Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Aug 1;160(2):353–368. doi: 10.1084/jem.160.2.353

Virulence of Entamoeba histolytica trophozoites. Effects of bacteria, microaerobic conditions, and metronidazole

PMCID: PMC2187461  PMID: 6088660

Abstract

The association of axenically grown trophozoites of Entamoeba histolytica strains HK-9 or HM-1:IMSS with various types of gram- negative bacteria for relatively short periods markedly increased their virulence, as evidenced by their ability to destroy monolayers of tissue-cultured cells. Interaction of trophozoites with bacteria that were heat inactivated, glutaraldehyde fixed, or disrupted by sonication, or bacteria treated with inhibitors of protein synthesis, did not augment amebic virulence. Lethally irradiated bacteria, however, retained their stimulative properties and trophozoites that ingested bacteria were protected from the toxic effects of added hydrogen peroxide. An increase in virulent properties of amebae was also found in experiments carried out under microaerobic conditions (5% O2, 10% CO2). The augmentation of amebic virulence due to association with bacteria was specifically blocked by metronidazole, but not by tetracycline or aminoglycosides, and the rate of metronidazole uptake in stimulated trophozoites was two to three times higher. The results obtained suggest that virulence of axenically grown E. histolytica trophozoites may depend to a considerable extent on the cell's reducing power. Both microaerobic conditions and the association with bacteria apparently stimulate the electron transport system of the ameba. Bacteria may function as broad range scavengers for oxidized molecules and metabolites through the contribution of enzymatic systems, components, or products.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Band R. N., Cirrito H. Growth response of axenic Entamoeba histolytica to hydrogen, carbon dioxide, and oxygen. J Protozool. 1979 May;26(2):282–286. doi: 10.1111/j.1550-7408.1979.tb02781.x. [DOI] [PubMed] [Google Scholar]
  2. Bornside G. H., Donovan W. E., Myers M. B. Intracolonic tensions of oxygen and carbon dioxide in germfree, conventional, and gnotobiotic rats. Proc Soc Exp Biol Med. 1976 Feb;151(2):437–441. doi: 10.3181/00379727-151-39229. [DOI] [PubMed] [Google Scholar]
  3. Bos H. J. Entamoeba histolytica: cytopathogenicity of intact amebae and cell-free extracts; isolation and characterization of an intracellular toxin. Exp Parasitol. 1979 Jun;47(3):369–377. doi: 10.1016/0014-4894(79)90089-4. [DOI] [PubMed] [Google Scholar]
  4. Bos H. J., van de Griend R. J. Virulence and toxicity of axenic Entamoeba histolytica. Nature. 1977 Jan 27;265(5592):341–343. doi: 10.1038/265341a0. [DOI] [PubMed] [Google Scholar]
  5. Bracha R., Mirelman D. Adherence and ingestion of Escherichia coli serotype 055 by trophozoites of Entamoeba histolytica. Infect Immun. 1983 Jun;40(3):882–887. doi: 10.1128/iai.40.3.882-887.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bursuker I., Goldman R. Quantitative and functional differences induced in bone marrow-derived mononuclear phagocytes by inflammatory stimuli. J Reticuloendothel Soc. 1979 May;25(5):533–544. [PubMed] [Google Scholar]
  7. Carlsson J., Nyberg G., Wrethén J. Hydrogen peroxide and superoxide radical formation in anaerobic broth media exposed to atmospheric oxygen. Appl Environ Microbiol. 1978 Aug;36(2):223–229. doi: 10.1128/aem.36.2.223-229.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Das S. R., Ghoshal S. Restoration of virulence to rat of axenically grown Entamoeba histolytica by cholesterol and hamster liver passage. Ann Trop Med Parasitol. 1976 Dec;70(4):439–443. doi: 10.1080/00034983.1976.11687144. [DOI] [PubMed] [Google Scholar]
  9. Diamond L. S., Harlow D. R., Cunnick C. C. A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba. Trans R Soc Trop Med Hyg. 1978;72(4):431–432. doi: 10.1016/0035-9203(78)90144-x. [DOI] [PubMed] [Google Scholar]
  10. Diamond L. S., Phillips B. P., Bartgis I. L. A comparison of the virulence of nine strains of axenically cultivated E. histolytica in hamster liver. Arch Invest Med (Mex) 1974;5(Suppl 2):423–426. [PubMed] [Google Scholar]
  11. Diamond L. S. Techniques of axenic cultivation of Entamoeba histolytica Schaudinn, 1903 and E. histolytica-like amebae. J Parasitol. 1968 Oct;54(5):1047–1056. [PubMed] [Google Scholar]
  12. Entner N. Emetine binding to ribosomes of Entamoeba histolytica--inhibition of protein synthesis and amebicidal action. J Protozool. 1979 May;26(2):324–328. doi: 10.1111/j.1550-7408.1979.tb02789.x. [DOI] [PubMed] [Google Scholar]
  13. Eshdat Y., Ofek I., Yashouv-Gan Y., Sharon N., Mirelman D. Isolation of a mannose-specific lectin from Escherichia coli and its role in the adherence of the bacteria to epithelial cells. Biochem Biophys Res Commun. 1978 Dec 29;85(4):1551–1559. doi: 10.1016/0006-291x(78)91179-8. [DOI] [PubMed] [Google Scholar]
  14. Gadasi H., Kessler E. Correlation of virulence and collagenolytic activity in Entamoeba histolytica. Infect Immun. 1983 Feb;39(2):528–531. doi: 10.1128/iai.39.2.528-531.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ghadirian E., Meerovitch E. Pathogenicity of axenically cultivated Entamoeba histolytica, strain 200:NIH, in the hamster. J Parasitol. 1979 Oct;65(5):768–771. [PubMed] [Google Scholar]
  16. Gillin F. D., Diamond L. S. Entamoeba histolytica and Entamoeba invadens: effects of temperature and oxygen tension on growth and survival. Exp Parasitol. 1980 Jun;49(3):328–338. doi: 10.1016/0014-4894(80)90069-7. [DOI] [PubMed] [Google Scholar]
  17. Hassan H. M., Fridovich I. Regulation of the synthesis of superoxide dismutase in Escherichia coli. Induction by methyl viologen. J Biol Chem. 1977 Nov 10;252(21):7667–7672. [PubMed] [Google Scholar]
  18. Izhar M., Nuchamowitz Y., Mirelman D. Adherence of Shigella flexneri to guinea pig intestinal cells is mediated by a mucosal adhesion. Infect Immun. 1982 Mar;35(3):1110–1118. doi: 10.1128/iai.35.3.1110-1118.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kobiler D., Mirelman D. Adhesion of Entamoeba histolytica trophozoites to monolayers of human cells. J Infect Dis. 1981 Dec;144(6):539–546. doi: 10.1093/infdis/144.6.539. [DOI] [PubMed] [Google Scholar]
  20. Lo H., Reeves R. E. Purification and properties of NADPH:flavin oxidoreductase from Entamoeba histolytica. Mol Biochem Parasitol. 1980 Oct;2(1):23–30. doi: 10.1016/0166-6851(80)90045-6. [DOI] [PubMed] [Google Scholar]
  21. Lushbaugh W. B., Kairalla A. B., Cantey J. R., Hofbauer A. F., Pittman F. E. Isolation of a cytotoxin-enterotoxin from Entamoeba histolytica. J Infect Dis. 1979 Jan;139(1):9–17. doi: 10.1093/infdis/139.1.9. [DOI] [PubMed] [Google Scholar]
  22. Lushbaugh W. B., Kairalla A. B., Loadholt C. B., Pittman F. E. Effect of hamster liver passage on the virulence of axenically cultivated Entamoeba histolytica. Am J Trop Med Hyg. 1978 Mar;27(2 Pt 1):248–254. doi: 10.4269/ajtmh.1978.27.248. [DOI] [PubMed] [Google Scholar]
  23. Mattern C. F., Keister D. B., Natovitz P. C. Virulence of Entamoeba histolytica upon continuous axenic cultivation. Arch Invest Med (Mex) 1982;13 (Suppl 3):185–190. [PubMed] [Google Scholar]
  24. Mirelman D., Altmann G., Eshdat Y. Screening of bacterial isolates for mannose-specific lectin activity by agglutination of yeasts. J Clin Microbiol. 1980 Apr;11(4):328–331. doi: 10.1128/jcm.11.4.328-331.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mirelman D., Feingold C., Wexler A., Bracha R. Interactions between Entamoeba histolytica, bacteria and intestinal cells. Ciba Found Symp. 1983;99:2–30. doi: 10.1002/9780470720806.ch2. [DOI] [PubMed] [Google Scholar]
  26. Mirelman D., Yashouv-Gan Y., Schwarz U. Regulation of murein biosynthesis and septum formation in filamentous cells of Escherichia coli PAT 84. J Bacteriol. 1977 Mar;129(3):1593–1600. doi: 10.1128/jb.129.3.1593-1600.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Montalvo F. E., Reeves R. E., Warren L. G. Aerobic and anaerobic metabolism in Entamoeba histolytica. Exp Parasitol. 1971 Oct;30(2):249–256. doi: 10.1016/0014-4894(71)90089-0. [DOI] [PubMed] [Google Scholar]
  28. Morris J. G. Fifth Stenhous-Williams memorial lecture. Oxygen and the obligate anaerobe. J Appl Bacteriol. 1976 Jun;40(3):229–244. doi: 10.1111/j.1365-2672.1976.tb04171.x. [DOI] [PubMed] [Google Scholar]
  29. Murray H. W., Aley S. B., Scott W. A. Susceptibility of Entamoeba histolytica to oxygen intermediates. Mol Biochem Parasitol. 1981 Oct;3(6):381–391. doi: 10.1016/0166-6851(81)90038-4. [DOI] [PubMed] [Google Scholar]
  30. Muńoz M. L., Calderón J., Rojkind M. The collagenase of Entamoeba histolytica. J Exp Med. 1982 Jan 1;155(1):42–51. doi: 10.1084/jem.155.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Orozco E., Guarneros G., Martinez-Palomo A., Sánchez T. Entamoeba histolytica. Phagocytosis as a virulence factor. J Exp Med. 1983 Nov 1;158(5):1511–1521. doi: 10.1084/jem.158.5.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Orozco E., Martínez-Palomo A., Lopez-Revilla R. Un modelo in vitro para el estudio cuantitativo de la virulencia de E. histolytica. Arch Invest Med (Mex) 1978;9 (Suppl 1):257–260. [PubMed] [Google Scholar]
  33. PHILLIPS B. P., BARTGIS I. L. Effects of growth in vitro with selected microbial associates and of encystation and excystation, on the virulence of Endamoeba histolytica for guinea pigs. Am J Trop Med Hyg. 1954 Jul;3(4):621–627. doi: 10.4269/ajtmh.1954.3.621. [DOI] [PubMed] [Google Scholar]
  34. Phillips B. P. Entamoeba histolytica: concurrent irreversible loss of infectivity-pathogenicity and encystment potential after prolonged maintenance in axenic culture in vitro. Exp Parasitol. 1973 Oct;34(2):163–167. doi: 10.1016/0014-4894(73)90075-1. [DOI] [PubMed] [Google Scholar]
  35. Sargeaunt P. G., Jackson T. F., Simjee A. Biochemical homogeneity of Entamoeba histolytica isolates, especially those from liver abscess. Lancet. 1982 Jun 19;1(8286):1386–1388. doi: 10.1016/s0140-6736(82)92502-8. [DOI] [PubMed] [Google Scholar]
  36. Sargeaunt P. G., Williams J. E., Neal R. A. A comparative study of Entamoeba histolytica (NIH :200, HK9, etc.), "E. histolytica-like" and other morphologically identical amoebae using isoenzyme electrophoresis. Trans R Soc Trop Med Hyg. 1980;74(4):469–474. doi: 10.1016/0035-9203(80)90058-9. [DOI] [PubMed] [Google Scholar]
  37. Trissl D., Martínez-Palomo A., de la Torre M., de la Hoz R., Pérez de Suárez E. Surface properties of Entamoeba: increased rates of human erythrocyte phagocytosis in pathogenic strains. J Exp Med. 1978 Nov 1;148(5):1137–1143. doi: 10.1084/jem.148.5.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weinbach E. C., Diamond L. S. Entamoeba histolytica. I. Aerobic metabolism. Exp Parasitol. 1974 Apr;35(2):232–243. doi: 10.1016/0014-4894(74)90027-7. [DOI] [PubMed] [Google Scholar]
  39. Wittner M., Rosenbaum R. M. Role of bacteria in modifying virulence of Entamoeba histolytica. Studies of amebae from axenic cultures. Am J Trop Med Hyg. 1970 Sep;19(5):755–761. doi: 10.4269/ajtmh.1970.19.755. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES