Functional characterization of two survival factor 1 genes in Mucor lusitanicus

Abstract

ABSTRACT Survival factor 1 (Svf1) protein has been described in some ascomycetous fungi where it was found to be contributing to several essential physiological processes, such as response to osmotic, oxidative and cold stresses, sphingolipid biosynthesis, morphogenesis, sporulation, antifungal resistance, and pathogenicity. It was also suggested that it can be a novel central regulator affecting the expression of various genes. In the present study, function of this protein and the encoding genes is described for the first time in a fungus (i.e., in Mucor lusitanicus) belonging to the order Mucorales. M. lusitanicus has two putative svf1 genes named svf1a and svf1b. Expression of both genes was proven. Although the expression of svf1a was affected by several environmental stresses and knocking out the gene affected adaptation to low temperatures and the sporulation ability, the main survival factor functions, such as participation in the maintenance of the viability, the response to oxidative and cold stresses, and the sphingolipid biosynthesis, could be associated with Svf1b, suggesting a central regulatory role to this protein. Interestingly, knockout of both genes affected the pathogenicity of the fungus in a Drosophila model.IMPORTANCEMucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.

Keywords

• mucormycosis
• key regulator
• cold stress
• sphingolipid biosynthesis
• pathogenicity
• CRISPR-Cas9