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Lett Appl Microbiol. 2009 Jul;49(1):8-13. doi: 10.1111/j.1472-765X.2009.02582.x. Epub 2009 May 15.

Screening method to identify inhibitors of siderophore biosynthesis in the opportunistic fungal pathogen, Aspergillus fumigatus.

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1
Department of Biological Sciences, Simon Fraser University, Burnaby BC, Canada.

Abstract

AIMS:

Aspergillus fumigatus is the most common cause of airborne mould infections in immunocompromised patients worldwide. Our aim was to develop a method to identify agents that inhibit siderophore biosynthesis because this pathway is unique to the fungus and is essential for virulence.

METHODS AND RESULTS:

A high-throughput two-step screening assay was developed using 96-well plates in which fungal growth and siderophore production is assessed spectrophotometrically. If a compound inhibits growth only in iron-limited medium (screen 1), its effect on siderophore production is then determined (screen 2). The proof of concept was demonstrated using a known antifungal agent, amphotericin B, and a strain of A. fumigatus deficient in siderophore production.

CONCLUSIONS:

The two-stage screening method clearly identified growth defects in A. fumigatus related specifically to siderophore biosynthesis.

SIGNIFICANCE AND IMPACT OF THE STUDY:

The increasing incidence of life-threatening fungal infections has produced an urgent need for novel antifungal agents. The method described in this report will facilitate the identification of novel antifungal compounds that inhibit a pathway critical for A. fumigatus virulence and have a reduced probability of affecting host metabolism.

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