A High-throughput Screen Identifies a New Natural Product with Broad-spectrum Antibacterial Activity

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 24

PMID 22359585

Citations 19

Authors

Patrick Ymele-Leki

Shugeng Cao

Jared Sharp

Kathleen G Lambert

Alexander J McAdam

Robert N Husson

Giselle Tamayo

Jon Clardy

Paula I Watnick

Affiliations

Soon will be listed here.

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.

Citing Articles

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.

Ayon N Metabolites. 2023; 13(5).

PMID: 37233666 PMC: 10220967. DOI: 10.3390/metabo13050625.

Antibacterial, Antibiofilm, and Antioxidant Activity of 15 Different Plant-Based Natural Compounds in Comparison with Ciprofloxacin and Gentamicin.

Pormohammad A, Hansen D, Turner R Antibiotics (Basel). 2022; 11(8).

PMID: 36009966 PMC: 9404727. DOI: 10.3390/antibiotics11081099.

Phytochemicals: A Promising Weapon in the Arsenal against Antibiotic-Resistant Bacteria.

Khameneh B, Eskin N, Iranshahy M, Bazzaz B Antibiotics (Basel). 2021; 10(9).

PMID: 34572626 PMC: 8472480. DOI: 10.3390/antibiotics10091044.

Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review.

Alvarez-Martinez F, Barrajon-Catalan E, Micol V Biomedicines. 2020; 8(10).

PMID: 33050619 PMC: 7601869. DOI: 10.3390/biomedicines8100405.

A structural analog of ralfuranones and flavipesins promotes biofilm formation by Vibrio cholerae.

Waseem M, Williams J, Thangavel A, Still P, Ymele-Leki P PLoS One. 2019; 14(4):e0215273.

PMID: 30998780 PMC: 6472748. DOI: 10.1371/journal.pone.0215273.

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