Clin Microbiol Rev 13(2): 196-206

Cysteine Proteinases and the Pathogenesis of Amebiasis

Departments of Pathology and Medicine, University of California San Diego Medical Center, San Diego, California 92103-8416

^{Corresponding author. Mailing address: Division of Infectious Diseases, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8416. Phone: (619) 543-6146. Fax: (619) 543-6614. E-mail:}ude.dscu@deerls.

Abstract

Amebiasis is a major cause of morbidity and mortality throughout the tropical world. Entamoeba histolytica is now recognized as a separate species from the morphologically identical E. dispar, which cannot invade. Cysteine proteinases are a key virulence factor of E. histolytica and play a role in intestinal invasion by degrading the extracellular matrix and circumventing the host immune response through cleavage of secretory immunoglobulin A (sIgA), IgG, and activation of complement. Cysteine proteinases are encoded by at least seven genes, several of which are found in E. histolytica but not E. dispar. A number of new animal models, including the formation of liver abscesses in SCID mice and intestinal infection in human intestinal xenografts, have proven useful to confirm the critical role of cysteine proteinases in invasion. Detailed structural analysis of cysteine proteinases should provide further insights into their biochemical function and may facilitate the design of specific inhibitors which could be used as potential chemotherapeutic agents in the future.

Abstract

ACKNOWLEDGMENTS

This work was supported in part by grants from NIH (AI-28035 and DK-35108).

We thank Charles Davis for helpful discussions.

ACKNOWLEDGMENTS

REFERENCES

References

1. Abou-El-Magd I, Soon C G, El-Hawey A M, Ravdin J IHumoral and mucosal IgA antibody response to a recombinant 52-kDa cysteine-rich portion of the Entamoeba histolytica galactose-inhibitable lectin correlates with detection of native 170-kDa lectin antigen in serum of patients with amebic colitis. J Infect Dis. 1966;174:157–162.[PubMed][Google Scholar]
2. Acuna-Soto R, Samuelson J, De Girolami P, Zarate L, Millan-Velasco F, Schoolnick G, Wirth DApplication of the polymerase chain reaction to the epidemiology of pathogenic and nonpathogenic Entamoeba histolytica. Am J Trop Med Hyg. 1993;48:58–70.[PubMed][Google Scholar]
3. Allason-Jones E, Mindel A, Sargeaunt P G, Katz DOutcome of untreated infection with Entamoeba histolytica in homosexual men with and without HIV antibody. Br Med J. 1988;297:654–657.[Google Scholar]
4. Ankri S, Stolarsky T, Mirelman DAntisense inhibition of expression of cysteine proteinases does not affect Entamoeba histolytica cytopathic or haemolytic activity but inhibits phagocytosis. Mol Microbiol. 1998;28:777–785.[PubMed][Google Scholar]
5. Ankri S, Stolarsky T, Bracha R, Padilla-Vaca F, Mirelman DAntisense inhibition of expression of cysteine proteinases affects Entamoeba histolytica-induced formation of liver abscess in hamsters. Infect Immun. 1999;67:421–322.[Google Scholar]
6. Auriault C, Ouaissi M A, Torpier G, Eisen H, Capron AProteolytic cleavage of IgG bound to the Fc receptor of Schistosoma mansoni schistosomula. Parasite Immunol. 1981;3:33–44.[PubMed][Google Scholar]
7. Barrett A J, Kembhavi A A, Brown M A, Kirschke H, Knight C G, Tamai M, Hanada K1-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including Cathepsins B, H, and L. Biochem J. 1982;201:189–198.[Google Scholar]
8. Barrett A J, Kirschke HCathepsin B, cathepsin H, and cathepsin L. Methods Enzymol. 1981;80:535–561.[PubMed][Google Scholar]
9. Bontempi E, Cazzulo J JDigestion of human immunoglobulin G by the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. FEMS Microbiol Lett. 1990;70:337–342.[PubMed][Google Scholar]
10. Braga L, Ninomiya H, McCoy J J, Eacker S, Wiedmer T, Pham C, Wood S, Sims P J, Petri W AInhibition of the complement membrane attack complex by the galactose-specific adhesin of Entamoeba histolytica. J Clin Investig. 1992;90:1131–1137.[Google Scholar]
11. Bruchhaus I, Jacobs T, Leippe M, Tannich E. Entamoeba histolytica and Entamoeba dispar: differences in numbers and expression of cysteine proteinase genes. Mol Microbiol. 1996;22:255–263.[PubMed]
12. Bruchhaus I, Tannich EA gene highly homologous to ACP1 encoding cysteine proteinase 3 in Entamoeba histolytica is present and expressed in E. dispar. Parasitol Res. 1996;82:189–192.[PubMed][Google Scholar]
13. Calderon J, Schreiber R DActivation of the alternative and classical complement pathways by Entamoeba histolytica. Infect Immun. 1985;50:560–565.[Google Scholar]
14. Cao M, Chao H, Doughty B LA cDNA from Schistosoma mansoni eggs sharing sequence features of mammalian cystatin. Mol Biochem Parasitol. 1993;57:175–6.[PubMed][Google Scholar]
15. Carmona C, Dowd A J, Smith A M, Dalton J PCathepsin L proteinase secreted by Fasciola hepatica in vitro prevents antibody-mediated eosinophil attachment to newly excysted juveniles. Mol Biochem Parasitol. 1993;62:9–18.[PubMed][Google Scholar]
16. Carrero J C, Diaz M Y, Viveros M, Espinoza B, Acosta E, Ortiz-Ortiz LHuman secretory immunoglobulin A anti-Entamoeba histolytica antibodies inhibit adherence of amebae to MDCK cells. Infect Immun. 1994;62:764–767.[Google Scholar]
17. Chadee K, Meerovitch EThe pathogenesis of experimentally induced amebic liver abscess in the gerbil (Meriones unguiculatus) Am J Pathol. 1984;117:71–80.[Google Scholar]
18. Chadee K, Meerovitch EThe pathology of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus) Am J Pathol. 1985;119:485–494.[Google Scholar]
19. Chan S J, Segundo B S, McCormick M B, Steiner D FNucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs. Proc Natl Acad Sci USA. 1986;83:7721–7725.[Google Scholar]
20. Cieslak P R, Virgin H W, Stanley S LA severe combined immunodeficient (SCID) mouse model for infection with Entamoeba histolytica. J Exp Med. 1992;176:1605–1609.[Google Scholar]
21. Coulombe R, Grochulski P, Sivaraman J, Menard R, Mort J S, Cygler MStructure of human procathepsin L reveals the molecular basis of inhibition by the prosegment. EMBO J. 1996;15:5492–5503.[Google Scholar]
22. De Meester F, Shaw E, Scholze H, Stolarsky T, Mirelman DSpecific labeling of cysteine proteinases in pathogenic and nonpathogenic Entamoeba histolytica. Infect Immun. 1990;58:1396–1401.[Google Scholar]
23. Eakin A E, Mills A A, Harth G, McKerrow J H, Craik C SThe sequence, organization, and expression of the major cysteine proteinase (cruzain) from Trypanosoma cruzi. J Biol Chem. 1992;267:7411–7420.[PubMed][Google Scholar]
24. Engel J C, Doyle P S, Palmer J, Hsieh I, Bainton D F, McKerrow J HCysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci. 1998;111:597–606.[PubMed][Google Scholar]
25. Engel J C, Doyle P S, Hsieh I, McKerrow J HCysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med. 1998;188:725–734.[Google Scholar]
26. Espinosa M, Castanon G, Martinez-Palomo A. In vivo pathogenesis of Entamoeba dispar. Arch Investig Med. 1997;28:S204–S206.[PubMed]
27. Forney J R, Yang S, Healey M CProtease activity associated with excystation of Cryptosporidium parvum oocysts. J Parasitol. 1996;82:889–892.[PubMed][Google Scholar]
28. Franke de Cazzulo B M, Martinez J, North M, Coombs G H, Cazzulo J JEffects of proteinase inhibitors on the growth and differentiation of Trypanosoma cruzi. FEMS Microbiol Lett. 1994;124:81–86.[PubMed][Google Scholar]
29. Garcia-Rivera G, Rodriguez M A, Ocadiz R, Martinez-Lopez M C, Arroyo R, Gonzalez-Robles A, Orozco E. Entamoeba histolytica: a novel cysteine protease and an adhesin form the 112 kDa surface protein. Mol Microbiol. 1999;33:556–568.[PubMed]
30. Gathiram V, Jackson T F H GA longitudinal study of asymptomatic carriers of pathogenic zymodemes of Entamoeba histolytica. S Afr Med J. 1987;72:669–672.[PubMed][Google Scholar]
31. Genco R J, Plaut A G, Moellering R CEvaluation of human oral organisms and pathogenic Streptococcus for production of IgA protease. J Infect Dis. 1975;131(Suppl. 1):s17–s21.[PubMed][Google Scholar]
32. Ghosh S K, Field J, Frisardi M, Rosenthal B, Mia Z, Rogers R, Samuelson JChitinase secretion by encysting Entamoeba invadens and transfected Entamoeba histolytica trophozoites: localization of secretory vesicles, endoplasmic reticulum, and Golgi apparatus. Infect Immun. 1999;67:3073–3081.[Google Scholar]
33. Griffiths G, Hoflack B, Simmons K, Mellman I, Kornfeld SThe mannose 6-phosphate receptor and the biogenesis of lysosomes. Cell. 1988;52:329–341.[PubMed][Google Scholar]
34. Grundy M S, Cartwright-Taylor L, Lundin LAntibodies against Entamoeba histolytica in human milk and serum in Kenya. J Clin Microbiol. 1983;17:753–758.[Google Scholar]
35. Hamelmann C, Foerster B, Burchard G D, Horstmann R DLysis of pathogenic and nonpathogenic Entamoeba histolytica by human complement: methodological analysis. Parasite Immunol. 1992;14:23–35.[PubMed][Google Scholar]
36. Haque R, Neville L, Hahn P, Petri W ARapid diagnosis of Entamoeba infection by using Entamoeba and Entamoeba histolytica stool antigen detection kits. J Clin Microbiol. 1995;33:2558–2561.[Google Scholar]
37. Haque R, Ali I K M, Akther S, Petri W AComparison of PCR, isoenzyme analysis, and antigen detection for diagnosis of Entamoeba histolytica infection. J Clin Microbiol. 1998;36:449–452.[Google Scholar]
38. Harth G, Andrews N, Mills A A, Engel J C, Smith R, McKerrow J HPeptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol Biochem Parasitol. 1993;58:17–24.[PubMed][Google Scholar]
39. Huete-Perez J A, Engel J C, Brinen L S, Mottram J C, McKerrow J HProtease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif. J Biol Chem. 1999;274:16249–16256.[PubMed][Google Scholar]
40. Hugli T EBiochemistry and biology of anaphylatoxins. Complement. 1986;3:111–127.[PubMed][Google Scholar]
41. Irvine J W, Coombs G H, North M JCystatin-like cysteine proteinase inhibitors of parasitic protozoa. FEMS Microbiol Lett. 1992;75:67–72.[PubMed][Google Scholar]
42. Jackson T F H G, Gathiram V, Simjee A ESeroepidemiological study of antibody responses to the zymodemes of Entamoeba histolytica. Lancet. 1985;ii:716–719.[PubMed][Google Scholar]
43. Jacobs T, Bruchhaus I, Dandekar T, Tannich E, Leippe MIsolation and molecular characterization of a surface-bound proteinase of Entamoeba histolytica. Mol Microbiol. 1998;27:269–276.[PubMed][Google Scholar]
44. Karrer K M, Peiffer S L, DiTomas M ETwo distinct gene subfamilies within the family of cystiene proteinase genes. Proc Natl Acad Sci USA. 1993;90:3063–3067.[Google Scholar]
45. Keene W E, Hidalgo M E, Orozco E, McKerrow J H. Entamoeba histolytica: correlation of the cytopathic effect of virulent trophozoites with secretion of a cysteine proteinase. Exp Parasitol. 1990;71:199–206.[PubMed]
46. Keene W E, Pettit M G, Allen S, McKerrow J HThe major neutral proteinase of Entamoeba histolytica. J Exp Med. 1986;163:536–549.[Google Scholar]
47. Kelsall B L, Ravdin J IDegradation of human immunoglobulin A by Entamoeba histolytica. J Infect Dis. 1993;168:1319–1322.[PubMed][Google Scholar]
48. Kilian M, Mestecky J, Russell M WDefense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial Immunoglobulin A proteases. Microbiol Rev. 1988;52:296–303.[Google Scholar]
49. Kilian M, Mestecky J, Kulhavy R, Tomana M, Butler W TIgA1 proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Streptococcus sanguis: comparative immunochemical studies. J Immunol. 1980;124:2596–2600.[PubMed][Google Scholar]
50. Kornfeld S J, Plaut A GSecretory immunity and the bacterial IgA proteases. Rev Infect Dis. 1981;3:521–534.[PubMed][Google Scholar]
51. Leippe M, Sebastian E, Schoenberger O L, Horstmann R D, Muller-Eberhard H JPore-forming peptide of pathogenic Entamoeba histolytica. Proc Natl Acad Sci USA. 1991;88:7659–7663.[Google Scholar]
52. Leon G, Fiori C, Das P, Moreno M, Tovar R, Sanchez-Salas J L, de Lourdes Munoz MElectron probe analysis and biochemical characterization of electron-dense granules secreted by Entamoeba histolytica. Mol Biochem Parasitol. 1997;85:223–242.[PubMed][Google Scholar]
53. Levya O, Rico G, Ramos F, Moran P, Melendro E I, Ximenez C Entamoeba histolytica adherence: inhibition by IgA monoclonal antibodies. In: Mestecky J, editor. Advances in mucosal immunology. New York, N.Y: Plenum Press; 1995. pp. 681–683. [[PubMed][Google Scholar]
54. Li E, Yang W-G, Zhang T, Stanley S LInteraction of laminin with Entamoeba histolytica cysteine proteinases and its effect on amebic pathogenesis. Infect Immun. 1995;63:4150–4153.[Google Scholar]
55. Long-Krug S A, Fischer K J, Hysmith R M, Ravdin J IPhospholipase A enzymes of Entamoeba histolytica: description and subcellular localization. J Infect Dis. 1985;152:536–541.[PubMed][Google Scholar]
56. Luaces A L, Barrett A JAffinity purification and biochemical characterization of histolysin, the major cysteine proteinase of Entamoeba histolytica. Biochem J. 1988;250:903–909.[Google Scholar]
57. Mahajan R C, Agarwal S C, Chhuttani P N, Chitkara N LCoproantibodies in intestinal amoebiasis. Ind J Med Res. 1972;60:547–550.[PubMed][Google Scholar]
58. Maubach G, Schilling K, Rommerskirch W, Wenz I, Schultz J E, Weber E, Wiederanders BThe inhibition of cathepsin S by its propeptide-specificity and mechanism of action. Eur J Biochem. 1997;250:745–750.[PubMed][Google Scholar]
59. Mayer R, Picard I, Lawton P, Grellier P, Barrault C, Monsigny M, and Schrevel JPeptide derivatives specific for a Plasmodium falciparum proteinase inhibit the human erythrocyte invasion by merozoites. J Med Chem. 1991;34:3029–3035.[PubMed][Google Scholar]
60. Mazzuco A, Benchimol M, DeSouza WEndoplasmic reticulum and Golgi-like elements in Entamoeba.Micron. 1997;28:241–247.[PubMed][Google Scholar]
61. McIntyre G F, Godbold G D, Erickson A HThe pH-dependent membrane association of procathepsin L is mediated by a 9-residue sequence within the propeptide. J Biol Chem. 1994;269:567–572.[PubMed][Google Scholar]
62. Mirelman D, Nucharnowitz Y, Bohm G B, Walderich BA homologue of the cysteine proteinase gene (ACP1 or Eh-CPp3) of pathogenic Entamoeba histolytica is present in non-pathogenic E. dispar strains. Mol Biochem Parasitol. 1996;78:47–54.[PubMed][Google Scholar]
63. Mort J S, Leduc M S, Recklies A DCharacterization of a latent cysteine proteinase from ascitic fluid as a high molecular weight form of cathepsin B. Biochim Biophys Acta. 1983;755:369–375.[PubMed][Google Scholar]
64. Mort J S, Leduc M, Recklies A DA latent thiol proteinase from ascitic fluid of patients with neoplasia. Biochim Biophys Acta. 1981;662:173–180.[PubMed][Google Scholar]
65. Munoz M, Lamoyi E, Leon G, Tovar R, Perez-Garcia J, de la Torre M, Murueta E, Bernal R MAntigens in electron-dense granules from Entamoeba histolytica as possible markers for pathogenicity. J Clin Microbiol. 1990;2418:2424.[Google Scholar]
66. Navarro-Garcia F, Chavez-Duenas L, Tsutsumi V, Posadas del Rio F, Lopez-Revilla R. Entamoeba histolytica: increase of enterotoxicity and of 53- and 75-kDa cysteine proteinases in a clone of higher virulence. Exp Parasitol. 1995;80:361–372.[PubMed]
67. Orozco E, Guarneros G, Martinez-Palomo A, Sanchez T. Entamoeba histolytica phagocytosis as a virulence factor. J Exp Med. 1983;158:1511–1521.
68. Pamer E G, So M, Davis C EIdentification of a developmentally regulated cysteine protease of Trypanosoma brucei.Mol Biochem Parasitol. 1989;33:27–32.[PubMed][Google Scholar]
69. Perez-Tamayo R, Martinez R D, Montfort I, Becker I, Tello E, Perez-Montfort RPathogenesis of acute experimental amebic liver abscess in hamsters. J Parasitol. 1991;77:982–988.[PubMed][Google Scholar]
70. Petri W A, Smith R D, Schlesinger P H, Murphy C F, Ravdin J IIsolation of the galactose-binding lectin that mediates the in vitro adherence of Entamoeba histolytica. J Clin Investig. 1987;80:1238–1244.[Google Scholar]
71. Petri W A, Ravdin J IProtection of gerbils from amebic liver abscess by immunization with the galactose-specific adherence lectin of Entamoeba histolytica. Infect Immun. 1990;59:97–101.[Google Scholar]
72. Petri W A, Singh UDiagnosis and management of amebiasis. Clin Infect Dis. 1999;29:11117–11125.[PubMed][Google Scholar]
73. Plaut A GThe IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol. 1983;37:603–622.[PubMed][Google Scholar]
74. Provenzano D, Alderete J FAnalysis of human immunoglobulin-degrading cysteine proteinases of Trichomonas vaginalis. Infect Immun. 1995;63:3388–3395.[Google Scholar]
75. Que X, Reed S LThe role of extracellular cysteine proteinases in pathogenesis of Entamoeba histolytica invasion. Parasitol Today. 1997;13:190–194.[PubMed][Google Scholar]
76. Quezada-Calvillo R, Lopez-Revilla RIgA protease in Entamoeba histolytica trophozoites. Adv Exp Med Biol. 1986;216B:1283–1288.[PubMed][Google Scholar]
77. Ramos F, Valenzuela O, Moran P, Gonzalez E, Ramiro M, Cedillo R, Martinez M, Gomez A, Munoz O, Melendro E, Ximenez CAnti-E. histolytica IgA antibodies in saliva of E. histolytica or E. dispar infected individuals: longitudinal study of cohorts. Arch Med Res. 1997;28:S327–S329.[PubMed][Google Scholar]
78. Ramos M A, Stock R P, Sanchez-Lopez, Rosana O, Felipe L, Paul A, and Alejandro MThe Entamoeba histolytica proteosome α-subunit gene. Mol Biochem Parasitol. 1997;84:131–135.[PubMed][Google Scholar]
79. Ravdin J I, Schlesinger P H, Murphy C F, Gluzman I Y, Krogstad D JAcid intracellular vesicles and the cytolysis of mammalian target cells by Entamoeba histolytica trophozoites. J Protozool. 1986;33:478–486.[PubMed][Google Scholar]
80. Ravdin J IAmebiasis. Clin Infect Dis. 1995;20:1453–1464.[PubMed][Google Scholar]
81. Recklies A D, Mort J SCharacterization of a cysteine proteinase secreted by mouse mammary gland. Cancer Res. 1985;45:2302–2307.[PubMed][Google Scholar]
82. Reed S L, Curd J G, Gigli I, Gillin F D, Braude A IActivation of complement by pathogenic and nonpathogenic Entamoeba histolytica. J Immunol. 1986;136:2265–2270.[PubMed][Google Scholar]
83. Reed S LAmebiasis: an update. Clin Infect Dis. 1992;14:385–393.[PubMed][Google Scholar]
84. Reed S LNew concepts regarding the pathogenesis of amebiasis. Clin Infect Dis. 1995;2(Suppl. 2):S182–S185.[PubMed][Google Scholar]
85. Reed S L, Keene W E, McKerrow J H, Gigli ICleavage of C3 by a neutral cysteine proteinase of Entamoeba histolytica. J Immunol. 1989;143:189–195.[PubMed][Google Scholar]
86. Reed S L, Bouvier J, Pollack A S, Engel J C, Brown M, Hirata K, Que X, Eakin A, Hagblom P, Gillin F D, McKerrow J HCloning of a virulence factor of Entamoeba histolytica: pathogenic strains possess a unique cysteine proteinase gene. J Clin Investig. 1993;91:1532–1540.[Google Scholar]
87. Reed S L, Wessel D W, Davis C E. Entamoeba histolytica infection and AIDS. Am J Med. 1991;90:269–270.[PubMed]
88. Reed S L, Ember J A, Herdman D S, DiScipio R G, Hugli T E, Gigli IThe extracellular neutral cysteine proteinase of Entamoeba histolytica degrades anaphylatoxins C3a and C5a. J Immunol. 1995;155:266–274.[PubMed][Google Scholar]
89. Reed S L, Gigli ILysis of complement-sensitive Entamoeba histolytica by activated terminal complement components. Initiation of complement activation by an extracellular neutral cysteine proteinase. J Clin Investig. 1990;86:1815–1822.[Google Scholar]
90. Reed S L, Flores B M, Batzer M A, Stein M A, Stroeher V L, Carlton J E, Diedrich D L, Torian B EMolecular and cellular characterization of the 29-kDa peripheral membrane protein of Entamoeba histolytica: differentiation between pathogenic and nonpathogenic isolates. Infect Immun. 1992;60:542–549.[Google Scholar]
91. Reed S L, Keene W E, McKerrow J HThiol proteinase expression correlates with pathogenicity of Entamoeba histolytica. J Clin Microbiol. 1989;27:2772–2777.[Google Scholar]
92. Robertson C D, Coombs G H, North M J, Mottram J CParasite cysteine proteinases. Perspect Drug Discov Des. 1996;6:99–118.[PubMed][Google Scholar]
93. Roche L, Tort J, Dalton J PThe propeptide of Fasciola hepatica cathepsin L is a potent and selective inhibitor of the mature enzyme. Mol Biochem Parasitol. 1999;98:271–277.[PubMed][Google Scholar]
94. Rosenthal P J, McKerrow J H, Aikawa M, Nagasawa H, Leech J HA malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J Clin Investig. 1988;82:1560–1566.[Google Scholar]
95. Rosenthal P JProteases of protozoan parasites. Adv Parasitol. 1999;43:106–139.[PubMed][Google Scholar]
96. Rozhin J, Robinson D, Stevens M A, Lah T T, Honn K V, Ryan R E, Sloane B FProperties of a plasma membrane-associated cathepsin B-like cysteine proteinase in metastatic B16 melanoma variants. Cancer Res. 1987;47:6620–6628.[PubMed][Google Scholar]
97. Salas F, Fichmann J, Lee G K, Scott M D, Rosenthal P JFunctional expression of falcipain, a Plasmodium falciparum cysteine proteinase, supports its role as a malarial hemoglobinase. Infect Immun. 1995;63:2120–2125.[Google Scholar]
98. Sanchez-Lopez R, Gama-Castro S, Ramos M A, Merino E, Lizardi P M, Alagon ACloning and expression of the Entamoeba histolytica ERD2 gene. Mol Biochem Parasitol. 1998;92:355–359.[PubMed][Google Scholar]
99. Sargeaunt P G, Williams J E, Greene J DThe differentiation of invasive and noninvasive Entamoeba histolytica by isoenzyme electrophoresis. Trans R Soc Trop Med Hyg. 1978;72:519–521.[PubMed][Google Scholar]
100. Scheidt K A, Roush W R, McKerrow J H, Selzer P M, Hansell E, Rosenthal P JStructure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem. 1998;6:2477–2494.[PubMed][Google Scholar]
101. Scholze H, Schulte WOn the specificity of a cysteine proteinase from Entamoeba histolytica. Biomed Biochim Acta. 1988;47:115–123.[PubMed][Google Scholar]
102. Scholze H, Lohden-Bendinger U, Muller G, Bakker-Grunwald TSubcellular distribution of amebapain, the major cysteine proteinase of Entamoeba histolytica. Arch Med Res. 1992;23:105–108.[PubMed][Google Scholar]
103. Scholze H, Frey S, Cejka Z, Bakker-Grunwald TEvidence for the existence of both proteasomes and a novel high molecular weight peptidase in Entamoeba histolytica. J Biol Chem. 1996;271:6212–6216.[PubMed][Google Scholar]
104. Selzer P M, Chen X, Chan V J, Cheng M, Kenyon G L, Kuntz I D, Sakanari J A, Cohen F E, McKerrow J H. Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors. Exp Parasitol. 1997;87:212–221.[PubMed]
105. Serrano J J, de la Garza M, Moreno M A, Tovar R, Leon G, Tsutsumi V, de Lourdes Munoz M. Entamoeba histolytica: electron-dense granule secretion, collagenase activity and virulence are altered in the cytoskeleton mutant BG-3. Mol Microbiol. 1994;11:787–792.[PubMed]
106. Seydel K B, Li E, Swanson P E, Stanley S LHuman intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis. Infect Immun. 1997;65:1631–1639.[Google Scholar]
107. Sharma M, Hirata K, Herdman S, Reed S. Entamoeba invadens: characterization of cysteine proteinases. Exp Parasitol. 1996;84:84–91.[PubMed]
108. Sharma P, Das P, Dutta G PUse of glutaraldehyde-treated sheep erythrocytes in indirect haemagglutination test for amoebic coproantibody. Indian J Med Res. 1981;74:215–218.[PubMed][Google Scholar]
109. Shibayama M, Navarro-Garcia F, Lopez-Revilla R, Martinez-Palomo A, Tsutumi VIn vivo and in vitro experimental intestinal amebiasis in Mongolian gerbils (Meriones unguiculatus) Parasitol Res. 1997;83:170–176.[PubMed][Google Scholar]
110. Sloane B F, Moin K, Krepela E, Rozhin JCathepsin B and its endogenous inhibitors: the role in tumor malignancy. Cancer Metastasis Rev. 1990;9:333–352.[PubMed][Google Scholar]
111. Sloane B F, Rozhin J, Johnson K, Taylor H, Crissman J D, Honn K VCathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci USA. 1986;83:2483–2487.[Google Scholar]
112. Sloane B F, Dunn J R, Honn K VLysosomal cathepsin B: correlation with metastatic potential. Science. 1981;212:1151–1153.[PubMed][Google Scholar]
113. Smith S M, Gottesman M MActivity and deletion analysis of recombinant human cathepsin L expressed in Escherichia coli. J Biol Chem. 1989;264:20487–20495.[PubMed][Google Scholar]
114. Soong C G, Torian B E, Abd-Alla M D, Jackson T F H G, Gatharim V, Ravdin J IProtection of gerbils from amebic liver abscess by immunization with recombinant Entamoeba histolytica 29-kilodalton antigen. Infect Immun. 1995;63:472–377.[Google Scholar]
115. Stanley S L, Zhang T, Rubin D, Li ERole of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice. Infect Immun. 1995;63:1587–1589.[Google Scholar]
116. Stanley S LProgress towards development of a vaccine for amebiasis. Clin Microbiol Rev. 1997;10:637–649.[Google Scholar]
117. Strachan W D, Spice W M, Chiodini P L, Moody A H, Ackers J PImmunological differentiation of pathogenic and non-pathogenic isolates of Entamoeba histolytica. Lancet. 1988;ii:561–563.[PubMed][Google Scholar]
118. Tachibana H, Ihara S, Kobayashi S, Kaneda Y, Takeuchi T, Watanabe YDifferences in genomic DNA sequences between pathogenic and nonpathogenic isolates of Entamoeba histolytica identified by polymerase chain reaction. J Clin Microbiol. 1991;29:2234–2239.[Google Scholar]
119. Tack B F, Janatova J, Thomas M L, Harrison R A, Hammer C HThe third, fourth, and fifth components of human complement: isolation and biochemical properties. Methods Enzymol. 1981;80:64–101.[PubMed][Google Scholar]
120. Takeuchi A, Phillips B PElectron microscope studies of experimental Entamoeba histolytica infections in the guinea pig. I. Penetration of the intestinal epithelium by trophozoites. Am J Trop Med Hyg. 1975;24:34–48.[PubMed][Google Scholar]
121. Talamas-Rohana P, Meza IInteraction between pathogenic amebas and fibronectin: substrate degradation and changes in cytoskeleton organization. J Cell Biol. 1988;106:1787–1794.[Google Scholar]
122. Talbot J A, Nielsen K, Corbeil L BCleavage of proteins of reproductive secretions by extracellular proteinases of Tritrichomonas foetus. Can J Microbiol. 1991;37:384–390.[PubMed][Google Scholar]
123. Taylor M A, Baker K C, Briggs G S, Connerton I F, Cummings N J, Pratt K A, Revell D F, Freedman R B, Goodenough P TRecombinant pro-regions from papain and papaya proteinase IV are selective high affinity inhibitors of the mature papaya enzymes. Protein Eng. 1995;8:59–62.[PubMed][Google Scholar]
124. Tran V Q, Herdman D S, Torian B E, Reed S LThe neutral cysteine proteinase of Entamoeba histolytica degrades IgG and prevents its binding. J Infect Dis. 1998;177:508–511.[PubMed][Google Scholar]
125. Underdown B J, Schiff J MImmunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol. 1986;4:389–417.[PubMed][Google Scholar]
126. Vazquez J, Franco E, Reyes G, Meza ICharacterization of adhesion plates induced by the interaction of Entamoeba histolytica trophozoites with fibronectin. Cell Motil Cytoskeleton. 1995;32:37–45.[PubMed][Google Scholar]
127. von Heijne GA new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986;14:4683–4690.[Google Scholar]
128. Walsh J A Prevelence of Entamoeba histolytica infection. In: Ravdin J I, editor. Amebiasis. Human infection by Entamoeba histolytica. New York, N.Y: John Wiley & Sons, Inc.; 1988. pp. 93–105. [PubMed]
129. Ward W, Alvarado L, Rawlings N D, Engel J C, Franklin C, McKerrow J HA primitive enzyme for a primitive cell: the protease required for excystation of Giardia. Cell. 1997;89:1–8.[PubMed][Google Scholar]
130. World Health Organization/Pan America Health Organization Expert Consultation on AmoebiasisAmoebiasis. W H O Weekly Epidem Rec. 1997;72:97–100.[PubMed][Google Scholar]
131. Zhang T, Cieslak P R, Stanley S LProtection of gerbils from amebic liver abscess by immunization with a recombinant Entamoeba histolytica antigen. Infect Immun. 1994;62:1166–1170.[Google Scholar]