Signaling in symbiosis: The RNA signature of local and systemic interactions between partners

Abstract

Over the course of evolution, animals and bacteria have formed mutually beneficial partnerships, often characterized by an exchange of essential or fitness-enhancing goods and services, such as nutrients or safety. These symbioses, which have numerous effects on host fitness, can significantly impact host development and physiology. This dissertation uses the squid-vibrio symbiosis to examine the biochemical signaling that occurs between symbiotic partners, focusing on RNA-mediated host-microbe interactions. In the symbiosis between the marine bioluminescent bacterium Vibrio fischeri and the squid Euprymna scolopes, the host houses a monospecific association with V. fischeri in an organ specifically adapted to manipulate bacterial bioluminescence. This dissertation begins by describing the profound local and systemic influences of a single symbiont on the gene regulation of host tissues, highlighting the impact of the light-organ symbiosis on host expression networks across developmental time and daily rhythms. We found that the light produced by the bacteria is the main driver of changes of gene expression both within the light organ and throughout other organs. We next studied the role of bacterial small RNAs (sRNAs) in triggering responses in an animal host. We identified a symbiont sRNA called SsrA that is loaded into outer membrane vesicles (OMVs), and trafficked into the epithelium of the host. We determined that the delivery of SsrA is required to dampen the animal’s immune response, which is necessary for a successful symbiosis. In addition, we found that the absence of this sRNA affects the host at the transcriptional, cellular, and physiological levels, negatively impacting fitness, and ultimately resulting in failure of the association to persist. As the light organ undergoes vast changes of gene expression in response to colonization by V. fischeri, we next studied the mechanisms of the regulation of host gene expression that orchestrates the main developmental and physiological changes in the light organ. We characterized the E. scolopes miRNA transcriptome as well as the extent of miRNA-mediated post-transcriptional regulation within the host light organ. The resultant miRNA transcriptome of the light organ drives gene expressional networks that both orchestrate developmental changes in symbiotic tissues and adapt the host immune response to integrate the symbiont into its biology.