Functional analysis of the Shigella flexneri type III secretion system distal needle tip complex

许多致病细菌通过使用一种复杂的机器来攻击我们身体的细胞，这种机器旨在将细菌毒素直接注入被攻击的细胞。这台机器通过使用从细菌表面伸出的微小空心针直接接触目标细胞。细胞和针头之间的接触开启了细菌内的机器，这样细菌毒素就可以穿过针头注射到细胞中。我们想研究这根针的详细结构，特别是它的外部尖端，以帮助我们了解细菌如何知道针已经接触到合适的宿主细胞。然后，我们想了解针尖是如何改变自身插入细胞并允许相对较大的细菌毒素通过针的狭窄中央通道的。我们希望，对这一系统的良好理解将提出干扰这一进程的新方法。在抗生素耐药性越来越快的时候，这些知识可能会导致新型抗菌剂和疫苗的最终设计。

Many disease-causing bacteria attack the cells our bodies by using a complex machine designed to inject bacterial toxins directly into the attacked cell. This machine directly contacts the targeted cell by using a tiny hollow needle that projects from the surface of the bacterium. Contact between the cell and the needle switches on the machine within the bacterium so that bacterial toxins travel through the needle and are injected into the cell. We want to study the detailed structure of this needle, and in particular of its external tip, to help us understand how the bacterium knows that the needle has touched a suitable host cell. We then want to understand how the needle tip alters itself to insert into the cell and allow passage of the relatively large bacterial toxins through the narrow central channel of the needle. We hope that a good understanding of this system will suggest new ways to interfere with the process. Such knowledge may lead to the eventual design of novel antimicrobials and vaccines at a time when antibiotic resistance is increasing ever faster.