Downregulation of the Gene Encoding an Intermediate of His-Asp Phosphorelay Signaling in Induces the Same Cellular Effects as the Phenylpyrrole Fungicide Fludioxonil.

Many eukaryotic histidine-to-aspartate (His-Asp) phosphorelay systems consist of three types of signal transducers: a His-kinase (HK), a response regulator (RR), and a histidine-containing phosphotransfer intermediate (HPt). In general, the HPt acts as an intermediate between the HK and the RR and is indispensable for inducing appropriate responses to environmental stresses. In a previous study, we attempted but were unable to obtain deletion mutants of the gene in order to characterize its function in the filamentous fungus . In the present study, we constructed the C strain in which expression is conditionally regulated by the promoter. We constructed C strains with RR gene disruptions (CΔ, CΔ, and CΔΔ). Suppression of YpdA induced by downregulation activated the downstream HogA mitogen-activated protein kinase cascade. YpdA suppression caused severe growth defects and abnormal hyphae, with features such as enhanced septation, a decrease in number of nuclei, nuclear fragmentation, and hypertrophy of vacuoles, both regulated in an SskA-dependent manner. Fludioxonil treatment caused the same cellular responses as suppression. The growth-inhibitory effects of fludioxonil and the lethality caused by downregulation may be caused by the same or similar mechanisms and to be dependent on both the SskA and SrrA pathways.