Antifungal activity of chitooligosaccharides against the dermatophyte Trichophyton rubrum

Antifungal activity against the dermatophytic fungus Trichophyton rubrum by a well-characterized chitooligosaccharides (COS) sample, hydrolyzed using a recombinant chitosanase, was investigated in vitro and in vivo. The minimum inhibitory concentration (MIC) of COS ranged between 0.25 and 0.50%, which was measured using a microdilution method. Analysis of inhibition rates using an agar diffusion method showed that treatment with 0.5% and 1% COS significantly suppressed T. rubrum cell growth (p<0.05 and p<0.01, respectively, in comparison with untreated control). Morphological changes and structural alterations of cells were observed by TEM. In vivo efficacy of COS in treatment of T. rubrum dermatophytosis was evaluated using a guinea pig model. Skin lesion scores revealed a strong, dose-dependent therapeutic effect of COS. The 5% COS group showed a reduction of skin lesions even greater than that of the positive control group treated with 1% fluconazole (FCZ). Histological analysis revealed no inflammation or tissue destruction in the groups treated with 5% COS or 1% FCZ. Hyperkeratosis was also observed, perhaps resulting from a defensive response of the tissue cells to COS. The findings indicate that COS has excellent potential for development of novel antifungal drugs for clinical treatment/remission of dermatophytoses.