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  • 1
    Publikationsdatum: 2016-01-24
    Beschreibung: Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid’s components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance ( mar ) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance.
    Print ISSN: 0737-4038
    Digitale ISSN: 1537-1719
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-02
    Beschreibung: Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baym, Michael -- Stone, Laura K -- Kishony, Roy -- R01-GM081617/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):aad3292. doi: 10.1126/science.aad3292.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA, USA. ; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Department of Biology and Department of Computer Science, Technion - Israel Institute of Technology, Haifa, Israel. rkishony@technion.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26722002" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/*genetics ; Drug Resistance, Bacterial/*genetics ; *Evolution, Molecular ; Humans ; Mutation ; Selection, Genetic
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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