| Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. | |
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MedLine Citation:
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PMID: 23292609 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS), we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria's susceptibility to oxidative attack. We developed an ensemble approach of genome-scale, metabolic models capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. Targets that were predicted in silico were experimentally validated and further shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics. |
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Authors:
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Mark P Brynildsen; Jonathan A Winkler; Catherine S Spina; I Cody Macdonald; James J Collins |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-06 |
Journal Detail:
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Title: Nature biotechnology Volume: - ISSN: 1546-1696 ISO Abbreviation: Nat. Biotechnol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9604648 Medline TA: Nat Biotechnol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Howard Hughes Medical Institute, Department of Biomedical Engineering, and Center for BioDynamics, Boston University, Boston, Massachusetts, USA. [2] Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA. [3]. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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