Antifungal activity of Allyl isothiocyanate by targeting signal transduction pathway, ergosterol biosynthesis, and cell cycle in Candida albicans

Abstract

Background and Purpose: In recent years, the inclusion of Candida albicans on the list of infections that pose a threat due to drug resistance has urged researchers to look into cutting-edge and effective antifungal medications. In this regard, the current study investigated the probable mode of action of allyl isothiocyanate (AITC) against Candida albicans.Materials and Methods: In this study, planktonic assay, germ tube inhibition assay, adhesion, and biofilm formation assay were performed to check the growth and virulence factors. Furthermore, ergosterol assay, reactive oxygen production analysis, cell cycle analysis, and quantitative real-time polymerase chain reaction analysis were performed with the aim of finding the mode of action. A biomedical model organism, like a silkworm, was used in an in vivo study to demonstrate AITC anti-infective ability against C. albicansinfection.Results: Allyl isothiocyanate completely inhibited ergosterol biosynthesis in C. albicans at 0.125 mg/ml. Allyl isothiocyanate produces reactive oxygen species in both planktonic and biofilm cells of C. albicans. At 0.125 mg/ml concentration, AITC arrested cells at the G2/M phase of the cell cycle, which may induce apoptosis in C. albicans. In quantitative real-time polymerase chain reaction analysis, it was found that AITC inhibited virulence factors, like germ tube formation, at 0.125 mg/ml concentration by downregulation of PDE2, CEK1, TEC1 by 2.54-, 1.91-, and 1.04-fold change, respectively, and upregulation of MIG1, NRG1, and TUP1 by 9.22-, 3.35-, and 7.80-fold change, respectively. The in vivo study showed that AITC treatment successfully protected silkworms against C. albicans infections and increased their survival rate by preventing internal colonization by C. albicans.Conclusion: In vitro and in vivo studies revealed that AITC can be an alternative therapeutic option for the treatment of C. albicans infection.

Keywords

• allyl isothiocyanate
• candida albicans
• ergosterol biosynthesis
• rt-pcr
• silkworm