Abstract

Increasing bacterial resistance to current antibiotic treatments poses a huge threat to the health of the human population. Over the past 20 years, there has been a significant decline in the production of new antibiotics, despite the rapid emergence of drug resistant pathogens. The isolation and extraction of structurally unique antibiotics from bacteria remains largely uninvestigated by current researchers. Natural products, however, are an abundant source of structurally diverse compounds with antibacterial activity that can be used to develop new and potent antibiotics. This research investigates techniques for determining optimal growth media and optimal time of antibiotic production for each bacteria sample from a library of bacteria species, as well as the extraction of antibiotic active compounds from bacteria. In addition, this research also explores the isolation and extraction of the compound pseudopyronine B, from a Pseudomonas species found in garden soil in Western North Carolina, and SAR evaluation of C3 and C6 alkyl analogs of the natural product for antibacterial activity against Gram-positive and Gram-negative bacteria. A direct relationship between antibacterial activity and C3/C6 alkyl chain length was observed. For inhibition of Gram-positive bacteria, alkyl chain lengths between 6-8 carbons were found to be the most active (IC50 = 0.04-3.8 μg/mL) and short alkyl chain analogs showed modest activity against Gram-negative bacteria (IC50 = 222-303 μg/mL).

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