The development of resistance in Cladosporium cucumerinum aganst 6-azauracil,a chemotherapeutant of cucumber scab,and its relation to biosynthesis of RNA-precursors

Growth of the fungusCladosporium cucumerinum is inhibited by 6-azauracil (AzU), 6-azauridine (AzUR) and 6-azauridine-5′-monophosphate (AzUMP) on artificial media as well as on the cucumber plant. In cell-free extracts of this fungus the decarboxylation of orotidine-5′-monophosphate (OMP) is inhibited by AzUMP, but not by AzU or AzUR. The fungus itself is able to convert AzU and AzUR to the toxic AzUMP, an example of “lethal synthesis”.By irradiation of conidia with UV two types of AzU-resistant strains were obtained. The first type (III) did not convert AzU to AzUR. Therefore no lethal synthesis occurred when AzU was administered to this strain. The strain was, however, sensitive to AzUR and AzUMP. The second type (R) appeared resistant not only to AzU, but also to AzUR and AzUMP, in spite of the fact that conversion of AzU to AzUR and AzUMP did occur. No indications were obtained that the resistance of the latter type might be due to insufficient permeability towards the inhibitors or to a higher OMP-decarboxylase activity. The presence of an isoenzyme, more resistant to AzUMP than the original OMP-decarboxylase, was ruled out.The tolerance of the cucumber plant to AzU was paralleled by an extremely high activity of the enzyme OMP-decarboxylase in comparison with that found in the fungus.