Hog1 signalling in the emerging multidrug resistant fungal pathogen Candida auris

The emerging fungal pathogen Candida auris is responsible for recent global outbreaks caused by genetically divergent clades that, alarmingly, display multi-drug resistance to currently available antifungals. Although not much is known about the pathobiology of this emerging pathogen, we recently found that the Hog1 stress-activated protein kinase (SAPK) in C. auris promotes stress resistance and virulence. SAPKs are evolutionary conserved pathways employed by fungi to promote survival in hostile environments. The aim of this project is to characterise the upstream signalling proteins that relay stress signals to C. auris Hog1. In all eukaryotes, SAPK pathways are comprised of three tiers of kinases with upstream MAPKKK and MAPKKs relaying signals to the terminal SAPK. However, unique to fungi and plants, is an upstream two-component related signalling cascade that transmits signals to the SAPK module, comprising of a histidine kinase, a phosphorelay protein and a response regulator. In C. auris, the proteins that regulate Hog1 activation are unknown. However, bioinformatics analyses of the C. auris genome has allowed for the identification of putative homologues of key Hog1 regulatory proteins including the Pbs2 MAPKK, the Ssk2 MAPKKK, the Ssk1 response regulator, the Ypd1 phosphorelay protein and the Sln1 and Nik1 histidine kinases. Mutational analyses is currently underway to dissect the role of these proteins in Hog1 regulation. Understanding how the Hog1 SAPK is regulated in C. auris may facilitate the identification of fungal specific anti-fungal targets that can be exploited to tackle the threat of this emerging drug resistant pathogen.