Fig. 3.

Pharmacological inhibition of Hsp90 enhances the efficacy of CS both in vitro and in the Galleria mellonella host-model system. (A) Hsp90 inhibition reduces CS resistance of an A. fumigatus clinical isolate on defined RPMI medium. Antifungal test strips (Etest, AB Biodisk) produce a gradient of drug concentration with the highest at the top. Plates contained vehicle control (DMSO), GdA, or 17-AAG, as indicated. (B) The Hsp90 inhibitor GdA exerts therapeutic benefits in combination with CS in the G. mellonella model of A. fumigatus pathogenesis. Sixteen G. mellonella larvae per treatment group were infected with 10⁷ conidia of a clinical isolate. Larvae were treated with GdA (100 mg/kg) or with CS (1.5 mg/kg) once immediately after infection, as indicated, and were scored daily. (C) A. fumigatus conidia germinate into hyphae during infection of G. mellonella. Tissue sections were taken 24 h after infection, silver stained to identify the fungus, and examined at 100× magnification using a Zeiss Axiovert microscope. (Scale bar, 10 μm.)