The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales
Author/s
Pérez Arques, Carlos; Navarro Mendoza, María Isabel; Murcia Flores, Laura; Navarro, Eusebio; Garre, Victoriano; [et al.]Date
2021-02Discipline/s
MedicinaSubject/s
RNAiVirulence factor
Exonuclease
Mucormycosis
Abstract
Mucormycosis is a lethal disease caused by Mucorales, which are emerging as human causes that explain the high mortality for this disease. Consequently, the research community is searching for virulence determinants that could be repurposed as targets to develop new treatments against mucormycosis. Our work explores an RNA interference (RNAi)-based approach to find targets involved in the virulence of Mucorales. A transcriptomewide analysis compared sRNAs and their target mRNAs in two Mucor lusitanicus different pathotypes, virulent and avirulent, generating a list of 75 loci selected by their differential sRNA accumulation in these strains. As a proof of concept and validity, an experimental approach characterized two loci showing opposite behavior, confirming that RNAi activity causes their differential expression in the two pathotypes. We generated deletion mutants for two loci and a knockin-strain overexpressing for one of these loci. Their functional analysis in murine virulence a...