PMID- 28494870
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20201209
IS  - 2211-1247 (Electronic)
VI  - 19
IP  - 6
DP  - 2017 May 9
TI  - Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic 
      Perturbations.
PG  - 1214-1228
LID - S2211-1247(17)30461-8 [pii]
LID - 10.1016/j.celrep.2017.04.002 [doi]
AB  - Microbes have shown a remarkable ability in evading the killing actions of 
      antimicrobial agents, such that treatment of bacterial infections represents once 
      more an urgent global challenge. Understanding the initial bacterial response to 
      antimicrobials may reveal intrinsic tolerance mechanisms to antibiotics and 
      suggest alternative and less conventional therapeutic strategies. Here, we used 
      mass spectrometry-based metabolomics to monitor the immediate metabolic response 
      of Escherichia coli to a variety of antibiotic perturbations. We show that rapid 
      metabolic changes can reflect drug mechanisms of action and reveal the active 
      role of metabolism in mediating the first stress response to antimicrobials. We 
      uncovered a role for ammonium imbalance in aggravating chloramphenicol toxicity 
      and the essential function of deoxythymidine 5'-diphosphate (dTDP)-rhamnose 
      synthesis for the immediate transcriptional upregulation of GyrA in response to 
      quinolone antibiotics. Our results suggest bacterial metabolism as an attractive 
      target to interfere with the early bacterial response to antibiotic treatments 
      and reduce the probability for survival and eventual evolution of antibiotic 
      resistance.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Zampieri, Mattia
AU  - Zampieri M
AD  - Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. 
      Electronic address: zampieri@imsb.biol.ethz.ch.
FAU - Zimmermann, Michael
AU  - Zimmermann M
AD  - Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
FAU - Claassen, Manfred
AU  - Claassen M
AD  - Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
FAU - Sauer, Uwe
AU  - Sauer U
AD  - Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. 
      Electronic address: sauer@imsb.biol.ethz.ch.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Ammonium Compounds)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Nucleoside Diphosphate Sugars)
RN  - 0 (Quinolones)
RN  - 0 (Thymine Nucleotides)
RN  - 2147-59-3 (thymidine diphosphate rhamnose)
RN  - 66974FR9Q1 (Chloramphenicol)
RN  - EC 5.99.1.3 (DNA Gyrase)
SB  - IM
MH  - Ammonium Compounds/metabolism
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Chloramphenicol/*pharmacology
MH  - DNA Gyrase/genetics/metabolism
MH  - Escherichia coli/drug effects/genetics/metabolism
MH  - Escherichia coli Proteins/genetics/metabolism
MH  - Metabolome/*drug effects
MH  - Nucleoside Diphosphate Sugars/metabolism
MH  - Quinolones/*pharmacology
MH  - Thymine Nucleotides/metabolism
OTO - NOTNLM
OT  - E. coli
OT  - ammonium imbalance
OT  - antibiotic response
OT  - antibiotic tolerance
OT  - chloramphenicol
OT  - dTDP-rhamnose
OT  - metabolomics
OT  - quinolones
EDAT- 2017/05/13 06:00
MHDA- 2018/02/23 06:00
CRDT- 2017/05/13 06:00
PHST- 2016/06/09 00:00 [received]
PHST- 2016/09/27 00:00 [revised]
PHST- 2017/03/31 00:00 [accepted]
PHST- 2017/05/13 06:00 [entrez]
PHST- 2017/05/13 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
AID - S2211-1247(17)30461-8 [pii]
AID - 10.1016/j.celrep.2017.04.002 [doi]
PST - ppublish
SO  - Cell Rep. 2017 May 9;19(6):1214-1228. doi: 10.1016/j.celrep.2017.04.002.