A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

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A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

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Title: A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity
Author: Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared D'Alonzo; Lambert, Kathleen G; McAdam, Alexander John; Husson, Robert N; Clardy, Jon C.; Tamayo, Giselle; Watnick, Paula Ivonne

Note: Order does not necessarily reflect citation order of authors.

Citation: Ymele-Leki, Patrick, Shugeng Cao, Jared Sharp, Kathleen G. Lambert, Alexander J. McAdam, Robert N. Husson, Giselle Tamayo, Jon Clardy, and Paula I. Watnick. 2012. A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS ONE 7(2): e31307.
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Abstract: Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against \(Escherichia\) \(coli\), \(Pseudomonas\) \(aeruginosa\), \(Vibrio\) \(cholerae\), methicillin-resistant \(Staphylococcus\) \(aureus\), and \(Mycobacterium\) \(tuberculosis\). This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples.
Published Version: doi:10.1371/journal.pone.0031307
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281070/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9361515

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