The Antifungal and Synergistic Effect of Bisphosphonates in <i>Cryptococcus</i>
Aidan Kane, Leona T. Campbell, Diana Ky, David E. Hibbs, Dee Carter
Abstract
biofilms, prevented the development of fluconazole resistance, and resolved infection in a nematode model. Supplementation with squalene eliminated bisphosphonate-mediated synergy, demonstrating that synergy was due to the inhibition of squalene biosynthesis. This study demonstrates the utility of targeting squalene synthesis for improving the efficacy of azole-based antifungal drugs and suggests bisphosphonates are promising lead compounds for further antifungal development.
Topics & Concepts
FluconazoleSqualeneCryptococcosisCryptococcusSqualene monooxygenaseEnzymeMicrobiologyBiologyCryptococcus neoformansAntifungalTerbinafineMetabolic pathwayBiosynthesisPharmacologyBiochemistryChemistryItraconazoleFungal Infections and StudiesAntifungal resistance and susceptibilityPeptidase Inhibition and Analysis