Simon Fraser University Department of Biological Sciences Shrum Science Centre Room B8276 Burnaby, BC, V5A 1S6.
Sci Rep. 2011;1:192. doi: 10.1038/srep00192. Epub 2011 Dec 14.
Francisella tularensis are highly infectious microbes that cause the disease tularemia. Although much of the bacterial burden is carried in non-phagocytic cells, the strategies these pathogens use to invade these cells remains elusive. To examine these mechanisms we developed two in vitro Francisella-based infection models that recapitulate the non-phagocytic cell infections seen in livers of infected mice. Using these models we found that Francisella novicida exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We also found that the clathrin accessory proteins AP-2 and Eps15 co-localized with invading Francisella novicida as well as the Francisella Live Vaccine Strain (LVS) during hepatocyte infections. Interestingly, caveolin, a protein involved in the invasion of Francisella in phagocytic cells, was not required for non-phagocytic cell infections. These results demonstrate a novel endocytic mechanism adopted by Francisella and highlight the divergence in strategies these pathogens utilize between non-phagocytic and phagocytic cell invasion.
土拉弗朗西斯菌是一种高度传染性的微生物，可引起土拉菌病。尽管大部分细菌负荷存在于非吞噬细胞中，但这些病原体入侵这些细胞的策略仍难以捉摸。为了研究这些机制，我们开发了两种基于土拉弗朗西斯菌的体外感染模型，该模型再现了感染小鼠肝脏中观察到的非吞噬细胞感染。使用这些模型，我们发现弗氏柠檬酸杆菌利用网格蛋白和胆固醇依赖性机制进入肝细胞。我们还发现，网格蛋白辅助蛋白 AP-2 和 Eps15 在肝细胞感染期间与入侵的弗氏柠檬酸杆菌以及弗氏活疫苗株（LVS）共定位。有趣的是，参与吞噬细胞中弗朗西斯菌入侵的 caveolin 蛋白对于非吞噬细胞感染并非必需。这些结果表明弗朗西斯菌采用了一种新的胞吞机制，并强调了这些病原体在非吞噬细胞和吞噬细胞入侵中利用策略的差异。
