Abstract:
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Zampieri M,Zimmermann M,Claassen M,Sauer Udoi
10.1016/j.celrep.2017.04.002subject
Has Abstractpub_date
2017-05-09 00:00:00pages
1214-1228issue
6issn
2211-1247pii
S2211-1247(17)30461-8journal_volume
19pub_type
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