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Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage.
Belenky, Peter; Ye, Jonathan D; Porter, Caroline B M; Cohen, Nadia R; Lobritz, Michael A; Ferrante, Thomas; Jain, Saloni; Korry, Benjamin J; Schwarz, Eric G; Walker, Graham C; Collins, James J.
Afiliación
  • Belenky P; Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, 36 Cummington Mall, Boston, MA 02215, USA; Department of Molecular Microbiology and Immunology, Brown University, 171 Meeting Street, Providence, RI 02912, USA. Electronic address: peter_belenky@brown.edu.
  • Ye JD; Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, 36 Cummington Mall, Boston, MA 02215, USA.
  • Porter CB; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Wyss Institute
  • Cohen NR; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle,
  • Lobritz MA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Wyss Institute
  • Ferrante T; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA.
  • Jain S; Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, 36 Cummington Mall, Boston, MA 02215, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachus
  • Korry BJ; Department of Molecular Microbiology and Immunology, Brown University, 171 Meeting Street, Providence, RI 02912, USA.
  • Schwarz EG; Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, 36 Cummington Mall, Boston, MA 02215, USA.
  • Walker GC; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Collins JJ; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Wyss Institute
Cell Rep ; 13(5): 968-80, 2015 Nov 03.
Article en En | MEDLINE | ID: mdl-26565910
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 (?-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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Kanamicina / Norfloxacino / Estrés Oxidativo / Escherichia coli / Ampicilina / Antibacterianos Idioma: En Revista: Cell Rep Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Kanamicina / Norfloxacino / Estrés Oxidativo / Escherichia coli / Ampicilina / Antibacterianos Idioma: En Revista: Cell Rep Año: 2015 Tipo del documento: Article