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The identification and characterization of novel antibacterial compounds via target-based and whole cell screening approaches

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Title: The identification and characterization of novel antibacterial compounds via target-based and whole cell screening approaches
Author(s): Wang, Nora R.
Director of Research: Hergenrother, Paul J.
Doctoral Committee Chair(s): Hergenrother, Paul J.
Doctoral Committee Member(s): van der Donk, Wilfred A.; Silverman, Scott K.; Burke, Martin D.
Department / Program: Chemistry
Discipline: Chemistry
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): antibiotic antibacterial infection resistance Staphylococcus aureus
Abstract: The emergence of multidrug-resistant bacterial infections in both the clinical setting and the community has created an environment in which the development of novel antibacterial compounds is necessary to keep dangerous infections at bay. While the derivatization of existing antibiotics by pharmaceutical companies has so far been successful at achieving this end, this strategy is short-term, and the discovery of antibacterials with novel scaffolds would be a greater contribution to the fight of multidrug-resistant infections. Described herein is the application of both target-based and whole cell screening strategies to identify novel antibacterial compounds. In a target-based approach, we sought small-molecule disruptors of the MazEF toxin-antitoxin protein complex. A lack of facile, continuous assays for this target required the development of a fluorometric assay for MazF ribonuclease activity. This assay was employed to further characterize the activity of the MazF enzyme and was used in a screening effort to identify disruptors of the MazEF complex. In addition, by employing a whole cell screening approach, we identified two compounds with potent antibacterial activity. Efforts to characterize the in vitro antibacterial activities displayed by these compounds and to identify their modes of action are described.
Issue Date: 2011-05-25
URI: http://hdl.handle.net/2142/24451
Rights Information: Copyright 2011 Nora R. Wang
Date Available in IDEALS: 2011-05-25
2013-05-26
Date Deposited: 2011-05
 

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