LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, CEB - Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
Med Mycol. 2021 Oct 4;59(10):1024-1031. doi: 10.1093/mmy/myab033.
Although antisense oligomers (ASOs) have been successfully utilized to control gene expression, they have been little exploited to control Candida albicans virulence's determinants. Filamentation is an important virulence factor of C. albicans, and RAS1 and RIM101 genes are involved in its regulation. Thus, the main goal of this work was to project ASOs, based on 2'-OMethyl chemical modification, to target RAS1 and RIM101 mRNA and to validate its application either alone or in combination, to reduce Candida filamentation in different human body fluids. It was verified that both, anti-RAS1 2'OMe and anti-RIM101 2'OMe oligomers, were able to reduce the levels of RAS1 and RIM101 genes' expression and to significantly reduce C. albicans filamentation. Furthermore, the combined application of anti-RAS1 2'OMe oligomer and anti-RIM101 2'OMe oligomer enhances the control of C. albicans filamentation in artificial saliva and urine. Our work confirms that ASOs are useful tools for research and therapeutic development on the control of candidiasis.
尽管反义寡核苷酸 (ASO) 已成功用于控制基因表达，但它们在控制白色念珠菌毒力决定因素方面的应用却很少。菌丝形成是白色念珠菌的一个重要毒力因子，RAS1 和 RIM101 基因参与其调控。因此，这项工作的主要目标是设计基于 2'-OMethyl 化学修饰的 ASO，靶向 RAS1 和 RIM101 mRNA，并验证其单独或联合应用在不同人体液中降低白色念珠菌菌丝形成的效果。结果证实，抗-RAS1 2'OMe 和抗-RIM101 2'OMe 寡核苷酸均能降低 RAS1 和 RIM101 基因表达水平，并显著降低白色念珠菌的菌丝形成。此外，抗-RAS1 2'OMe 寡核苷酸和抗-RIM101 2'OMe 寡核苷酸的联合应用增强了对人工唾液和尿液中白色念珠菌菌丝形成的控制。我们的工作证实，ASO 是研究和治疗控制念珠菌病的有用工具。
