Graduate Thesis Or Dissertation
 

Evaluation of peptide phosphorodiamidate morpholino oligomers as a novel antibiotic therapy

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https://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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