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bioRxiv · 10.1101/2020.08.12.244186

Curcumin-Sophorolipid nano-conjugate inhibits Candida albicans filamentation and biofilm development

Rajasekar, V.·Darne, P.·Prabhune, A.·Kao, R. Y. T.·Solomon, A. P.·Ramage, G.·Samaranayake, L.·Neelakantan, P.
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Abstract

Candida albicans is an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, and a major reason for this appears to be their predominant, filamentation-mediated, biofilm lifestyle. Hence, agents that inhibit biofilms and filamentation of the yeast offer promise as next-generation antifungals. Curcumin is a natural polyphenol with several beneficial pharmacological attributes, yet limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility. Sophorolipids are biologically-derived surfactants that serve as efficient carriers and delivery agents of hydrophobic molecules, such as curcumin, into biofilms. The aim of this study was to investigate the effects of a novel, curcumin-sophorolipid (CU-ASL) nano-conjugate on Candida albicans biofilms and filamentation. The effects of CU and ASL, in combination, and alone, were investigated on planktonic cells of the yeast. The effects of sub-inhibitory concentrations of the compounds were investigated on biofilm biomass and biofilm architecture. Their effects on filamentation was compared by scanning electron microscopic imaging, and gene expression analysis by qRT-PCR. Our results demonstrated that sub-inhibitory concentration of CU-ASL (9.37 {micro}g/mL) significantly inhibited candidal adhesion to substrates, and subsequent biofilm development, maturation, and filamentation. This effect was associated with significant downregulation of a select group of biofilm, adhesins, and hyphal regulatory genes. In conclusion, the curcumin-sophorolipid nano-conjugate is a potent inhibitor of the two major virulence attributes of C. albicans, biofilm formation and filamentation, thus highlighting its promise as a putative anti-candidal agent with low toxicity and biofilm penetrative potential.

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Rajasekar, V., Darne, P., Prabhune, A., Kao, R. Y. T., Solomon, A. P., Ramage, G., Samaranayake, L., Neelakantan, P.. 2020-08-12. Curcumin-Sophorolipid nano-conjugate inhibits Candida albicans filamentation and biofilm development. https://doi.org/10.1101/2020.08.12.244186

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