M Gowri1, B Jayashree2, J Jeyakanthan2, E K Girija1. 1. Department of Physics, Periyar University, Salem, Tamil Nadu, India. 2. Department of Bioinformatics, Alagappa University, Karaikudi, India.
Abstract
AIM: The aim of this present study was to investigate the antifungal mechanism of sertraline against Candida auris (C. auris) and its effect on biofilm formation. METHODS AND RESULTS: Sertraline, a repurposing drug with a history of human use for the treatment of depression was screened against three different isolates of C. auris, and was found to possess efficient antifungal activity. The antifungal activity of sertraline was further confirmed by killing kinetics assay and post-antifungal effect (PAFE). Sertraline inhibited C. auris yeast to hyphae conversion and further the inhibition of biofilm formation showed 71% inhibition upon treatment. Cell damage caused due to C. auris after treatment with sertraline was observed using SEM and cell membrane damage was ascertained using flow cytometry by Propidium Iodide (PI) uptake assay. The results of sorbitol protection assay and ergosterol effect assay suggested that sertraline did not affect the cell wall and did not act by binding to membrane ergosterol. The mechanism of action of sertraline against C. auris was understood through in silico docking studies that revealed the binding nature of sertraline to the sterol 14 alpha demethylase which is involved in ergosterol biosynthesis. Ergosterol that was quantified from treated cells showed a 5·5-fold decrease in ergosterol production. CONCLUSION: Sertraline displayed promising antifungal activity against C. auris involved in candidiasis infection and the mechanism of action was predicted. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results of this study can encourage for the development of new antifungal agents and can be promising antifungal agent against C. auris infection.
AIM: The aim of this present study was to investigate the antifungal mechanism of sertraline against Candida auris (C. auris) and its effect on biofilm formation. METHODS AND RESULTS: Sertraline, a repurposing drug with a history of human use for the treatment of depression was screened against three different isolates of C. auris, and was found to possess efficient antifungal activity. The antifungal activity of sertraline was further confirmed by killing kinetics assay and post-antifungal effect (PAFE). Sertraline inhibited C. auris yeast to hyphae conversion and further the inhibition of biofilm formation showed 71% inhibition upon treatment. Cell damage caused due to C. auris after treatment with sertraline was observed using SEM and cell membrane damage was ascertained using flow cytometry by Propidium Iodide (PI) uptake assay. The results of sorbitol protection assay and ergosterol effect assay suggested that sertraline did not affect the cell wall and did not act by binding to membrane ergosterol. The mechanism of action of sertraline against C. auris was understood through in silico docking studies that revealed the binding nature of sertraline to the sterol 14 alpha demethylase which is involved in ergosterol biosynthesis. Ergosterol that was quantified from treated cells showed a 5·5-fold decrease in ergosterol production. CONCLUSION: Sertraline displayed promising antifungal activity against C. auris involved in candidiasis infection and the mechanism of action was predicted. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results of this study can encourage for the development of new antifungal agents and can be promising antifungal agent against C. auris infection.
Authors: Jamie L Dombach; Joaquin L J Quintana; Toni A Nagy; Chun Wan; Amy L Crooks; Haijia Yu; Chih-Chia Su; Edward W Yu; Jingshi Shen; Corrella S Detweiler Journal: PLoS Pathog Date: 2020-12-08 Impact factor: 6.823