Effect of NND-318 on the Ultrastructure of Trichophyton mentagrophytes as Observed by Scanning and Transmission Electron Microscopy

Effect of NND-318 on the morphology of growing hyphae of Trichophyton mentagrophytes was observed by scanning and transmission electron microscopy. Microconidia of T. mentagrophytes were inoculated on a slide-culture and incubated at 27°C for 60 hours. In the control culture grown without the drug, the hyphae showed a smooth surface, straight extensions and consistent width. In the culture grown with NND-318 at concentrations ranging from 0.08 to 0.4 ng/ml, scanning electron microscopy revealed that hyphae were wavy, curled and bent with wrinkled surface. In ultrathin sections, thickening of the cell wall, accumulation of electron denes granular structures formed within the cell wall, and the number of cytoplasmic lipid droplets were observed to increase with drug concentration. At concentrations ranging from 0.8 to 1.6ng/ml, hyphae were short in length and the surface was heavily wrinkled. At concentrations above 4 ng/ml, germination of inoculated conidia was not observed. Similar morphological changes were seen in T. mentagrophytes treated with higher concentrations of bifonazole. These results suggest that NND-318, at concentrations considerably lower than those of other imidazoles, is able to inhibit hyphal growth of T. mentagrophytes with thickening of cell wall, accumulation of electron dense granules formed in the cell wall and increased number of cytoplasmic lipid droplets.