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AssigneeSimon Fraser University
InventorsMargo Moore, Anna Hissen, Nga Wan
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This application relates to the production and characterization of a mutant strain of Aspergillus fumigatus. The application also relates to a method for inhibiting siderophore biosynthesis in Aspergillus fumigatus and an assay for identifying drug candidates or other agents having potential inhibitory activity. The method may comprise, for example, the step of inhibiting an enzyme catalyzing siderophore biosynthesis, such as L-ornithine N5-oxygenase. In one embodiment the siderophore is a hydroxamate siderophore, such as N′N″N′″-triacetylfusarinine C (TAF) or ferricrocin. A method of preventing or treating fungal infections in a patient is also described comprising administering to the patient an agent suitable for inhibiting fungal secretion of siderophores. The method is particularly useful for immunocompromised patients susceptible to fungal infections caused by Aspergillus fumigatus, such as pulmonary aspergillosis. The invention also relates to diagnostic methods for detecting a biomarker indicative of likely A fumigatus infection in vivo, such as serum presence of TAF.
An isolated nucleic acid fragment comprising a hydroxamate siderophore biosynthetic gene from Aspergillus fumigatus.
The nucleic acid fragment of claim 3, wherein the gene comprises the sidA sequence present in Seq. I.D. No. 1 or a sequence homologous thereto.
A fungal cell from Aspergillus fumigatus having a hydroxamate siderophore biosynthetic gene deleted or disrupted.
A mutant strain of Aspergillus fumigatus with the sidA gene deleted or disrupted.
A fungal cell from Aspergillus fumigatus having a hydroxamate siderophore secretion gene deleted or disrupted.
A siderophore-secretion mutant strain of Aspergillus fumigatus.
An assay comprising the step of screening for agents having the ability to inhibit siderophore biosynthesis, siderophore secretion, or siderophore iron-binding capacity in Aspergillus fumigatus.
An assay comprising the step of screening for agents having the ability to inhibit L-ornithine N5-oxygenase.
A method of inhibiting growth of Aspergillus fumigatus comprising inhibiting siderophore biosynthesis, siderophore secretion or siderophore iron-binding capacity.
A method of preventing or treating fungal infections in a patient comprising administering to the patient an agent suitable for inhibiting fungal secretion of siderophores.
A method of diagnosing Aspergillus fumigatus infection in a subject comprising detecting the presence of a biomarker associated with said infection in serum of the subject.
Dependencies are inferred from the claim text.