Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Belenky P,Ye JD,Porter CB,Cohen NR,Lobritz MA,Ferrante T,Jain S,Korry BJ,Schwarz EG,Walker GC,Collins JJ

doi

10.1016/j.celrep.2015.09.059

subject

Has Abstract

pub_date

2015-11-03 00:00:00

pages

968-80

issue

5

issn

2211-1247

pii

S2211-1247(15)01101-8

journal_volume

13

pub_type

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