Stress sensitivity of a fission yeast strain lacking histidine kinases is rescued by the ectopic expression of Chk1 from Candida albicans

Abstract

The development of new drugs against the pathogenic yeast Candida albicans is compelling and the evolution of relevant bioassays is important to achieve this goal. Promising drug targets are proteins that lack human counterparts which are true for the His-to-Asp phosphorelay signal transduction systems, important for stress sensing in bacteria, fungi, and plants. In the pathogenic yeast, Candida albicans, the CaChk1 histidine kinase is a trigger of the pathway that leads to a switch from yeast to hyphal growth necessary for invasion. Intriguingly, the model yeast Schizosaccharomyces pombe has a similar phosphorelay system, with three histidine kinases named Mak1, Mak2, and Mak3, which are important for the prevention of aberrant mating and sporulation on rich media. This study uncovered distinct functions for the three histidine kinases; Mak1 alone or Mak2 and Mak3 together were sufficient for the repression of the meiotic cycle when nutrients were available. Moreover, strains lacking histidine kinase genes were sensitive to various types of stress conditions in an auxotrophic strain background, while the stress sensitivity was lost in prototrophic strains. Finally, the stress sensitivity of a S. pombe strain that lacks endogenous histidine kinases could be complemented by the ectopic expression of the CaChk1 histidine kinase from C. albicans. This finding opens up for the possibility to perform a drug screen with a biological read-out in S. pombe to find inhibitors of CaChk1.Electronic supplementary materialThe online version of this article (doi:10.1007/s00294-016-0644-9) contains supplementary material, which is available to authorized users.

Map of dimorphic switching‑related signaling pathways inSporothrix schenckiibased on its transcriptome

“…Several studies, including our previous study focusing on class III HHK (Os-1 ortholog) in human dimorphic pathogens, have revealed conserved roles in fungicide resistance, osmotic stress resistance and pathogenicity, in addition to roles in cell wall integrity, asexual development and dimorphism ( 6 , 17 , 33 , 34 ). Furthermore, SlnA (class VI) in T. marneffei , Chk1 (class VIII) in C. albicans , and TcsA (class IV) in Aspergillus nidulans were revealed to be associated with osmotic stress resistance, HOG MAPK regulation, the dimorphic transition and development under standard growth conditions ( 7 , 35 ). As multiple histamine kinases may compensate for each other in S. schenckii ( Fig.…”