Autoinducer-2 Quorum Sensing Regulation of Bacterial Colonization and Population Distribution in the Zebrafish Intestine

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2021-04-29

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University of Oregon

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Quorum sensing is a mode of bacterial communication that relies on the production and secretion of signaling molecules known as autoinducers. Group-wide detection of autoinducers gives rise to collective gene expression patterns that make coordinated group behaviors possible. Behaviors vary across bacterial species but often include: secretion of virulence factors, changes in motility, and biofilm formation. While many autoinducers exhibit high specificity and are used to foster intraspecies communication, one molecule known as Autoinducer-2 (AI-2) is produced and detected by numerous bacterial species. Interestingly, while AI-2 is known to mediate aggregation and biofilm formation of bacteria through the traditional gene regulatory mechanisms, it uniquely can also do so through the use of chemotaxis signaling. For example, Helicobacter pylori perceives AI-2 as a chemorepellent and in turn this chemorepulsion response results in cell dispersal from biofilms. Conversely, in Escherichia coli AI-2 induces cell aggregation via gene expression changes and by serving as a chemoattractant that recruits cells to aggregates. Currently much of the research involving AI-2 has been carried out in monoculture in vitro biofilms and has focused on the role of AI-2 as a mediator of biofilm formation and biofilm membership. Here we investigate the role of AI-2 in colonization and spatial distribution of bacterial communities inside an animal host. To address this we colonized larval zebrafish with wild type E. coli, an AI-2 synthesis mutant luxS, or an AI-2 signaling mutant lsrR. We then used a combination of plate based assays and live imaging to determine the abundance and spatial distribution of the gut bacteria. We observed that in a mono-association, E. coli mutants lacking the ability to produce or detect AI-2 showed increased intestinal abundance. Additionally, we observed differing spatial localizations between populations of luxS bacteria that had been untreated or treated with AI-2. Populations exposed to AI-2 localized more distally along the axis of the intestine, consistent with increased displacement. Further, we showed that native gut bacteria of the zebrafish exhibit analogous responses to AI-2, indicating that interspecies AI-2 signaling could play an important role in microbiome composition and biogeography. This dissertation includes previously unpublished co-authored material.

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