Abstract Title

Analysis of Extracellular Metabolites in MTN deficient E. coli Strains Illuminates Potential Antibiotic Mechanisms

Disciplines

Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Microbial Physiology

Abstract

The emergence of increasing rates of antibiotic resistance requires that new antibiotics be developed that work through novel mechanisms of action. One potential bacterial target is the enzyme is methylthioadenosine/S-adenosylhomocysteine nuclosidase (MTN), which salvages adenine and methionine used in S-adenosylmethionine (SAM) dependent reactions, and plays an important role in bacterial virulence. In this study, we examined the effect of MTN deficiency on central carbon metabolism in Escherichia coli to better understand the how MTN inhibitors will work as antibiotics. Metabolites present in cell culture supernatants of a wild-type (WT) and MTN gene knockout (KO) of the E. coli RK4353 strain were quantified by enzyme linked immunosorbent assay (ELISA). Initial data for metabolites including pyruvate, acetate, ethanol, and lactate indicate that MTN KO strains accumulate pyruvate. This suggests that central carbon metabolism will be impaired by drugs that inhibit MTN activity by interruption of radical SAM reactions important for vitamin synthesis, and that this is one mechanism of action by which these antibiotics will function.

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Analysis of Extracellular Metabolites in MTN deficient E. coli Strains Illuminates Potential Antibiotic Mechanisms

The emergence of increasing rates of antibiotic resistance requires that new antibiotics be developed that work through novel mechanisms of action. One potential bacterial target is the enzyme is methylthioadenosine/S-adenosylhomocysteine nuclosidase (MTN), which salvages adenine and methionine used in S-adenosylmethionine (SAM) dependent reactions, and plays an important role in bacterial virulence. In this study, we examined the effect of MTN deficiency on central carbon metabolism in Escherichia coli to better understand the how MTN inhibitors will work as antibiotics. Metabolites present in cell culture supernatants of a wild-type (WT) and MTN gene knockout (KO) of the E. coli RK4353 strain were quantified by enzyme linked immunosorbent assay (ELISA). Initial data for metabolites including pyruvate, acetate, ethanol, and lactate indicate that MTN KO strains accumulate pyruvate. This suggests that central carbon metabolism will be impaired by drugs that inhibit MTN activity by interruption of radical SAM reactions important for vitamin synthesis, and that this is one mechanism of action by which these antibiotics will function.