2010
//
Network Medicine

Blueprint for antimicrobial hit discovery targeting metabolic networks

Abstract
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.

..

More publications
J. Park, D. S. Lee, N. A. Christakis, A.-L. Barabási

Molecular Systems Biology 5:262, 1-7 (2009)

view
J.-P. Onnela, J. Saramäki, J. Hyvönen, G. Szabó, M A. de Menezes, K. Kaski, A.-L. Barabási, J. Kertész

New Journal of Physics 9, 1-27 (2007)

view
M. C. Gonzalez, A.-L. Barabási

Nature Physics 3, 224-225 (2007)

view