Combination of Antifungal Drugs and Protease Inhibitors Prevent Candida albicans Biofilm Formation and Disrupt Mature Biofilms

Frontiers in Microbiology
Matthew B LohseClarissa J Nobile

Abstract

Biofilms formed by the fungal pathogen Candida albicans are resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to prevent C. albicans biofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents for Candida infections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment of C. albicans biofilm infections.

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Citations

Nov 27, 2020·International Journal of Molecular Sciences·Jana TitsKarin Thevissen
Oct 14, 2020·Antimicrobial Agents and Chemotherapy·Hassan E EldesoukyMohamed N Seleem
Dec 31, 2020·Journal of Fungi·Matthew B LohseClarissa J Nobile
Mar 28, 2021·Current Microbiology·Sonam GuptaVikas Pruthi
Apr 13, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Jiří DostálMartin Lepšík
Apr 30, 2021·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Mayram HaciogluAlpcan Kirinti
Aug 7, 2021·Critical Reviews in Microbiology·Maryam RoudbaryCélia F Rodrigues
Oct 5, 2021·Infection and Immunity·Wisely ChuaHao Li

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Methods Mentioned

BETA
Assay
gene knockouts

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