Grant: Operating Grant

Bacteria secrete toxins, proteases and other virulence factors in order to propagate and promote infection. Our research addresses how these bacterial weapons are transported across membranes. In bacteria, this process relies on a sophisticated membrane-embedded transporter called a "translocon", which opens and closes like a gate-keeper. To study the working mechanism of the translocon, we reconstitute the biological translocation process in artificial membranes, such as liposomes and nanodiscs. In this proposal, we will determine how the different parts of the translocon interact with each other and how they cooperate to move their protein cargos across the bacterial cell membrane. Because this work touches on two vital aspects of bacterial virulence - protein secretion and membrane biogenesis - our studies have fundamental applications that may lead to new drug discoveries. For example, we have found that keeping the translocon's gate in the open state leads to bacterial cell death. Building off of this initial finding, we will screen thousands of different small molecules to find the ones that can stop the function of the translocon, and therefore display antibiotic effect.