{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/44445"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/44445","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Investigation of the YefM-YoeBSa toxin-antitoxin systems as novel antibacterial targets","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Larson, Amy"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Hergenrother, Paul J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-05-24T22:16:25Z","date_published":"2013-05-24T22:16:25Z","updated_at":"2026-07-22T22:25:34Z","subjects":["toxin-antitoxin system","antibacterial"],"languages":["en"],"rights":["Copyright 2013 Amy Susanne Larson"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/44445","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hergenrother, Paul J."]},{"key":"dc:creator","label":"Author","values":["Larson, Amy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-05-24T22:16:25Z","2015-05-24T10:01:42Z","2013-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["toxin-antitoxin system","antibacterial"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2013 Amy Susanne Larson"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/44445"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-04-22T15:37:24Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Larson_Amy.docx: 5124480 bytes, checksum: 4df59701a40f872b27b042d9b6da0aa0 (MD5) Larson_Amy.pdf: 3212970 bytes, checksum: ff9f72f2f0c3c5aca7d4f8e20edd66c3 (MD5)","Made available in DSpace on 2013-05-24T22:16:25Z (GMT). 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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.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-04-22T15:37:24Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Larson_Amy.docx: 5124480 bytes, checksum: 4df59701a40f872b27b042d9b6da0aa0 (MD5) Larson_Amy.pdf: 3212970 bytes, checksum: ff9f72f2f0c3c5aca7d4f8e20edd66c3 (MD5)","Made available in DSpace on 2013-05-24T22:16:25Z (GMT). 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