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

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.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Larson, Amy

Contributors dc:contributor

• Hergenrother, Paul J.

• toxin-antitoxin system
• antibacterial

Statement dc:rights

• Copyright 2013 Amy Susanne Larson

Language dc:language

en

Handle dc:identifier

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

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/44445