The combined application of the anti-RAS1 and anti-RIM101 2'-OMethylRNA oligomers enhances Candida albicans filamentation control

Med Mycol. 2021 Oct 4;59(10):1024-1031. doi: 10.1093/mmy/myab033.

Abstract

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.

Keywords: Candidiasis; nucleic acid mimics; therapeutic oligomers; virulence.

Plain language summary

This work aimed to project antisense oligomers to control Candida albicans filamentation. The results revealed that the projected oligomers, anti-RAS1 2'OMe and anti-RIM101 2'OMe, were able to control RAS1 and RIM101 gene expression and to significantly reduce C. albicans filamentation.

MeSH terms

  • Animals
  • Candida
  • Candida albicans* / genetics
  • Candidiasis* / prevention & control
  • Candidiasis* / veterinary
  • Fungal Proteins / genetics
  • RNA, Messenger
  • Virulence Factors

Substances

  • Fungal Proteins
  • RNA, Messenger
  • Virulence Factors