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To verify antifungal chemosensitizing agents discovered in in vitro bioassays are also functional in a mammalian animal model system using BALB/c mice.
Approach:
Chemosensitizing agents will be determined by PMR scientists using standard in vitro (Petri dish, microtitre plate) bioassays. These assays will include commercial antifungal agents co-applied with candidate chemosensitizing agents. A number of fungi pathogenic to animals and humans will be included such as Aspergillus flavus, A. fumigatus, A. terreus and Candida species and Cryptococcus neoformans. Agents found to be effective under in vitro assays will be provided to a collaborator at Montana State University. Animal testing will use neutropenic mice, BALB/c. The mice are treated with cyclophosphamide i. p. prior to infection, then with antifungal drug and chemosensitizing agent. The mice will be infected, nasally. The following day, treatments will be administered in five cohorts, a Tween control, one receiving only fungi, one receiving only antifungal drug, one receiving only chemosensitizing agent and one will receive both antifungal drug and chemosensitizer.