Combined application of antisense oligomers to control transcription factors of Candida albicans biofilm formation

Abstract

Antisense oligomers (ASOs) have been little exploited to control determinants of Candida albicans virulence. Biofilm formation is an important virulence factor of C. albicans, that is regulated by a complex network of transcription factors (such as EFG1, BRG1 and ROB1). Thus, the main goal of this work was to project ASOs, based on the 2'-OMethyl chemical modification, to target BRG1 and ROB1 mRNA and to validate its application either alone or in combination with the EFG1 mRNA target, to reduce C. albicans biofilm formation. The ability of ASOs to control gene expression was evaluate by qRT-PCR. The effect on biofilm formation was determined by the total biomass quantification, and simultaneously the carbohydrates and proteins reduction on extracellular matrix. It was verified that all the oligomers were able to reduce the levels of gene expression and the ability of C. albicans to form biofilms. Furthermore, the combined application of the cocktail of ASOs enhances the inhibition of C. albicans biofilm formation, minimizing biofilm thickness by reducing the quantity of matrix content (protein and carbohydrate). So, our work confirms that ASOs are useful tools for research and therapeutic development on the control of Candida species biofilm formation.