Converting an Antibacterial Aminoglycoside into a Fungicide via Simple Chemical Modification. New Strategy for Reviving Old Drugs

Document Type

Article

Journal/Book Title

Journal of Antibiotics

Publication Date

10-6-2010

Publisher

Japan Antibiotics Research Group

Volume

63

First Page

667

Last Page

672

Abstract

Many Actinomycetes aminoglycosides are widely used antibiotics. Although mainly antibacterials, a few known aminoglycosides also inhibit yeasts, protozoans and important crop pathogenic fungal oomycetes. Here we show that attachment of a C8 alkyl chain to ring III of a neamine-based aminoglycoside specifically at the 4″-o position yields a broad-spectrum fungicide (FG08) without the antibacterial properties typical for aminoglycosides. Leaf infection assays and greenhouse studies show that FG08 is capable of suppressing wheat fungal infections by Fusarium graminearum—the causative agent of Fusarium head blight—at concentrations that are minimally phytotoxic. Unlike typical aminoglycoside action of ribosomal protein translation miscoding, FG08's antifungal action involves perturbation of the plasma membrane. This antibacterial to antifungal transformation could pave the way for the development of a new class of aminoglycoside-based fungicides suitable for use in crop disease applications. In addition, this strategy is an example of reviving a clinically obsolete drug by simple chemical modification to yield a new application.

Comments

PubMed PMID: 20924381

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