Honors College Thesis
 

Antisense Antibiotics

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https://ir.library.oregonstate.edu/concern/honors_college_theses/70795946j

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  • Two different types of Phosphorodiamidate Morpholino Oligomers (PMOs) were used to inhibit growth in pure cultures of Salmonella enterica serovar typhimurium and in mouse macrophages infected with S. typhimurium. Both PMOs were 11 bases long and complementary to bases 6-16 of acyl carrier protein mRNA. A membrane-penetrating peptide, (RXR)4XB, was attached to the 3’ end of both PMOs (R is arginine, X is 6- aminohexanoic acid, and B is β-alanine). One PMO (AcpP) had the standard neutral linkages while the other (Pip-AcpP) was modified with three cationic piperazines interspersed between the linkages. Scrambled sequence controls of both types of PMOs were synthesized (Scr, Pip-Scr). The minimal inhibitory concentrations (MIC) of the AcpP, Pip-AcpP, Scr, and Pip-Scr were 1.25 μM, 0.156 μM, >160 μM, and >160 μM respectively. The growth curve assay showed that Pip-AcpP significantly inhibited growth at 2.5 μM as compared to an untreated control. There was no inhibition for AcpP, Scr, or Pip-Scr at the same concentration. The tissue culture assay showed that Pip-AcpP reduced the viability of S. typhimurium growing intracellularly in mouse macrophages by 5 to 6 orders of magnitude over 48 hours. The Pip-Scr showed no inhibition over the same period. In conclusion, the Pip-AcpP proved to more effective than AcpP in pure culture and was able to significantly reduce bacterial growth in tissue culture as well.
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