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

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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.