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oai:www.ideals.illinois.edu:2142/17030 2023-07-10 col_2142_5131 col_2142_16338 com_2142_5130 com_2142_16337 com_2142_14793 com_2142_8903

Vancomycin-resistant enterococci (VRE) Methicillin-resistant Staphylococcus aureus (MRSA) relBE Hergenrother, Paul J. Hergenrother, Paul J. Slauch, James M. Wilson, Brenda A. Farrand, Stephen K. Moritz, Elizabeth M. 2010-08-31T20:29:51Z 2010-08-31T20:29:51Z 2012-09-07T16:43:37Z 2010-08-31T20:29:51Z 2010-08 Large, low copy number plasmids, such as those harboring antibiotic resistance genes, often possess plasmid maintenance systems to ensure their persistence and inheritance in a bacterial population. One example is the proteic toxin-antitoxin (TA) system, consisting of a toxin and an antitoxin encoded in a single operon. When expressed, the antitoxin binds to and neutralizes the toxin. However, if during cell division a plasmid-free daughter cell arises, the labile antitoxin is rapidly degraded, freeing the toxin to kill the cell. If TA systems are prevalent and functional in clinically relevant bacteria, they could be exploited as a novel antimicrobial strategy: a small molecule capable of relieving the neutralizing effect of the antitoxin would free the toxin to kill the cell. This thesis research has, in part, focused on defining the prevalence of TA systems in clinical isolates of vancomycin-resistant enterococci and methicillin-resistant S. aureus to validate TA systems as an antibacterial target. Two TA systems, Axe-Txe and RelBE, were found to be common among the pathogenic bacteria surveyed and were therefore further investigated. A cell-based high-throughput assay was developed to screen for small molecules that induce toxin-dependent cell death in E. coli expressing RelBE. Additionally, mechanistic studies were performed to determine the mode of action by which the Txe toxin causes cell death. Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2010-06-17T14:50:19Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Moritz_Elizabeth.pdf: 9591961 bytes, checksum: 7e1c4f5e95fa88b4cc2200184128c603 (MD5) Made available in DSpace on 2010-08-31T20:29:51Z (GMT). No. of bitstreams: 2 Moritz_Elizabeth.pdf: 9591961 bytes, checksum: 7e1c4f5e95fa88b4cc2200184128c603 (MD5) license.txt: 4066 bytes, checksum: b6a45b37517a2d16fc7edf6de6aa5324 (MD5) Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2010-08-31T20:32:51Z Item is restricted until 2012-08-31T20:32:49Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2012-09-07T16:43:37Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations - Microbiology (ID: 748) No. of bitstreams: 3 Moritz_Elizabeth.pdf: 9591961 bytes, checksum: 7e1c4f5e95fa88b4cc2200184128c603 (MD5) license.txt: 4066 bytes, checksum: b6a45b37517a2d16fc7edf6de6aa5324 (MD5) Moritz_Elizabeth.pdf.txt: 593319 bytes, checksum: 19829e614f79c451fcd7368845f60b7d (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2012-09-07T16:43:37Z http://hdl.handle.net/2142/17030 en Copyright 2010 Elizabeth Margaret Moritz toxin-antitoxin Axe-Txe The prevalence of toxin-antitoxin systems and their tractability as novel antimicrobial targets Microbiology 1948 Microbiology 0322 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Microbiology -UIUC 10KS0322PHD