Antimicrobial Inhibitors of the trans-Translation Pathway
As antibiotic resistance becomes an increasing threat to our public health, it is necessary that we take actions to find new bacterial targets and develop new antibiotics. One promising antibacterial target that has not previously been used to clinically develop an antibiotic is the trans-translation pathway. Since many natural products have been found to have antimicrobial properties, natural products are a promising source to turn to in order to find new compounds that inhibit trans-translation. Three plant species were collected from Pennsylvania State University’s Arboretum and were used to prepare crude extracts. The crude extracts were tested for antibacterial properties using minimum inhibitory concentration (MIC) assays and were then purified to yield fractions with many different compounds in them. The fractions were tested using MIC assays and contents from the MIC wells were plated to determine if the compounds have bactericidal and bacteriostatic properties. It was determined that both the crude extracts and the purified fractions contained antimicrobial properties. Additionally, the fractions were tested in a fluorescence-based reporter assay to see if they are trans-translation inhibitors. It was discovered that none of the fractions had any significant inhibition against trans-translation. Overall, this study has utilized natural products to find molecules that inhibit trans-translation and have the potential to become promising new antibiotics. In addition, this thesis discusses a promising class of trans-translation inhibitors are the hydrazine carbonothiols. The mechanism of action of the hydrazine carbonothiols was previously determined to be the ribosomal protein L7/L12. Growth recovery experiments were conducted to validate that the molecular target of the hydrazine carbonothiols is L7/L12. Confirming that the molecular target of the hydrazine carbonothiols has given insight into the mechanism of action of these compounds.
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|Work Title||Antimicrobial Inhibitors of the trans-Translation Pathway|
|License||CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)|
|Publication Date||April 14, 2021|
|Deposited||April 13, 2021|
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