Molecular Mechanism for Targeting a Self-Identity Protein to the Type VI System in Proteus Mirabilis

Abstract

Within a bacterial community, cells can use proteins or small molecules to exchange information that influences the group’s behavior. While small molecules, like quorum sensing signals, tend to be freely diffusible, proteins are transported through the cell envelope by a variety of secretion systems. The type VI secretion system (T6S) is widely conserved across Gram-negative bacteria and is used to transport proteins of a variety of sizes and functions. How protein substrates are targeted to the T6S machinery for exchange is poorly understood. The gut-residing opportunistic pathogen, Proteus mirabilis, relies on the secretion of a protein, IdsD, via the T6S, to exchange self-identity information between cells. Interactions between IdsD and its binding partner, IdsE, in a recipient cell regulate self recognition behaviors. Self (clonal) populations merge while non-self populations form a macroscopic boundary in between them. The goal of my thesis research was to understand how IdsD is regulated through the transport process. Using biochemical, genetic and imaging approaches, I interrogated the hypothesis that IdsD is regulated through interactions with T6S-associated proteins. This research led us to propose a model wherein a proposed-chaperone, IdsC, regulates IdsD prior to secretion. Understanding the pre-transport molecular regulation of IdsD provides us with novel insights into how macromolecular protein complexes can regulate the transcellular communication of information to influence cellular behavior, such as P. mirabilis population dynamics within natural host environments.