In vivo RNA sequencing reveals a crucial role of Fus3-Kss1 MAPK pathway in Candida glabrata pathogenicity.

Abstract

The MAPK signaling pathway, mediated by closely related kinases Fus3 and Kss1, is crucial for controlling mating and filamentous growth in Saccharomyces cerevisiae, but this pathway does not significantly impact hyphal development and pathogenicity in Candida albicans, a commensal-pathogenic fungus of humans. Furthermore, deletion of Cpk1, the ortholog of Fus3 in pathogenic fungus Cryptococcus neoformans, has no effect on virulence. Here, we demonstrate that the MAPK pathway is crucial for the pathogenicity of Candida glabrata, a fungus that causes approximately one-third of cases of hematogenously disseminated candidiasis in the United States. This pathway regulates multiple virulence attributes including the induction of iron acquisition genes and adhesins, as well as persistence in macrophages and organs. Our work provides insights into C. glabrata pathogenesis and highlights an example in which regulatory rewiring of a conserved pathway confers a virulent phenotype in a pathogen.