Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis

Abstract

This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol.However, CUR alone at its synergistic concentration (lower than MIC 50 ), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in PGLs composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR.Our study first time shows that CUR, for its antifungal activity, targets and down regulates Δ 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of ROS and cell death.

Anti-infective Properties of the Golden Spice Curcumin

“…In general, curcumin exhibits antifungal activity against planktonic forms of standard and at least 10 clinical Candida strains (Neelofar et al, 2011). Sharma et al (2010b, 2012) explained this by curcumin-induced modifications of the fungus membrane lipid composition, which eventually leads to the production of ROS, triggering early apoptosis. Furthermore, Kumar et al (2014) showed that curcumin downregulates cell wall integrity pathway genes, causing cell wall damage and membrane permeabilization in C. albicans .…”

Does Curcumin Have a Role in the Interaction between Gut Microbiota and Schistosoma mansoni in Mice?

“…was also detected by Gow et al [44]; however, this was in vitro. The antifungal CUR effect was explained by its effect on the composition of the lipid membrane that leads to reactive oxygen species (ROS) production causing early apoptosis [45] or its effect on cell wall integrity genes that leads to cell wall damage and membrane permeabilization [46].…”

Curcumin a novel non-steroidal contraceptive with antimicrobial properties

“…These include generation and accumulation of ROS through accumulation of ergosterol biosynthesis intermediates, resulting in early apoptosis and cell death (74). Curcumin-treated Candida cells also have reduced ergosterol levels and significant differences in the level of molecular species of phosphatidylglycerol and sphingolipids, suggesting that there is modification of membrane lipids in response to curcumin treatment (74). It causes cell wall damage in yeast cells, especially by downregulating genes in the cell wall integrity pathway (75).…”