Investigation of the YefM-YoeBSa toxin-antitoxin systems as novel antibacterial targets

Larson, Amy

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https://hdl.handle.net/2142/44445 Copy

Description

Title

Investigation of the YefM-YoeBSa toxin-antitoxin systems as novel antibacterial targets

Author(s)

Larson, Amy

Issue Date

2013-05-24T22:16:25Z

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

Hergenrother, Paul J.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• toxin-antitoxin system
• antibacterial

Abstract

The rise and spread of drug-resistant pathogens has created a critical need for the continued discovery and development of new antibacterial compounds. Bacterial toxin-antitoxin (TA) systems consist of a toxin capable of arresting cell growth and an antitoxin that binds to and inhibits the toxin under normal circumstances. Cellular stress causes a shift in the toxin/antitoxin ratio to favor the free toxin, which is released to act on its cellular target and arrest growth. TA systems therefore present potential targets for novel antibiotics, as a molecule with the capacity to artificially induce toxin activation could have an antibacterial effect. Described herein is the investigation of the Staphylococcus aureus YefM-YoeBSa1 and YefM-YoeBSa2 TA systems as targets for this artificial activation strategy. Following establishment of the prevalence, conservation, and transcription of the yefM-yoeBSa1 and yefM-yoeBSa2 genes in clinical isolates of methicillin-resistant S. aureus, a peptide activator of the YefM-YoeBSa1 TA system was sought by screening phage-displayed peptide libraries against the YefMSa1 antitoxin. Additionally, a novel strategy was devised to express the YoeBSa1 toxin in an inactive, non-toxic form. Characterization of the activity of YoeBSa1 led to the design of a fluorogenic substrate that can be used to screen for activators of this toxin in a high-throughput manner.

Graduation Semester

2013-05

Permalink

http://hdl.handle.net/2142/44445

Copyright and License Information

Copyright 2013 Amy Susanne Larson

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