Evaluation of peptide phosphorodiamidate morpholino oligomers as a novel antibiotic therapy Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/kp78gj75k

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  • Peptide-phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind and silence gene targets. Through designing PPMOs that silence essential or resistance genes in pathogens, these antisense oligomers could be utilized as novel antimicrobials. Towards this end, my thesis employed minimum inhibitory concentration assays (MICs) to identify PPMOs capable of inhibiting in vitro growth of E. coli. Quantitative real-time PCR was then used to elucidate PPMO mechanism through investigating transcriptional effects of PPMO treatment. Lastly, tissue culture cytotoxicity tests were performed to ensure PPMO were benign for human cells. My thesis has identified multiple PPMOs capable of silencing the essential gene acpP and the resistance gene NDM-1, establishing a foundation for both independent and combination PPMO antibiotic treatments. My work has also shown PPMO treatment to not significantly affect transcription of target genes, suggesting PPMOs to exert their effects entirely through translational regulation. Finally, the tissue culture assays demonstrates PPMOs to be nontoxic to human cells. Taken together, these data indicate PPMOs are a safe, adaptable, and effective new option for antibiotic therapy.
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  • description.provenance : Submitted by Margo Kaller (kallerm@onid.orst.edu) on 2014-06-06T19:55:17Z No. of bitstreams: 1 KallerMargoO2014.pdf: 3363105 bytes, checksum: 0a48c37bdf01190986ca87d29722fee4 (MD5)
  • description.provenance : Rejected by Julie Kurtz(julie.kurtz@oregonstate.edu), reason: Rejecting for reasons listed - 1) Change the commencement date on the bottom of the title page to read - Commencement June 2014 2) Approval page remove the names, except yours, but remove your middle initial so your name appears exactly the same through your thesis. The signatures lines should read - Major Professor, representing Microbiology Chair of the Department of Microbiology Dean of the Graduate School 3) The actual thesis doesn't have page numbers. 4) The thesis looks like it's in track change mode with lots of words red and underlined. Once revised, log back into ScholarsArchive and go to the upload page. Replace the attached file with the revised file and resubmit. Thanks, Julie on 2014-06-20T21:38:03Z (GMT)
  • description.provenance : Approved for entry into archive by Laura Wilson(laura.wilson@oregonstate.edu) on 2014-07-15T23:10:16Z (GMT) No. of bitstreams: 1 Margo Kaller OSU Thesis for Archives.pdf: 3338233 bytes, checksum: 1daf2d0c34a8fa821e88ebb1adc695e1 (MD5)
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2014-06-26T16:13:15Z (GMT) No. of bitstreams: 1 Margo Kaller OSU Thesis for Archives.pdf: 3338233 bytes, checksum: 1daf2d0c34a8fa821e88ebb1adc695e1 (MD5)
  • description.provenance : Made available in DSpace on 2014-07-15T23:10:16Z (GMT). No. of bitstreams: 1 Margo Kaller OSU Thesis for Archives.pdf: 3338233 bytes, checksum: 1daf2d0c34a8fa821e88ebb1adc695e1 (MD5) Previous issue date: 2014-05-22
  • description.provenance : Submitted by Margo Kaller (kallerm@onid.orst.edu) on 2014-06-26T15:39:50Z No. of bitstreams: 1 Margo Kaller OSU Thesis for Archives.pdf: 3338233 bytes, checksum: 1daf2d0c34a8fa821e88ebb1adc695e1 (MD5)

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