Delivery of cargo to target cells is fundamentally important for bacterial competitiveness, and many species can deploy a wide variety of systems in pursuit of this goal. One important but poorly understood system, ubiquitous among Gram-negative organisms, involves packaging cargo into small outer membrane vesicles (OMVs). These biological nanoparticles are important in processes ranging from toxin delivery to nucleic acid transfer to cell-cell communication. Despite this, we know comparatively little about how OMVs are formed or how cargo is packaged. Building upon the discovery that the Pseudomonas Quinolone Signal (PQS) stimulates OMV biogenesis in Pseudomonas aeruginosa, we proposed the Bilayer-Couple model to describe a mechanism by which self-produced small molecules interact with the outer membrane to induce curvature and ultimately OMV formation. Though this model is well supported in P. aeruginosa, it remained unclear whether other organisms produce similar OMV-inducing compounds, and what factors are important for the regulation of this process. Here we describe the development of a tightly controlled experimental system to test the interaction of bacterially produced small molecules with target cells and their effect on OMV biogenesis, the production of OMV promoting factors by multiple bacteria, and several factors governing the process of OMV biogenesis. We also investigate the role of OMVs and small molecule induced (SMI) OMV production in bacterial pathogenesis. Taken together, this work provides an in-depth analysis of a recently described system of virulence and communication between bacterial species.
|Advisor:||Schertzer, Jeffrey W.|
|Commitee:||Grewer, Christof, Marques, Claudia, Sauer, Karin, Tammariello, Steven|
|School:||State University of New York at Binghamton|
|School Location:||United States -- New York|
|Source:||DAI-B 80/11(E), Dissertation Abstracts International|
|Subjects:||Microbiology, Biochemistry, Immunology|
|Keywords:||Cross-species, OMVS, P. aeruginosa, PQS|
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