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Title: Quorum Sensing Across Bacterial and Viral Domains
Authors: Duddy, Olivia
Advisors: Bassler, Bonnie L
Contributors: Molecular Biology Department
Keywords: Autoinducer
Quorum Sensing
Vibrio cholerae
Subjects: Microbiology
Molecular biology
Issue Date: 2023
Publisher: Princeton, NJ : Princeton University
Abstract: Quorum sensing (QS) is a microbial signaling process that bacteria use to orchestrate collective behaviors. QS relies on the production, release, detection, and response to extracellular signaling molecules called autoinducers (AI). Recent studies demonstrate that bacteria-infecting viruses, called phages, also employ chemical communication to regulate collective activities. Phage-mediated QS signaling and phage eavesdropping on bacterial QS signaling could drive bacteria-phage interactions, possibly contributing to mechanisms that shape both phage and bacterial biology. In infectious Vibrio species, like Vibrio cholerae, the QS receptor and transcriptional activator, called VqmA, binds the AI, 3,5-dimethyl-pyrazin-2-ol (DPO), and the complex activates transcription of vqmR encoding the VqmR small RNA. VqmR represses virulence and biofilm formation at high-cell density, promoting dissemination from the host. Surprisingly, DPO also regulates lysis-lysogeny transitions in the vibriophage VP882. Specifically, phage VP882 encodes a VqmA receptor, called VqmAPhage. VqmAPhage binds DPO to activate expression of the phage gene qtip. Qtip launches the phage lytic program and kills the V. cholerae host at high-cell density. While bacterial VqmA activates expression of vqmR, it cannot activate qtip expression. Curiously, by contrast, VqmAPhage activates qtip expression and also vqmR. DPO is produced by many bacteria, including gut microbiota, whereas only Vibrios and phage VP882 harbor VqmA. Thus, DPO controls V. cholerae QS, mediates V. cholerae-bacteriophage infection, and drives V. choleraeĀ¬-gut microbiota interactions. In this thesis, I determine how VqmA proteins discriminate among ligands to enable robust signaling. I describe the mechanism driving VqmAPhage interference in host QS. Next, I study the native Vibrio host of phage VP882, an isolate of Vibrio parahaemolyticus, and find that phage VP882 virulence is sensitive to all host V. parahaemolyticus QS circuits. Additional chapters are devoted to identifying novel phage lysis-lysogeny regulatory components, independent of the canonical SOS response pathway. In the final chapter, I determine that a phage-encoded LuxR receptor detects non-cognate acyl-homoserine lactone AIs, and the consequence of this is repression of phage LuxR transcriptional activity, thereby protecting the host from lysis. Collectively, my work defines mechanisms of interkingdom chemical communication, and suggests that novel therapeutics can be designed to target both bacteria-specific and phage-specific signaling activities.
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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