Grant: Operating Grant

The first step in any bacterial infection is attachment of the bacteria to their hosts, or to medical devices such as contact lenses or catheters. Many harmful bacteria use long sticky hair-like filaments called type IV pili for this purpose. Type IV pili are unique because they can be repeatedly extended and retracted, similar to a grappling hook or fishing line. Retraction of the pili pulls the bacteria forward, allowing them move away from the first point of contact and thus spreading the infection (see the movement caused by pilus retraction here: http://youtu.be/yGMSQNBDq48). The bacteria may also use their type IV pili as 'whiskers' to sense when they become attached to something, telling them that it's the right time to produce other factors that contribute to the infection. Without type IV pili, the bacteria are crippled because they can't stick, can't move and can't sense that they are near a suitable surface. We are studying the complex machinery that is used to extend and retract the pili. We want to know what the machine looks like in three dimensions and how its pieces fit together; how the bacteria construct these machines at the ends of the cells and brace them against the extraordinary forces caused by retraction; and how the motor responsible for extension and retraction of the pili works. This information will allow us to design ways to disrupt pilus formation and thereby impair the bacteria's ability to cause infections.