Treatment of Pneumocystis Carinii Pneumonia with 1,3-beta-glucan Synthesis Inhibitors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Aug 1

PMID 2198575

Citations 56

Authors

D M Schmatz

M A Romancheck

L A Pittarelli

R E Schwartz

R A Fromtling

K H Nollstadt

F L VanMiddlesworth

K E Wilson

M J Turner

Affiliations

Soon will be listed here.

Abstract

Pneumocystis carinii pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease. Recent evidence has suggested that P. carinii is related to fungi and that the wall of the cyst form contains 1,3-beta-glucan as a major constituent. Based on this, several proposed 1,3-beta-glucan synthesis inhibitors were evaluated for their ability to control P. carinii pneumonia in vivo. Compounds from two classes of 1,3-beta-glucan synthesis inhibitors, the echinocandins and papulacandins, were found to be effective against P. carinii.

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References

Edman U, Edman J, Lundgren B, Santi D . Isolation and expression of the Pneumocystis carinii thymidylate synthase gene. Proc Natl Acad Sci U S A. 1989; 86(17):6503-7. PMC: 297872. DOI: 10.1073/pnas.86.17.6503. View

Stringer S, Stringer J, Blase M, Walzer P, Cushion M . Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi. Exp Parasitol. 1989; 68(4):450-61. DOI: 10.1016/0014-4894(89)90130-6. View

Hughes W, Gray V, Gutteridge W, Latter V, Pudney M . Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1990; 34(2):225-8. PMC: 171561. DOI: 10.1128/AAC.34.2.225. View

CHALVARDJIAN A, GRAWE L . A NEW PROCEDURE FOR THE IDENTIFICATION OF PNEUMOCYSTIS CARINII CYSTS IN TISSUE SECTIONS AND SMEARS. J Clin Pathol. 1963; 16:383-4. PMC: 480584. DOI: 10.1136/jcp.16.4.383. View

FRENKEL J, GOOD J, Shultz J . Latent Pneumocystis infection of rats, relapse, and chemotherapy. Lab Invest. 1966; 15(10):1559-77. View

Walzer P, Perl D, Krogstad D, Rawson P, Schultz M . Pneumocystis carinii pneumonia in the United States. Epidemiologic, diagnostic, and clinical features. Ann Intern Med. 1974; 80(1):83-93. DOI: 10.7326/0003-4819-80-1-83. View

Hughes W, McNabb P, Makres T, Feldman S . Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1974; 5(3):289-93. PMC: 428962. DOI: 10.1128/AAC.5.3.289. View

Hughes W, Kuhn S, Chaudhary S, Feldman S, Verzosa M, AUR R . Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med. 1977; 297(26):1419-26. DOI: 10.1056/NEJM197712292972602. View

Kluge R, Spaulding D, Spain A . Combination of pentamidine and trimethoprim-sulfamethoxazole in therapy of Pneumocystis carinii pneumonia in rats. Antimicrob Agents Chemother. 1978; 13(6):975-8. PMC: 352374. DOI: 10.1128/AAC.13.6.975. View

10.

Baguley B, Rommele G, Gruner J, Wehrli W . Papulacandin B: an inhibitor of glucan synthesis in yeast spheroplasts. Eur J Biochem. 1979; 97(2):345-51. DOI: 10.1111/j.1432-1033.1979.tb13120.x. View

11.

Hughes W . Limited effect of trimethoprim-sulfamethoxazole prophylaxis on Pneumocystis carinii. Antimicrob Agents Chemother. 1979; 16(3):333-5. PMC: 352856. DOI: 10.1128/AAC.16.3.333. View

12.

Wilber R, Feldman S, Malone W, Ryan M, AUR R, Hughes W . Chemoprophylaxis for Pneumocystis carinii pneumonitis: outcome of unstructured delivery. Am J Dis Child. 1980; 134(7):643-8. DOI: 10.1001/archpedi.1980.02130190011004. View

13.

Perez P, GARCIA-ACHA I, Duran A . Effect of papulacandin B on the cell wall and growth of Geotrichum lactis. J Gen Microbiol. 1983; 129(1):245-50. DOI: 10.1099/00221287-129-1-245. View

14.

Hughes W, Smith B . Efficacy of diaminodiphenylsulfone and other drugs in murine Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1984; 26(4):436-40. PMC: 179940. DOI: 10.1128/AAC.26.4.436. View

15.

Pearson R, Hewlett E . Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases. Ann Intern Med. 1985; 103(5):782-6. DOI: 10.7326/0003-4819-103-5-782. View

16.

Debs R, BLUMENFELD W, Brunette E, Straubinger R, Montgomery A, Lin E . Successful treatment with aerosolized pentamidine of Pneumocystis carinii pneumonia in rats. Antimicrob Agents Chemother. 1987; 31(1):37-41. PMC: 174647. DOI: 10.1128/AAC.31.1.37. View

17.

CABIB E, Kang M . Fungal 1,3-beta-glucan synthase. Methods Enzymol. 1987; 138:637-42. DOI: 10.1016/0076-6879(87)38057-7. View

18.

Montgomery A, Debs R, Luce J, Corkery K, Turner J, Brunette E . Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet. 1987; 2(8557):480-3. DOI: 10.1016/s0140-6736(87)91794-6. View

19.

Traxler P, Tosch W, Zak O . Papulacandins--synthesis and biological activity of papulacandin B derivatives. J Antibiot (Tokyo). 1987; 40(8):1146-64. DOI: 10.7164/antibiotics.40.1146. View

20.

Walzer P, Kim C, Foy J, Linke M, Cushion M . Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1988; 32(1):96-103. PMC: 172106. DOI: 10.1128/AAC.32.1.96. View