Network Medicine

Blueprint for antimicrobial hit discovery targeting metabolic networks

Proceedings of the National Academy of Sciences of the United States of America 10.1073, 1-6 (2010) Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.


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J. Candia, M. C. Gonzalez, P. Wang, T. Schoenharl, G. Madey, A.-L. Barabási

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M. C. Gonzalez, A.-L. Barabási

Nature Physics 3, 224-225 (2007)

K.-I. Goh, M. E. Cusick, D. Valle, B. Childs, M. Vidal, A.-L. Barabási

Proceedings of the National Academy of Sciences 104:21, 8685 (2007)