Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage
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Belenky-2015-Bactericidal Antibio.pdf
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Author(s)
Belenky, Peter
Ye, Jonathan D.
Cohen, Nadia R.
Ferrante, Thomas
Jain, Saloni
Korry, Benjamin J.
Schwarz, Eric G.
Walker, Graham C.
Collins, James J.
Porter, Caroline
Date Issued
October 2015
Journal
Cell Reports
Publisher
Elsevier
Citation
Belenky, Peter, Jonathan D. Ye, Caroline B.M. Porter, Nadia R. Cohen, Michael A. Lobritz, Thomas Ferrante, Saloni Jain, et al. “Bactericidal Antibiotics Induce Toxic Metabolic Perturbations That Lead to Cellular Damage.” Cell Reports 13, no. 5 (November 2015): 968–980.
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Final published version
Abstract
Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones). These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.
MIT Department
Institute for Medical Engineering and Science
MIT Synthetic Biology Center
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.09.059
