Anti- EFG1 2'- O MethylRNA oligomer inhibits Candida albicans filamentation and attenuates the candidiasis in Galleria mellonella

Daniela Araújo; Dalila Mil-Homens; Mariana Henriques; Sónia Silva

doi:10.1016/j.omtn.2021.12.018

Anti- EFG1 2'- O MethylRNA oligomer inhibits Candida albicans filamentation and attenuates the candidiasis in Galleria mellonella

Mol Ther Nucleic Acids. 2021 Dec 16:27:517-523. doi: 10.1016/j.omtn.2021.12.018. eCollection 2022 Mar 8.

Authors

Daniela Araújo¹, Dalila Mil-Homens², Mariana Henriques¹, Sónia Silva^{1

3}

Affiliations

¹ LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, CEB - Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
² iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Lisbon University, 1049-001 Lisbon, Portugal.
³ National Institute for Agrarian and Veterinary Research, Vairão, 4485-655 Vila do Conde, Portugal.

Abstract

EFG1 is a central transcriptional regulator of filamentation that is an important virulence factor of Candida albicans. This study serves to assess in vivo the applicability of the anti-EFG1 2'-OMethylRNA oligomer for inhibiting C . albicans filamentation and to attenuate candidiasis, using the Galleria mellonella model. For that, larvae infected with a lethal concentration of C. albicans cells were treated with a single dose and with a double dose of the anti-EFG1 2'OMe oligomer (at 40 and 100 nM). The anti-EFG1 2'OMe oligomer toxicity and effect on larvae survival was evaluated. No evidence of anti-EFG1 2'OMe oligomer toxicity was observed and the treatment with double dose of 2'OMe oligomer empowered larvae survival over 24 h (by 90%-100%) and prolonged its efficacy until 72 h of infection (by 30%). Undoubtedly, this work validates the in vivo therapeutic potential of anti-EFG1 2'OMe oligomer for controlling C. albicans infections.

Keywords: 2′-OMethyl chemical modification; Galleria mellonella; antisense oligonucleotides; candidiasis; virulence.