On the antifungal mode of action of metalaxyl, an inhibitor of nucleic acid synthesis in Pythium splendens

Abstract

Growth inhibition of mycelial pellets of Pythium splendens by the acylalanine metalaxyl (CGA 48988) started 4 hr after addition of 0.1 and 0.3 μg/ml of this toxicant. However, at these concentrations germ-tube development in hyphal swellings of this organism was not prevented. According to staining with the DNA-specific fluorochromes nuclear transport into the germ tube as well as nuclear number and shape appeared normal in these germinated hyphal swellings. Likewise, in treated mycelial pellets the nuclei appeared normal in shape, number, and localization. From nutrient solution containing the above concentrations, mycelial suspensions of P. splendens took up only very low quantities of radiolabeled metalaxyl. The requirement of such a small quantity for a fungitoxic effect suggests a rather specific mode of action. After rinsing with distilled water or nutrient solution only ca. 0.1% of the label added remained in or on the mycelium. Using radiolabeled precursors, inhibition was studied in mycelial pellets of P. splendens at growth-inhibiting concentrations. RNA and DNA synthesis appeared already to be strongly inhibited 1 2 hr after addition of the toxicant. Protein synthesis was not inhibited whereas lipid synthesis was almost unaffected at 0.1 μg/ml but strongly affected at 0.3 μg/ml of metalaxyl. Uptake of acetate as a precursor of lipid synthesis was also strongly inhibited at this moment. Although the exact site of action of metalaxyl was not elucidated, it appears to interfere primarily with nucleic acid synthesis in P. splendens in a quite specific way.