The Candida auris Hog1 MAP kinase is essential for the colonization of murine skin and systemic infection
Candida auris, a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic C. auris infections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that C. auris, unlike most Candida species, displays unique skin tropism and can stay on human skin for a prolonged period. However, the molecular mechanisms responsible for C. auris­ skin colonization, intradermal persistence, and systemic virulence are poorly understood. Here, we report that C. auris Hog1 mitogen-activated protein kinase (MAPK) is essential for efficient skin colonization, intradermal persistence, as well as, systemic virulence. RNA-seq analysis of wildtype parental and hog1D mutant strains from YPD-grown cultures revealed marked down-regulation of genes involved in processes such as cell adhesion, cell-wall rearrangement, and pathogenesis in hog1D mutant compared to the wildtype parent. In agreement, we found a prominent role for Hog1 in maintaining cell-wall architecture, as the hog1D mutant demonstrated a significant increase in cell-surface b-glucan exposure and a concomitant reduction in chitin content. Additionally, we observed that Hog1 was required for biofilm formation in vitro and fungal survival when challenged with primary murine macrophages and neutrophils ex vivo. Collectively, these findings have important implications for understanding the C. auris skin adherence mechanisms and penetration of skin epithelial layers preceding bloodstream infections. Overall design: We performed RNA-seq analysis of logarithmically growing Candida auris isolates in the Yeast Extract Peptone Dextrose broth medium (YPD; 1% yeast extract, 2% peptone, and 2% dextrose) at 30°C. We sequenced parent and HOG1 deletion strain in biological triplicates