Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase
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- Maya A. Farha
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;
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- Tomasz L. Czarny
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;
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- Cullen L. Myers
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;
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- Liam J. Worrall
- Department of Biochemistry and Molecular Biology and the Center for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;
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- Shawn French
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;
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- Deborah G. Conrady
- Department of Biochemistry and Molecular Biology and the Center for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;
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- Yang Wang
- Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, IL 61801
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- Eric Oldfield
- Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, IL 61801
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- Natalie C. J. Strynadka
- Department of Biochemistry and Molecular Biology and the Center for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;
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- Eric D. Brown
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;
書誌事項
- 公開日
- 2015-08-17
- DOI
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- 10.1073/pnas.1511751112
- 公開者
- National Academy of Sciences
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説明
<jats:title>Significance</jats:title> <jats:p>Small molecule probes have proved indispensable in dissecting bacterial systems. Their combinations have further expanded their utility as tools by enabling the study of interacting pathways. As such, screens for synergy between compounds have been widely used to reveal functional connections among cellular components. The utility of antagonism, however, has largely been overlooked. This study highlights the value of antagonistic interactions in elucidating genetic networks and mechanisms of drug action. Herein, we report on the discovery of clomiphene, an inhibitor of bacterial cell wall synthesis, uncovered through a systematic screen for antagonism. The discovery of clomiphene shed light on the pathways of cell wall biogenesis and, importantly, represents a new promising lead for the fight against infection.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (35), 11048-11053, 2015-08-17
National Academy of Sciences
