Polysaccharide of Pneumocystis carinii cyst wall as a new target for therapy

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Pneumocystis pneumonia is the most common and 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^<4-7>. Progress has, hawever, been hindered by lack of knowledge about this parasite's cellular characteristics. This study shows that in vitro treatment of P.carinii cysts with beta-1, 3-glucan laminaripentaohydrolase results in cyst wall lysis and loss of Aniline blue staining, a dye which selectively demonstrates 3-1, 3-glucan. Additionally, 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 (yeast glucan) is a major cyst wall component and indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis.