a high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity高通量屏幕识别新的和广谱抗菌活性天然产物.pdfVIP

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a high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity高通量屏幕识别新的和广谱抗菌活性天然产物.pdf

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a high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity高通量屏幕识别新的和广谱抗菌活性天然产物

A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity 1 2 1 3 3 Patrick Ymele-Leki , Shugeng Cao , Jared Sharp , Kathleen G. Lambert , Alexander J. McAdam , 1 4 2 1 Robert N. Husson , Giselle Tamayo , Jon Clardy , Paula I. Watnick * 1 Division of Infectious Diseases, Children’s Hospital, Boston, Boston, Massachusetts, United States of America, 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, United States of America, 3 Department of Laboratory Medicine, Children’s Hospital, Boston, Boston, Massachusetts, United States of America, 4 Unidad Estrategica de Bioprospeccion, Instituto Nacional de Biodiversidad (INBio) and Escuela de ´ ´ Quımica, Universidad de Costa Rica, San Jose, Costa Rica 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