Histidine kinases keep fungi safe and vigorous.

Signal transduction in human pathogenic fungi, like in other microorganisms, regulates a number of adaptive transcriptional responses to a variety of environmental cues. Among signal relay proteins, sensor, histidine kinase proteins (HK) are auto-phosphorylated upon perception of an environmental cue, and initiate a phosphorelay that results in transcriptional regulation of genes associated with specific stress signals or multiple stress cues. Human pathogenic fungi utilize HK proteins to adapt to stress, grow, sporulate, undergo morphogenesis, mate, sense anti-fungal drugs, and cause disease. While much is known about HK and RR proteins functionally, the MAPK pathways and downstream transcription factors and gene targets are largely unstudied in human pathogenic fungi. However, as HK proteins are broadly conserved and not apparently in humans, we suggest that they offer exploitation as new targets in anti-fungal drug discovery.