Abstract

As reported by the CDC in 2019, 35,000 Americans die each year from antibiotic resistant infections. There are on average 2.8 million drug-resistant infections in the US annually, and it is projected that by 2050, 10 million lives each year will be at risk of fatal infections from resistant microbes if the current trends continue. In addition to the rise of drug resistant bacteria, there has also been a steady decline in novel antibiotics developed to treat these increasingly resistant bacteria. Two main approaches to this issue are the isolation of antibiotic compounds with novel mechanisms of action against infectious bacteria and the identification of adjuvant compounds that can decrease the efficiency of resistance mechanisms. Many of the currently marketed antibiotics were discovered through isolation of easily cultured single-culture bacteria. However, since the environment of the laboratory does not reflect the natural environment for most bacteria, thousands of biosynthetic genes that may lead to antibiotics remain silent when cultured under these conditions. By creating a more natural competitive environment representative of the diversity of bacteria in soil, co-cultures of two or more bacteria can stimulate these biosynthetically silent genes and yield antibiotic production from bacteria. This work details the isolation of potentially novel antibiotics produced by cocultured rhizosphere soil bacteria. With two different co-cultures, the potentially novel antibiotic compounds produced by these bacteria have been extracted and isolated using liquid-liquid extractions, solid-phase extractions, and flash chromatography. The compound from one of the co-cultures began characterization using 1H- Nuclear Magnetic Resonance (NMR) and 13C-NMR data. To address the second approach to combating antibiotic resistant bacteria, several compounds in the Wolfe Laboratory’s compound library were tested for general adjuvant activity with a panel of bacteria and antibiotics. Additionally, several compounds were tested in a biofilm assay against Pseudomonas aeruginosa.

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