(535f) Efflux and Metabolism: Elucidating the Mechanisms of Metabolite Overflow and Secretion

Bacteria such as Escherichia coli have evolved a complex repertoire of mechanisms for limiting the uptake of toxic compounds from their environment. These include altering the structure of the outer membrane, expressing efflux transporters, and redirecting metabolic flux. While these mechanisms have traditionally been implicated in intrinsic antibiotic resistance, we have recently shown that they also limit the accumulation of metabolic intermediates. For example, 4-hydroxybenzoate, 2,3-dihydroxybenzoate and anthranilate, involved in ubiquinone, enterobactin and tryptophan biosynthesis, respectively, induce the same resistance and tolerance mechanisms as do antibiotics such as salicylic acid. In addition, we have identified a number of efflux transporters that secrete sugars from the cell. These results suggest that many of the antibiotic resistance mechanisms intrinsic to bacteria are also utilized to prevent the accumulation of toxic metabolites and potentially to function as relief valves for metabolite overflow.

In this work, we will discuss our ongoing efforts to elucidate the mechanisms of intrinsic antibiotic resistance in E. coli and its role in metabolism. We will also discuss how these finding may yield new approaches and targets for metabolic engineering.