<kbd id="no9ls5rn"></kbd><address id="no9ls5rn"><style id="no9ls5rn"></style></address><button id="no9ls5rn"></button>

              <kbd id="jyn6gvil"></kbd><address id="jyn6gvil"><style id="jyn6gvil"></style></address><button id="jyn6gvil"></button>

                      <kbd id="1yxlqexq"></kbd><address id="1yxlqexq"><style id="1yxlqexq"></style></address><button id="1yxlqexq"></button>

                              <kbd id="kkek1egu"></kbd><address id="kkek1egu"><style id="kkek1egu"></style></address><button id="kkek1egu"></button>

                                      <kbd id="z78asujn"></kbd><address id="z78asujn"><style id="z78asujn"></style></address><button id="z78asujn"></button>

                                              <kbd id="ev2lza9j"></kbd><address id="ev2lza9j"><style id="ev2lza9j"></style></address><button id="ev2lza9j"></button>

                                                      <kbd id="2rxhk3e8"></kbd><address id="2rxhk3e8"><style id="2rxhk3e8"></style></address><button id="2rxhk3e8"></button>

                                                              <kbd id="yhgbmj24"></kbd><address id="yhgbmj24"><style id="yhgbmj24"></style></address><button id="yhgbmj24"></button>

                                                                      <kbd id="spzfldo4"></kbd><address id="spzfldo4"><style id="spzfldo4"></style></address><button id="spzfldo4"></button>

                                                                          學術動態

                                                                          當前位置: 首頁 / 學術動態 / 正文

                                                                          【科研動態】我院範紅結新濠天地團隊在豬鏈球菌2型致腦膜腦炎機制研究中取得新突破

                                                                          發佈人: 潘溪     發佈日期: 2018-06-11    瀏覽次數:

                                                                                  20186月 ,細菌學研究國際頂級期刊Cellular Microbiology在線發表了澳门新濠天地-游戏首页範紅結新濠天地團隊在豬鏈球菌2型(SS2)致病機理研究領域所取得的突破性成果:The serine/threonine protein kinase of Streptococcus suis serotype 2 affects the ability of the pathogen to penetrate the blood brain barrier。

                                                                          SS2是一種重要的人獸共患病原菌 ,除嚴重危害養豬業的發展外,於1998年、2005年分別在江蘇、四川造成嚴重的公共衛生問題,引起重大的人員傷亡 。SS2能引起人、豬發生腦膜腦炎  ,但機制不明 。該團隊在國家“973計劃、國家重點研發計劃等項目的資助下 ,劉瑞、李唯一兩位博士研究生利用轉座子誘變技術 ,發現SS2絲氨酸/蘇氨酸蛋白激酶系統(STKs/STPs)通過調控E3泛素連接酶(HECTD1) ,降解鼠腦微血管內皮細胞(bEnd.3)緊密連接蛋白claudin-5,增強血腦屏障的通透性 。該研究首次闡明瞭SS2STKs/STPs能降解bEnd.3的緊密連接蛋白 ,解析其降解機制,研究成果有助於進一步闡明SS2的致病機理 ,爲新型藥物靶標的發現及疫苗開發提供了理論指導  。

                                                                           

                                                                           

                                                                                                          SS2STKs/STPs降解bEnd.3緊密連接蛋白claudin-5的機制模式圖

                                                                           

                                                                          Abstract

                                                                          Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes meningitis in humans and pigs. However, the mechanism whereby SS2 crosses the microvasculature endothelium of the brain is not understood. In this study, transposon (TnYLB-1) mutagenesis was used to identify virulence factors potentially associated with invasive ability in pathogenic SS2. A poorly invasive mutant was identified, and was found to contain a TnYLB-1 insertion in the serine/threonine kinase (stk) gene. Transwell chambers containing hBMECs were used to model the blood-brain barrier (BBB). We observed that the SS2 wild-type ZY05719 strain crossed the BBB model more readily than the mutant strain. Hence, we speculated that STK is associated with the ability of crossing blood-brain barrier in SS2. In vitro, compared with ZY05719, the ability of the stk-deficient strain (Δstk) to adhere to and invade both hBMECs and bEnd.3 cells, as well as to cross the BBB, was significantly attenuated. Immunocytochemistry using antibodies against claudin-5 in bEnd.3 cells showed that infection by ZY05719 disrupted BBB tight junction proteins to a greater extent than in infection by Δstk. The studies revealed that SS2 initially binds at or near intercellular junctions and crosses the BBB via paracellular traversal. Claudin-5 mRNA levels were indistinguishable in ZY05719- and Δstk-infected cells. This result indicated that the decrease of claudin-5 was maybe induced by protein degradation. Cells infected by ZY05719 exhibited higher ubiquitination levels than cells infected by Δstk. This result indicated that ubiquitination was involved in the degradation of claudin-5. Differential proteomic analysis showed that E3 ubiquitin protein ligase HECTD1 decreased by 1.5-fold in Δstk-infected bEnd.3 cells relative to ZY05719-infected cells. Together, the results suggested that STK may affect the expression of E3 ubiquitin ligase HECTD1 and subsequently increase the degradation of claudin-5, thus enabling SS2 to traverse the BBB.