Home LiteratureArticle Details
PMID: 2198575 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 15 ·1990-08-00 ·Pages 5950-4

Schmatz DM, Romancheck MA, Pittarelli LA, Schwartz RE, Fromtling RA, Nollstadt KH, Vanmiddlesworth FL, Wilson KE, Turner MJ

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.

MeSH Terms
Animals Anti-Bacterial Agents Antifungal Agents/pharmacology Candida albicans/drug effects Disease Models, Animal Echinocandins Glucans/antagonists & inhibitors,biosynthesis Lung/microbiology,pathology Male Peptides Peptides, Cyclic/pharmacology,therapeutic use Pneumocystis/drug effects,isolation & purification Pneumonia, Pneumocystis/drug therapy,pathology Pyrans/poisoning,therapeutic use Rats Rats, Inbred Strains Sulfamethoxazole/pharmacology,therapeutic use Trimethoprim/pharmacology,therapeutic use
Chemicals
Anti-Bacterial Agents Antifungal Agents Echinocandins Glucans Peptides Peptides, Cyclic Pyrans pneumocandin A(0) L 687781 Trimethoprim Sulfamethoxazole
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Schmatz D M
Department of Biochemical Parasitology, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Romancheck M A
Pittarelli L A
Schwartz R E
Fromtling R A
Nollstadt K H
Vanmiddlesworth F L
Wilson K E
Turner M J
References (32)
32 references, click to expand
  1. Isolation and expression of the Pneumocystis carinii thymidylate synthase gene.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6503-7 PMID: 2671992
  2. Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi.
    Exp Parasitol. 1989 May;68(4):450-61 PMID: 2470612
  3. Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis.
    Antimicrob Agents Chemother. 1990 Feb;34(2):225-8 PMID: 2327770
  4. A NEW PROCEDURE FOR THE IDENTIFICATION OF PNEUMOCYSTIS CARINII CYSTS IN TISSUE SECTIONS AND SMEARS.
    J Clin Pathol. 1963 Jul;16:383-4 PMID: 14044043
  5. Latent Pneumocystis infection of rats, relapse, and chemotherapy.
    Lab Invest. 1966 Oct;15(10):1559-77 PMID: 5297332
  6. Pneumocystis carinii pneumonia in the United States. Epidemiologic, diagnostic, and clinical features.
    Ann Intern Med. 1974 Jan;80(1):83-93 PMID: 4589515
  7. Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis.
    Antimicrob Agents Chemother. 1974 Mar;5(3):289-93 PMID: 4365115
  8. Successful chemoprophylaxis for Pneumocystis carinii pneumonitis.
    N Engl J Med. 1977 Dec 29;297(26):1419-26 PMID: 412099
  9. Combination of pentamidine and trimethoprim-sulfamethoxazole in therapy of Pneumocystis carinii pneumonia in rats.
    Antimicrob Agents Chemother. 1978 Jun;13(6):975-8 PMID: 307941
  10. Papulacandin B: an inhibitor of glucan synthesis in yeast spheroplasts.
    Eur J Biochem. 1979 Jul;97(2):345-51 PMID: 380990
  11. Limited effect of trimethoprim-sulfamethoxazole prophylaxis on Pneumocystis carinii.
    Antimicrob Agents Chemother. 1979 Sep;16(3):333-5 PMID: 315754
  12. Chemoprophylaxis for Pneumocystis carinii pneumonitis: outcome of unstructured delivery.
    Am J Dis Child. 1980 Jul;134(7):643-8 PMID: 6967255
  13. Effect of papulacandin B on the cell wall and growth of Geotrichum lactis.
    J Gen Microbiol. 1983 Jan;129(1):245-50 PMID: 6220134
  14. Efficacy of diaminodiphenylsulfone and other drugs in murine Pneumocystis carinii pneumonitis.
    Antimicrob Agents Chemother. 1984 Oct;26(4):436-40 PMID: 6335017
  15. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases.
    Ann Intern Med. 1985 Nov;103(5):782-6 PMID: 3901852
  16. Successful treatment with aerosolized pentamidine of Pneumocystis carinii pneumonia in rats.
    Antimicrob Agents Chemother. 1987 Jan;31(1):37-41 PMID: 3494424
  17. Fungal 1,3-beta-glucan synthase.
    Methods Enzymol. 1987;138:637-42 PMID: 2955197
  18. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.
    Lancet. 1987 Aug 29;2(8557):480-3 PMID: 2887779
  19. Papulacandins--synthesis and biological activity of papulacandin B derivatives.
    J Antibiot (Tokyo). 1987 Aug;40(8):1146-64 PMID: 3680026
  20. Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia.
    Antimicrob Agents Chemother. 1988 Jan;32(1):96-103 PMID: 3258144
  21. Comparative in vitro activity of LY121019 and amphotericin B against clinical isolates of Candida species.
    Eur J Clin Microbiol Infect Dis. 1988 Feb;7(1):80-1 PMID: 3132386
  22. Pneumocystis carinii pneumonia: therapy and prophylaxis.
    J Infect Dis. 1988 Jul;158(1):254-9 PMID: 2969023
  23. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi.
    Nature. 1988 Aug 11;334(6182):519-22 PMID: 2970013
  24. Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo.
    Antimicrob Agents Chemother. 1988 Jun;32(6):807-13 PMID: 3261959
  25. Aerosolized pentamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia.
    Chest. 1989 Apr;95(4):747-50 PMID: 2784371
  26. L-671,329, a new antifungal agent. I. Fermentation and isolation.
    J Antibiot (Tokyo). 1989 Feb;42(2):163-7 PMID: 2647703
  27. L-671,329, a new antifungal agent. II. Structure determination.
    J Antibiot (Tokyo). 1989 Feb;42(2):168-73 PMID: 2925508
  28. L-671,329, a new antifungal agent. III. In vitro activity, toxicity and efficacy in comparison to aculeacin.
    J Antibiot (Tokyo). 1989 Feb;42(2):174-8 PMID: 2647704
  29. Yeast glucan in the cyst wall of Pneumocystis carinii.
    J Protozool. 1989 Jan-Feb;36(1):21S-22S PMID: 2785184
  30. Cilofungin (LY121019) inhibits Candida albicans (1-3)-beta-D-glucan synthase activity.
    Antimicrob Agents Chemother. 1988 Dec;32(12):1901-3 PMID: 2977537
  31. Clindamycin with primaquine for Pneumocystis carinii pneumonia.
    Lancet. 1989 May 13;1(8646):1046-8 PMID: 2566001
  32. Digital necrosis and disseminated Pneumocystis carinii infection after aerosolized pentamidine prophylaxis.
    Ann Intern Med. 1989 Oct 15;111(8):681-2 PMID: 2802423
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.15.5950
Published
1990-08-00
Pages
5950-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54447
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.15.5950 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2