title: In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans.
abstract: Several azoles are widely used to treat human fungal infections. Increasing resistance to these azoles has prompted exploration of their synergistic antifungal activities when combined with other agents. The amphiphilic aminoglycoside, K20, was recently shown to inhibit filamentous fungi, yeasts and heterokonts, but not bacteria. In this study, in vitro synergistic growth inhibition by combinations of K20 and azoles (fluconazole, itraconazole, voriconazole, clotrimazole, or posaconazole) were examined against Candida species and Cryptococcus neoformans. Checkerboard microbroth dilution, time-kill curve, and disk diffusion assays revealed that K20 has synergistic inhibitory activities with all five azoles against C. albicans including azole-resistant C. albicans strains ATCC 64124 and ATCC 10231. Four (fluconazole, itraconazole, clotrimazole, posaconazole) and three (fluconazole, itraconazole, voriconazole) azoles were synergistically inhibitory with K20 against C. lusitaniae and C. tropicalis, respectively. Only posaconazole showed synergy with K20 against two Cryptococcus neoformans strains (90-26 and VR-54). Time-kill curves with azole-resistant C. albicans 64124 and azole-sensitive C. albicans MYA-2876 confirmed the K20-azole synergistic interactions with a ≥ 2 log10 decrease in colony-forming units (CFU)/ml compared with the corresponding azoles alone. These results suggest that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis.
authors.affiliation: Department of Biology, Utah State University, Logan, Utah, USA Synthetic Bioproducts Center, Utah State University, North Logan, Utah, USA.
authors.forename: Sanjib K
authors.initials: SK
authors.lastname: Shrestha
authors.affiliation: Department of Biology, Utah State University, Logan, Utah, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Grilley
authors.affiliation: Department of Biology, Utah State University, Logan, Utah, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Anderson
authors.affiliation: Department of Biology, Utah State University, Logan, Utah, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Dhiman
authors.affiliation: Synthetic Bioproducts Center, Utah State University, North Logan, Utah, USA.
authors.forename: John
authors.initials: J
authors.lastname: Oblad
authors.affiliation: Synthetic Bioproducts Center, Utah State University, North Logan, Utah, USA Department of Chemistry and Biochemistry, Utah State University, Logan, Utah, USA.
authors.forename: Cheng-Wei T
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biology, Snow College, Ephraim, Utah, USA.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sorensen
authors.affiliation: Department of Biology, Utah State University, Logan, Utah, USA Synthetic Bioproducts Center, Utah State University, North Logan, Utah, USA jon.takemoto@usu.edu.
authors.forename: Jon Y
authors.initials: JY
authors.lastname: Takemoto
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; D001393:Azoles
keywords: Candida; Cryptococcus neoformans; K20; antifungal; azole; synergy