Yeast glucan of Pneumocystis carinii cyst wall: an excellent target for chemotherapy

Abstract

Pneumocystis pneumonia is the most serious opportunistic infection in immunocompromised patients, particularly those with AIDS. Approved therapy is limited to pentamidine and inhibitors of folic acid synthesis, but these drugs show a high rate of adverse reactions in AIDS patients emphasizing the urgent need for additional effective therapies. Progress has, however, been hindered by lack of knowledge about this parasite's cellular characteristics. Previously we reported that beta (1,3)glucan is a major component of the Pneumocystis carinii cyst wall. This study shows that administration of aculeacin A, an inhibitor of beta (1,3)glucan biosynthesis, affects cyst wall formation, inhibits cyst maturation, and prevents severe pneumonia in steroid-treated rats. Thus this study not only demonstrates that beta (1,3)glucan is indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis.