Type VI secretion
The type VI secretion system (T6SS) is a complex protein export pathway present in hundreds of known bacterial species. Our laboratory discovered that this pathway is utilized by bacteria to deliver toxin and effector proteins to neighboring bacterial cells. An interesting facet of the T6SS is that it targets cells of its own kind in addition to those of other species. Specialized cognate immunity proteins protect organisms against their own toxins.
A) Regulation – As a cell contact-dependent process that is energy intensive, the T6SS is tightly regulated. This is multifactorial, occurring at the transcriptional, translational and posttranslational levels. Our work has predominantly focused on posttranslational regulation governed by a eukaryotic-like signaling cascade. Recently, we identified a second, independently operating pathway.
B) Effectors – The activity of a secretion system is defined by its substrates. Using both proteomic and bioinformatic approaches, we have identified new families of T6S effectors. A major objective of our work in this area is to define the activities of these effectors at a molecular level under physiological conditions.
C) Structure – Currently little is known structurally about the T6SS, including its individual components, its effectors, and its ultrastructure. We have dissected the structure-function mechanism of one T6S immunity protein, and we are currently pursuing high-resolution structures of other T6S components.
D) Pathogenesis – T6SSs are widespread among Gram-negative bacteria, including those that commonly exist in human polymicrobial communities. We are exploring the hypothesis that antagonistic interactions mediated by the T6SS could influence disease outcome. We are also analyzing the role of eukaryotic cell targeting T6SSs in infection.