Faculty of Dentistry, The University of Hong Kong, Hong Kong Special Administrative Region; Quorum Sensing Laboratory, Centre of Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to Be University, Thanjavur, India.
Green Pyramid Biotech Private Limited, Pune, India.
Colloids Surf B Biointerfaces. 2021 Apr;200:111617. doi: 10.1016/j.colsurfb.2021.111617. Epub 2021 Feb 6.
Candida albicans is an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, due to their biofilm lifestyle. The ability of C. albicans to invade human tissues is due to its filamentation. Therefore, inhibition of biofilms and filamentation of the yeast are high value targets to develop the next-generation antifungals. Curcumin (CU) is a natural polyphenol with excellent pharmacological attributes, but limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility. Sophorolipids (SL) are biologically-derived surfactants that serve as efficient carriers of hydrophobic molecules such as curcumin into biofilms. Here, we synthesised a curcumin-sophorolipid nanocomplex (CUSL), and comprehensively evaluated its effects on C. albicans biofilms and filamentation. Our results demonstrated that sub-inhibitory concentration of CUSL (9.37 μg/mL) significantly inhibited fungal 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 nanocomplex 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-fungal agent with biofilm penetrative potential.
白色念珠菌是一种机会性真菌病原体,由于其生物膜生活方式,对当代抗真菌药物具有高度耐药性。白色念珠菌侵袭人体组织的能力归因于其菌丝形成。因此,抑制酵母的生物膜和菌丝形成是开发下一代抗真菌药物的高价值目标。姜黄素(CU)是一种具有出色药理特性的天然多酚,但溶解度差、耐酸和耐酶性等限制因素阻碍了其实际应用。槐糖脂(SL)是生物衍生的表面活性剂,可作为姜黄素等疏水分子有效进入生物膜的载体。在这里,我们合成了姜黄素-槐糖脂纳米复合物(CUSL),并全面评估了其对白色念珠菌生物膜和菌丝形成的影响。我们的结果表明,亚抑制浓度的 CUSL(9.37μg/mL)显著抑制真菌对底物的黏附,随后抑制生物膜的发展、成熟和菌丝形成。这种作用与生物膜、黏附素和菌丝调节基因的特定选择组的显著下调有关。总之,姜黄素-槐糖脂纳米复合物是白色念珠菌两种主要毒力特性(生物膜形成和菌丝形成)的有效抑制剂,因此凸显了其作为具有生物膜穿透潜力的潜在抗真菌剂的前景。