Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1974 Sep;6(3):282–289. doi: 10.1128/aac.6.3.282

In Vitro And In Vivo Activity of 5-Fluorocytosine on Acanthamoeba

A R Stevens a, W D O'Dell a,1
PMCID: PMC444638  PMID: 15830474

Abstract

The results of our studies indicated that the avirulent Neff strain of Acanthamoeba was more susceptible to the activity of the anti-metabolite 5-fluorocytosine (5-FC) than was the virulent A-1 strain or a mouse brain reisolate of this strain, designated A-3. Results of competition experiments in which cultures were exposed simultaneously to 5-FC and either uracil, thymidine, or both uracil and thymidine demonstrated that the drug was directed against both deoxyribonucleic acid and ribonucleic acid in the avirulent strain, whereas ribonucleic acid was mainly affected in the virulent amebas. Concentrations >10 μg of 5-FC per ml were amebicidal to the avirulent strain; lower concentrations of the drug, which only affected growth slightly, significantly impaired the capacity of the cells to spontaneously encyst in stationary-phase cultures. On the other hand, the virulent strains were capable of growing in the presence of 5-FC (40 μg/ml) after an initial period of susceptibility. After a few transfers in growth medium lacking the drug, 5-FC-treated virulent amebas exhibited growth parameters typical of untreated cells. However, after successive subcultures in drug-free medium, 5-FC-treated cells lost their resistance and were again susceptible to the drug. This result suggested that the capacity of the cells to develop resistance resulted from a drug-induced mechanism. Spontaneous encystment, which was normally minimal in stationary-phase A-1 or A-3 cultures, was enhanced in A-3 but not A-1 cultures treated with 5-FC (>30 μg/ml). Results obtained from experiments to determine the effectiveness of 5-FC in protecting mice experimentally infected with either A-1 or A-3 amebas indicated that the clinical usefulness of 5-FC may be limited by the capacity of the amebas to develop resistance.

Full text

PDF
282

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K., Jamieson A. Primary amoebic meningoencephalitis. Lancet. 1972 Apr 22;1(7756):902–903. doi: 10.1016/s0140-6736(72)90772-6. [DOI] [PubMed] [Google Scholar]
  2. Block E. R., Bennett J. E. The combined effect of 5-fluorocytosine and amphotericin B in the therapy of murine cryptococcosis. Proc Soc Exp Biol Med. 1973 Feb;142(2):476–480. doi: 10.3181/00379727-142-37049. [DOI] [PubMed] [Google Scholar]
  3. Block E. R., Jennings A. E., Bennett J. E. 5-fluorocytosine resistance in Cryptococcus neoformans. Antimicrob Agents Chemother. 1973 Jun;3(6):649–656. doi: 10.1128/aac.3.6.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carter R. F. Primary amoebic meningo-encephalitis: clinical, pathological and epidemiological features of six fatal cases. J Pathol Bacteriol. 1968 Jul;96(1):1–25. doi: 10.1002/path.1700960102. [DOI] [PubMed] [Google Scholar]
  5. Carter R. F. Sensitivity to amphotericin B of a Naegleria sp. isolated from a case of primary amoebic meningoencephalitis. J Clin Pathol. 1969 Jul;22(4):470–474. doi: 10.1136/jcp.22.4.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casemore D. P. Sensitivity of Hartmannella (Acanthamoeba) to 5-fluorocytosine, hydroxystilbamidine, and other substances. J Clin Pathol. 1970 Nov;23(8):649–652. doi: 10.1136/jcp.23.8.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Culbertson C. G., Ensminger P. W., Overton W. M. Pathogenic Naegleria sp.--study of a strain isolated from human cerebrospinal fluid. J Protozool. 1968 May;15(2):353–363. doi: 10.1111/j.1550-7408.1968.tb02136.x. [DOI] [PubMed] [Google Scholar]
  8. Culbertson C. G. The pathogenicity of soil amebas. Annu Rev Microbiol. 1971;25:231–254. doi: 10.1146/annurev.mi.25.100171.001311. [DOI] [PubMed] [Google Scholar]
  9. Duma R. J., Rosenblum W. I., McGehee R. F., Jones M. M., Nelson E. C. Primary amoebic meningoencephalitis caused by Naegleria. Two new cases, response to amphotericin B, and a review. Ann Intern Med. 1971 Jun;74(6):923–931. doi: 10.7326/0003-4819-74-6-923. [DOI] [PubMed] [Google Scholar]
  10. Heidelberger C. Fluorinated pyrimidines. Prog Nucleic Acid Res Mol Biol. 1965;4:1–50. doi: 10.1016/s0079-6603(08)60783-7. [DOI] [PubMed] [Google Scholar]
  11. Holt R. J., Newman R. L. The antimycotic activity of 5-fluorocytosine. J Clin Pathol. 1973 Mar;26(3):167–174. doi: 10.1136/jcp.26.3.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jager B. V., Stamm W. P. Brain abscesses caused by free-living amoeba probably of the genus Hartmannella in a patient with Hodgkin's disease. Lancet. 1972 Dec 23;2(7791):1343–1345. doi: 10.1016/s0140-6736(72)92781-x. [DOI] [PubMed] [Google Scholar]
  13. Kenney M. The Micro-Kolmer complement fixation test in routine screening for soil ameba infection. Health Lab Sci. 1971 Jan;8(1):5–10. [PubMed] [Google Scholar]
  14. Medoff G., Comfort M., Kobayashi G. S. Synergistic action of amphotericin B and 5-fluorocytosine against yeast-like organisms. Proc Soc Exp Biol Med. 1971 Nov;138(2):571–574. doi: 10.3181/00379727-138-35943. [DOI] [PubMed] [Google Scholar]
  15. Medoff G., Kobayashi G. S., Kwan C. N., Schlessinger D., Venkov P. Potentiation of rifampicin and 5-fluorocytosine as antifungal antibiotics by amphotericin B (yeast-membrane permeability-ribosomal RNA-eukaryotic cell-synergism). Proc Natl Acad Sci U S A. 1972 Jan;69(1):196–199. doi: 10.1073/pnas.69.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neff R. J., Neff R. H. The biochemistry of amoebic encystment. Symp Soc Exp Biol. 1969;23:51–81. [PubMed] [Google Scholar]
  17. Robert V. B., Rorke L. B. Primary amebic encephalitis, probably from Acanthamoeba. Ann Intern Med. 1973 Aug;79(2):174–179. doi: 10.7326/0003-4819-79-2-174. [DOI] [PubMed] [Google Scholar]
  18. Shadomy S. Further in vitro studies with 5-fluorocytosine. Infect Immun. 1970 Oct;2(4):484–488. doi: 10.1128/iai.2.4.484-488.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shadomy S. In vitro studies with 5-fluorocytosine. Appl Microbiol. 1969 Jun;17(6):871–877. doi: 10.1128/am.17.6.871-877.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stevens A. R., O'Dell W. D. The influence of growth medium on axenic cultivation of virulent and avirulent Acanthamoeba. Proc Soc Exp Biol Med. 1973 Jun;143(2):474–478. doi: 10.3181/00379727-143-37346. [DOI] [PubMed] [Google Scholar]
  21. Stevens A. R., Pachler P. F. RNA synthesis and turnover during density-inhibited growth and encystment of Acanthamoeba castellanii. J Cell Biol. 1973 May;57(2):525–537. doi: 10.1083/jcb.57.2.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Utz J. P. Flucytosine. N Engl J Med. 1972 Apr 6;286(14):777–778. doi: 10.1056/NEJM197204062861412. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES