Investigation of the Antibiotic Detoxification Response of Escherichia coli cells Toward Fosmidomycin via Differential Proteomics

摘要

Antibiotics are the primary means used to combat infections, however, modern medicine is faced with a fundamental dilemma: treating bacteria with antibiotics provides a selective pressure on the organism to evolve ways to resist the antibiotic in order to survive.1 The metabolic response of bacteria exposed to antibiotics can provide clues into the mechanism the organism may use to overcome these treatments. Fosmidomycin is an inhibitor of the methylerythritol phosphate (MEP) pathway, which is a recently elucidated requisite pathway in both Gram-positive and Gram-negative species.The MEP pathway is the only means many bacteria have to make isoprenoid compounds, which are used by bacteria to make numerous metabolites involved in cellular respiration and division, and inhibition of this pathway is lethal to the organism. The MEP pathway is found in all category A and B biothreat agents, as well as those responsible for numerous prevalent nocosomial infections. However, no homologous proteins exist in humans or animals, so inhibitors of these proteins are attractive as broad-scale antibiotics. Currently, much research is underway to develop novel MEP pathway inhibitors as a new family of antibiotic compounds.