UC Santa Barbara

Bacteria live in complex microbial communities and must face the constant challenge of limited space and resources. These harsh conditions have driven the evolution of a variety of competition and communications systems that allow bacteria to interact with the surrounding microbes and eukaryotic organisms found in their respective niches. The research presented here focuses on two such systems that Gram-negative bacteria use to deliver toxic effector molecules into neighboring bacteria. The type VI secretion system (T6SS) is a dynamic syringe-like organelle that injects toxic effectors indiscriminately into both prokaryotic and eukaryotic cells. In contrast, CDI systems are restricted to a narrow target range. CDI involves a two-partner secretion system that presents a large exoprotein, CdiA, to the surface of cells. CdiA binds to receptors on target bacteria to facilitate delivery of a toxin derived from its C-terminus.

In the introductory chapter, we will dissect what it known about each of these competition systems, including the toxin activities and delivery pathways of each system. Chapter 2 identifies a novel delivery process of a CDI toxin into Escherichia coli. In chapter 3 we will learn that the CDI system found in uropathogenic E. coli 536 is restricted to intrastrain delivery due to polymorphisms in the receptor proteins it utilizes for delivery. Chapter 4 will characterize novel CDI toxin activity while chapter 5 will explore the motive behind exploiting the metabolic enzyme, CysK, as a cofactor for a CDI toxin’s activity. Finally, chapter 6 will describe the mechanism of toxin delivery in the T6SS found in the opportunistic human pathogen Enterobacter cloacae.

Ultimately, this thesis will explore the repertoire of toxins that are utilized by CDI and T6S systems. Chapters 3 and 5 will challenge the function of CDI as a competition system and suggests its role in kin selection. Lastly, we will examine the potential role of these competition systems in shaping microbial communities.