A novel functional assay for fungal histidine kinases group III reveals the role of HAMP domains for fungicide sensitivity

► We achieved functional expression of the group III histidine kinase CaNik1 in S. cerevisiae after replacement of the C. albicans specific serine codons. ► The S. cerevisiae transformant acquired sensitivity to fungicides, such as fludioxonil, iprodione, ambruticin VS-3 and jerangolid A, to which the wild-type strain was resistant. ► The sensitivity to the fungicides was dependent on a functional Hog1-pathway, which is the signal transduction pathway leading to osmotic stress resistance. ► Sequence analysis of the CaNik1 gene, in particular of the N-terminal amino acid repeat domains, led to the identification of 9 HAMP domains instead of the previously known five. These domains are arranged in a concatenated paired structure. ► To study the function of the HAMP domains for fungicide sensitivity, we precisely deleted pairs of HAMP domains to not disrupt the helical structure of these domains. ► The sensitivity of strains carrying truncated proteins to the fungicides was lower than that of the transformant with the full-length protein. The influence of domain deletion was compound dependent. However, a decisive role of the HAMP domains for the sensitivity to fungicides can be concluded.