The goal of this research is to discern mechanisms by which the environment within the human host are responsible for inducing expression of specific genes of infecting bacteria. The model system to be analyzed is the Vibrio cholerae ToxR regulon, for which a number of parameters that induce gene expression as well as many of the genes involved have been identified. ToxR can be thought of as an integral membrane protein positioned centrally in a regulatory scheme where it receives signals perhaps via small molecules and through protein-protein interactions that allow ultimate control of gene expression through a regulatory cascade. ToxR spans the bacterial cytoplasmic membrane and in this configuration is able to directly activate expression of a number of host specific genes. Some of these gene products are directly involved in allowing the bacteria to colonize and express an ADP-ribosylating exotoxin that stimulates the activity of host membrane adenylate cyclase. Another gene that ToxR activates, toxT, also encodes an activator protein of the AraC family that is cytoplasmically located. In turn, this protein activates additional genes including itself and colonization factors required for maintenance of an infected state. Thus, there is a hierarchy of gene expression that responds to the host to initiate and maintain infection.
Showing the most recent 10 out of 38 publications
