EFFECTS OF PROTEINASE-INHIBITORS ON THE CUTANEOUS LESION OF SPOROTHRIX-SCHENCKII INOCULATED HAIRLESS MICE

Sporothrix schenckii produces two extracellular proteinases, namely pr oteinase I and II. Proteinase I is a serine proteinase, inhibited by c hymostatin. On the other hand, proteinase II is an aspartic proteinase , inhibited by pepstatin. The addition of either pepstatin or chymosta tin to the culture medium did not inhibit cell growth, however the add ition of both inhibitors strongly inhibited fungal growth. Accordingly , this suggested that extracellular proteinases play an important role in cell growth and that such cell growth may be suppressed if these p roteinases are inhibited. In order to substantiate this speculation in sporotrichosis, the effects of proteinase inhibitors on the cutaneous lesions of mice were studied. Ointments containing 0.1% chymostatin, 0.1% pepstatin and 0.1% chymostatin-0.1% pepstatin were applied twice daily on the inoculation sites of hairless mouse skin, and the time co urses of the lesions examined. The inhibitory effect in vivo on S. sch enckii was similar to that demonstrated in our previous in vitro study . Compared to the control, the time course curve of the number of nodu les present after the application of either pepstatin or chymostatin w as slightly suppressed. The application of both pepstatin and chymosta tin, however, strongly suppressed nodule formation. This study not onl y confirmed the role of 2 proteinases of S, schenckii for fungal growt h in vivo, but also may lead to their use as new topical therapeutic a gents.