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Screening method to identify inhibitors of siderophore biosynthesis in the opportunistic fungal pathogen, Aspergillus fumigatus
Author(s) -
Pinto L.J.,
Moore M.M.
Publication year - 2009
Publication title -
letters in applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.698
H-Index - 110
eISSN - 1472-765X
pISSN - 0266-8254
DOI - 10.1111/j.1472-765x.2009.02582.x
Subject(s) - aspergillus fumigatus , library science , pathogen , biological sciences , clinical microbiology , biology , microbiology and biotechnology , human pathogen , fungal pathogen , computational biology , computer science , gene , genetics
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.