analysis showed 15 differential expression bands in co-culture of bacteria and cells. A total of 31 proteins were identified, among them 11 proteins belonged to THP-1 cells and 20 proteins belonged to H. pylori. We identified a potential virulence factor of H. pylori, Elongation factor-tu (EF-Tu), for further confirmation. There was 3-fold higher protein expression of EF-Tu in co-culture system than only H. pylori. Furthermore, EF-Tu was observed on the surface THP-1 cells by confocal microscopy treating CM of H. pylori. The result of flow cytometry demonstrated that the fluorescent intensity of EF-Tu on the THP-1 cells increased after adding CM of H. pylori. To summarize, we found that EF-TU is up-regulated during host-pathogen interaction and is a potential adhesive factor. Besides, adhesive activity is important for pathogenesis in many pathogens. The results of this study may provide a further knowledge of host-pathogen interaction in the pathogenesis.

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