Mechanisms by which Xenorhabdus nematophila interacts with hosts using integrated -omics approaches

Nearly all organisms exist in proximity to microbes. These microbes perform most of the essential metabolic processes necessary for homeostasis, forming the nearly hidden support system of Earth. Microbial symbiosis, which is defined as the long-term physical association between host and microbes, relies on communication between the microbial community and their host organism. These interactions among higher order organisms (such as animals, plants, and fungi) and their bacteria links metabolic processes between interkingdom consortia. Many questions on microbial behavior within a host remain poorly understood, such as the colonization efficiency among different microbial species, or how environmental context changes their behavior. We can utilize integrated -omics protocols to better characterize these complex interactions from their genetic blueprint to their metabolic functions. Many animal pathogenicity mechanisms are conserved among bacteria species regardless of their host, thus -omics investigations of host-pathogen interactions can be used to better understand the fundamental biology of host-pathogen interactions that subsequently leads to knowledge supporting translational research to mitigate harmful bacterial infections. The focus of this dissertation is to better understand the molecular biology underlying mutualism and antagonism using a simplified animal-microbe symbiosis model that I argue is foundational for understanding larger, more complex microbiome studies. I aim to elucidate the molecular mechanisms that confer the Xenorhabdus-Steinernema animal-microbe symbiosis using integrated -omics based approaches. This is a simplified one host, one microbe system with aspects of the lifecycle pertaining to mutualism (Xenorhabdus bacteria mutualistic colonization of Steinernema nematodes to find prey) and antagonism (Xenorhabdus release from Steinernema within prey insects to kill them, convert the insect cadaver nutrients, and reproduction of nematodes and bacteria). For this dissertation, I discuss the study of this system as two parts of the Xenorhabdus lifecycle. In Chapter 2, I focus on the broad chemical ecology of the Xenorhabdus-Steinernema system by investigating how the nematode-bacterium pair metabolically alters the host chemical environment. In Chapter 3, I seek to better understand the specific biochemical mechanisms by which Xenorhabdus bacteria associates with Steinernema nematodes, with implications of this research extending to human pathogenic Proteobacteria. As such, the introductory chapter (Chapter 1) was constructed as a foundation for these studies, presenting where the “symbiomics” field has come and where it is likely going.