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

Wang, Nora R.

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https://hdl.handle.net/2142/24451 Copy

Description

Title

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

Author(s)

Wang, Nora R.

Issue Date

2011-05-25T14:25:16Z

Director of Research (if dissertation) or Advisor (if thesis)

Hergenrother, Paul J.

Doctoral Committee Chair(s)

Hergenrother, Paul J.

Committee Member(s)

• van der Donk, Wilfred A.
• Silverman, Scott K.
• Burke, Martin D.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(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.

Graduation Semester

2011-05

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http://hdl.handle.net/2142/24451

Copyright and License Information

Copyright 2011 Nora R. Wang

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