A combination approach to treating fungal infections

Sanjib K. Shrestha; Marina Y. Fosso; Sylvie Garneau-Tsodikova

doi:10.1038/srep17070

A combination approach to treating fungal infections

Sanjib K. Shrestha
, Marina Y. Fosso
, Sylvie Garneau-Tsodikova

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C 12 and C 14, were shown to display antifungal activities. Herein, the antifungal synergy of C 12 and C 14 with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains were synergistically inhibited by C 12 when combined with azoles, with the exception of C. albicans 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, C 14 exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC-C 14 and VOR-C 14 showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C 12 /C 14 and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C 12 or C 14 with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency.

Original language	English
Article number	17070
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep17070
State	Published - Nov 23 2015

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.). We thank Drs. Gregory A. Graf and Markos Leggas (University of Kentucky) for letting us use their fluorescence microscope and cell culture facilities, respectively. We also thank Drs. Lisa J. Vaillancourt and Jon S. Thorson (University of Kentucky) as well as Dr. Dr. Jon Y. Takemoto (Utah State University) for providing some of the fungal strains used in our study. This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.).

Funding

This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.). We thank Drs. Gregory A. Graf and Markos Leggas (University of Kentucky) for letting us use their fluorescence microscope and cell culture facilities, respectively. We also thank Drs. Lisa J. Vaillancourt and Jon S. Thorson (University of Kentucky) as well as Dr. Dr. Jon Y. Takemoto (Utah State University) for providing some of the fungal strains used in our study. This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.).

Funders	Funder number
National Institutes of Health (NIH)
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	R01AI090048
University of Kentucky

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title = "A combination approach to treating fungal infections",

abstract = "Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C 12 and C 14, were shown to display antifungal activities. Herein, the antifungal synergy of C 12 and C 14 with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains were synergistically inhibited by C 12 when combined with azoles, with the exception of C. albicans 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, C 14 exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC-C 14 and VOR-C 14 showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C 12 /C 14 and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C 12 or C 14 with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency.",

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note = "Funding Information: This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.). We thank Drs. Gregory A. Graf and Markos Leggas (University of Kentucky) for letting us use their fluorescence microscope and cell culture facilities, respectively. We also thank Drs. Lisa J. Vaillancourt and Jon S. Thorson (University of Kentucky) as well as Dr. Dr. Jon Y. Takemoto (Utah State University) for providing some of the fungal strains used in our study. This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.).",

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ER -

A combination approach to treating fungal infections

Abstract

Bibliographical note

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