Protein complexes mediate a diverse range of behavior in prokaryotic cells, yet the exact molecular mechanisms explaining how many of these complexes assemble and function remain unknown. This work focuses on understanding the molecular mechanisms of two different protein assemblies responsible for regulating virulence in the opportunistic pathogen Pseudomonas aeruginosa. P. aeruginosa utilizes type IV pili (T4P) to adhere to, and move along, surfaces. Assembly of T4P is powered by a dedicated cytoplasmic ATPase, PilB. The structural study of PilB from a related system (chapter 2) resulted in the formulation of the first model describing the mechanism of force generation resulting from ATP hydrolysis, which explains how T4P are assembled. Chapter 3 focuses on the RetS/GacS interaction, which is responsible for globally regulating virulence in P. aeruginosa. A comprehensive structural study reveals a dynamics of a novel regulatory interaction and the discovery of a potentially universal transmembrane signaling mechanism. / Doctor of Philosophy / Bacteria have threatened human health since the beginning of recorded history. With the development of antibiotics in the early twentieth century, the threat posed by bacterial infection was greatly lessened. However, decades of antibiotic mismanagement has led to the evolution of bacteria which are no longer vulnerable to these antibiotics. In order to combat this rising threat of resistant bacteria, we require a deeper understanding of how bacteria function and cause disease. Proteins play a crucial role in the diseases caused by bacteria, either by directly damaging host cells or regulating the expression of these damaging factors. By increasing our knowledge of the roles played by protein during bacterial infections, it will be possible to create new antibiotics while minimizing the risk of resistance. The work presented here grants a deeper understanding into how proteins work together to allow bacteria to survive inside the human body.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/102298 |
| Date | 15 August 2019 |
| Creators | Mancl, Jordan Michael |
| Contributors | Biological Sciences, Schubot, Florian D., Jensen, Roderick V., Yang, Zhaomin, Scharf, Birgit E. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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