A review of entamoebahistolytica genome, virulence factors, phylogenetic tree and treatment

  • Hind Abdulzahra Abdulkadhim Alshaibani Department of Biology, College of Education, University of Al-Qadisiyah, Iraq


The study in this review aims to know and study the parasite Entamoebahistolytica that causes Amoebiasis worldwide. During its life cycle, E. histolytica passes through several phases, trophozoite stage, precyst stage, the cyst stage, the Metacyst stage, and Metacystictrophozoite stage. In this study, the spread of the parasite globally and in the Arab world and methods of treating the disease were also discussed. The Genomic structureof E. histolytica, like other organisms, is characterized by diversity and heterogeneity in its genetic content, which is one of the most important reasons for its survival and its ability to infect. Interestingly, the genome of the E. histolytica contains a large amount of genes presumed to be of bacterial origin. The study of the genetic diversity of E. histolytica gives paths to the developmental change that resulted in the emergence of evolutionary features or traits. Understanding amoebic virulence is important. Several studies have shown that genetic factors influence the virulence of parasitic infections. Studying the virulence of E. histolytica by Serine-rich protein (REHP) gene is among the important issues used in molecular epidemiological studies.

Keywords: E. histolytica, Virulence factors, Phylogenetic tree, Genotypic diversity of E. Histolytica


Download data is not yet available.

Author Biography

Hind Abdulzahra Abdulkadhim Alshaibani, Department of Biology, College of Education, University of Al-Qadisiyah, Iraq

Department of Biology, College of Education, University of Al-Qadisiyah, Iraq


1. El-Dib, N.A., Entamoeba histolytica: an overview. Current Tropical Medicine Reports, 2017. 4(1): p. 11-20.
2. Gunn, A. and S.J. Pitt, Parasitology: an integrated approach. 2012: John Wiley & Sons.
3. Wells, C.D. and M. Arguedas, Amebic liver abscess. Southern medical journal, 2004. 97(7): p. 673-682.
4. Bogitsh, B.J., C.E. Carter, and T.N. Oeltmann, Human parasitology. 2013: Academic Press.
5. Clark, C.G., et al., Structure and Content of the Entamoeba histolytica Genome. Advances in parasitology, 2007. 65: p. 51-190.
6. Lohia, A., The cell cycle of Entamoeba histolytica. Molecular and cellular biochemistry, 2003. 253(1-2): p. 217-222.
7. Tanyuksel, M., et al., Comparison of two methods (microscopy and enzyme-linked immunosorbent assay) for the diagnosis of amebiasis. Experimental parasitology, 2005. 110(3): p. 322-326.
8. Barron-Gonzalez, M.P., et al., Entamoeba histolytica : Cyst-like structures in vitro induction. Experimental parasitology, 2008. 118(4): p. 600-603.
9. Arredondo, J.L., et al., Entamoeba histolytica: trophozoite, precyst and cyst studied by atomic force microscopy. 2014.
10. Krishnan, D. and S.K. Ghosh, Cellular events of multinucleated giant cells formation during the encystation of Entamoeba invadens. Frontiers in cellular and infection microbiology, 2018. 8: p. 262.
11. Mitra, B.N., et al., Compounds of the upper gastrointestinal tract induce rapid and efficient excystation of Entamoeba invadens. International Journal for Parasitology, 2010. 40: p. 9.
12. Tanyuksel, M. and W.A. Petri, Laboratory diagnosis of amebiasis. Clinical microbiology reviews, 2003. 16(4): p. 713-729.
13. Mitra, B.N., et al., Compounds of the upper gastrointestinal tract induce rapid and efficient excystation of Entamoeba invadens. International Journal forParasitology, 2009. 40(6): p. 751-760.
14. Bruckner, D.A., Amebiasis. Clinical microbiology reviews, 1992. 5(4): p. 356-69.
15. Pritt, B.S. and C.G. Clark. Amebiasis. in Mayo Clinic Proceedings. 2008. Elsevier.
16. Graham Clark, C., The evolution of Entamoeba, a cautionary tale. Research in microbiology, 2000. 151(8): p. 599-603.
17. Coppi, A. and D. Eichinger, Regulation of Entamoeba invadens encystation and gene expression with galactose and -N-acetylglucosamine. Molecular and biochemical parasitology, 1999. 102(1): p. 67-77.
18. Lopez-Romero, E. and J.C. Villagomez-Castro, Encystation in Entamoeba invadens. Parasitology Today, 1993. 9(6): p. 225-227.
19. Troll, H., H. Marti, and N.J.J.o.C.M. Weiss, Simple Differential Detection of Entamoeba histolyticaand Entamoeba dispar in Fresh Stool Specimens by Sodium Acetate-Acetic Acid-Formalin Concentration and PCR. 2000. 38(12): p. 4685-4685.
20. Mvjak, P., et al., Molecular differentiation of Entamoeba histolytica and Entamoeba dispar from stool and culturesamples obtained from polish citizens infected in tropics and in Poland. 2000. 39(3): p. 217-224.
21. Gonin, P. and L.J.J.o.c.m. Trudel, Detection and differentiation of Entamoeba histolytica and Entamoeba dispar isolates in clinical samples by PCR and enzyme-linked immunosorbent assay. 2003. 41(1): p. 237-241.
22. Sandra, M., et al., Determination of the prevalence of Entamoeba histolytica and E. dispar in the Pernambuco state of northeastern Brazil by a polymerase chain reaction. 2004. 70(2): p. 221-224.
23. 2van Doorn, H.R., et al., Use of rapid dipstick and latex agglutination tests and enzyme-linked immunosorbent assay for serodiagnosis of amebic liver abscess, amebic colitis, and Entamoeba histolytica cyst passage. 2005. 43(9): p. 4801-4806.
24. Samie, A., et al., Prevalence and species distribution of E. Histolytica and E. Dispar in the Venda region, Limpopo, South Africa. 2006. 75(3): p. 565-571.
Al-Nakkas, E.M., et al., Parasitic infections in Kuwait: A study based on Primary Care Centers. 2004. 3(3).
25. Youssef, M., et al., Bacterial, viral and parasitic enteric pathogens associated with acute diarrhea in hospitalized children from northern Jordan. 2000. 28(3): p. 257-263.
26. Stauffer, W., M. Abd-Alla, and J.I.J.A.o.m.r. Ravdin, Prevalenceand incidence of Entamoeba histolytica infection in South Africa and Egypt. 2006. 37(2): p. 265-268.
27. Al-Harthi, S.A. and M.J.W.J.M.S. Jamjoom, Diagnosis and differentiation of Entamoeba infection in Makkah Al Mukarramah using microscopy and stool antigen detection kits. 2007. 2(1): p. 15-20.
28. Al-Shaheen, Z., A. Al-Maki, and K.J.B.J.o.V.R. Hussien, A study on Prevalence of Entamoeba histolytica and Giardia lamblia infection among patient attending Quarna Hospital in Basra. 2007. 6(2): p. 30-36.
29. Del Rocío Villalobos-Gómez, F., et al., Entamoeba histolytica L220 induces the in vitro activation of macrophages and neutrophils and is modulated by neurotransmitters. Acta parasitologica, 2018. 63(2): p. 270-279.
30. Islam, B. and A.U. Khan, Lectins: Tocombat infections. Protein Purification, 2012. 1: p. 167-188.
31. Bailey, G.B., J.R. Gilmour, and N.E. McCoomer, Roles of target cell membrane carbohydrate and lipid in Entamoeba histolytica interaction with mammalian cells. Infection and immunity, 1990. 58(7): p. 2389-2391.
32. Braga, L.L., et al., Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica. Journal of Clinical Investigation, 1992. 90(3): p. 1131-1137.
33. Houpt, E., et al., Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin. Vaccine, 2004. 22(5): p. 611-617.
34. Ravdin, J.I. and R.L. Guerrant, Role of adherence in cytopathogenic mechanisms of Entamoeba histolytica: study with mammaliantissue culture cells and human erythrocytes. Journal of Clinical Investigation, 1981. 68(5): p. 1305 - 1313.
35. Saffer, L.D. and W.A. Petri, Role of the galactose lectin of Entamoeba histolytica in adherence-dependent killing of mammalian cells. Infection and immunity, 1991. 59(12): p. 4681-4683.
36. Petri Jr, W.A., R. Haque, and B.J. Mann, The bittersweet interface of parasite and host: lectin-carbohydrate interactions during human invasion by the parasite Entamoeba histolytica. Annual Reviews in Microbiology, 2002. 56(1): p. 39-64.
37. Leckenby, A., Improved genomic assembly and genomic analyses of Entamoeba histolytica. 2018: The University of Liverpool (United Kingdom).
38. Tillack, M., et al., Increased expression of the major cysteine proteinases by stable episomal transfection underlines the important role of EhCP5 for the pathogenicity of Entamoeba histolytica. Molecular and biochemical parasitology, 2006. 149(1): p. 58-64.
39. Montfort, I., A. Olivos, and R. Pirez-Tamayo, Phagocytosis and proteinase activity are not related to pathogenicity ofE. histolytica. Parasitology research, 1993. 79(2): p. 160-162.
40. McLaughlin, J. and G. Faubert, Partial purification and some properties of a neutral sulfhydryl and an acid proteinase from Entamoeba histolytica. Canadian Journal of Microbiology, 1977. 23(4): p. 420-425.
41. Lushbaugh, W.B., A.F. Hofbauer, and F.E. Pittman, Proteinase activities of Entamoeba histolytica cytotoxin. GastroenterologY., 1984. 87(1): p. 17-27.
42. Lushbaugh, W.B., A.F. Hofbauer, and F.E. Pittman, Entamoeba histolytica: purification of cathepsin B. Experimental parasitology, 1985. 59(3): p. 328-336.
43. Keene, W.E., et al., Entamoeba histolytica: correlation of the cytopathic effect of virulent trophozoites with secretion of acysteine proteinase. Experimental parasitology, 1990. 71(2): p. 199-206.
44. Luaces, A.L. and A.J. Barrett, Affinity purification and biochemical characterization of histolysin, the major cysteine proteinase of Entamoeba histolytica. Biochem. J, 1988. 250: p. 903-909.
45. Luaces, A.L., T. Pico, and A.J. Barrett, The ENZYMEBA test: detection of intestinal Entamoeba histolytica infection by immuno-enzymatic detection of histolysain. Parasitology, 1992. 105(02): p. 203-205.
46. Scholze, H., et al., Subcellular distribution of amebapain, the major cysteine proteinase of Entamoeba histolytica. Archives of medical research, 1991. 23(2): p. 105-108.
47. Leippe, M., et al., Spontaneous release of cysteine proteinases but not of pore-forming peptides by viable Entamoeba histolytica. Parasitology, 1995. 111(05): p. 569-574.
48. Garcia-Rivera, G., et al., Entamoeba histolytica: a novel cysteine protease and an adhesin form the 112 kDa surface protein. Molecular microbiology, 1999. 33(3): p. 556-568.
49. Jacobs, T., et al., Isolation and molecular characterization of a surfaceâ-bound proteinase of Entamoeba histolytica. Molecular microbiology, 1998. 27(2): p. 269-276.
50. Bruchhaus, I., et al., The intestinal protozoan parasite Entamoeba histolytica contains 20 cysteine protease genes, of which only a small subset is expressed during in vitro cultivation. Eukaryotic cell, 2003. 2(3): p. 501-509.
51. Barrett, A.J., Cysteine peptidase, pp. 543-798. In A. J. Barrett, N. D. Rawlings, and J. F. Woessner (Eds). Handbook of proteolytic enzymes, Academic Press, Inc.,, San Diego, Calif. 1998.
52. Keene, W.E., et al., The major neutral proteinase of Entamoeba histolytica. The Journal of experimental medicine, 1986. 163(3): p. 536-549.
53. Reed, S.L. and I. Gigli, Lysis of complement-sensitive Entamoeba histolytica by activated terminal complement components. Initiation of complement activation by an extracellular neutral cysteine proteinase. Journal of Clinical Investigation, 1990. 86(6): p. 1815 - 1822.
54. Kelsall, B.L. andJ.I. Ravdin, Degradation of human IgA by Entamoeba histolytica. Journal of Infectious Diseases, 1993. 168(5): p. 1319-1322.
55. Tran, V.Q., et al., The neutral cysteine proteinase of Entamoeba histolyticadegrades IgG and prevents its binding. Journal ofInfectious Diseases, 1998. 177(2): p. 508-511.
56. Andrä, J., R. Herbst, and M. Leippe, Amoebapores, archaic effector peptides of protozoan origin, are discharged into phagosomes and kill bacteria by permeabilizing their membranes. Developmental & Comparative Immunology, 2003. 27(4): p. 291-304.
57. Hecht, O., et al., Solution structure of the pore-forming protein of Entamoeba histolytica. Journal of Biological Chemistry, 2004. 279(17): p. 17834-17841.
58. Leippe, M., et al., Ancient weapons: the three-dimensional structure of amoebapore A. Trends in parasitology, 2005. 21(1): p. 5-7.
59. Bruhn, H., et al., Amoebapores and NK-lysin, members of a class of structurally distinct antimicrobial and cytolytic peptides from protozoa and mammals: a comparative functional analysis. Biochem. J, 2003. 375: p. 737-744.
60. Gutsmann, T., et al., Interaction of amoebapores and NK-lysin with symmetric phospholipid and asymmetric lipopolysaccharide/phospholipid bilayers. Biochemistry, 2003. 42(32): p. 9804-9812.
61. Winkelmann, J., M. Leippe, and H. Bruhn, A novel saposin-like protein of Entamoeba histolytica with membrane-fusogenic activity. Molecular and biochemical parasitology, 2006. 147(1): p. 85-94.
62. Munford, R.S., P.O. Sheppard, and P.J. O'Hara, Saposin-like proteins (SAPLIP) carry out diverse functions on a common backbone structure. Journal of lipid research, 1995. 36(8): p. 1653-1663.
63. Laughlin, R.C. and L.A. Temesvari, Secreted and cell-surface adhesive proteins in Entamoeba histolytica. Molecular Medicine, 2005. 7(13).
64. Handal, G., Regulation of antioxidant enzymes in Entamoeba histolytica (Schaudinn, 1903). 2010, Staats- und Universitatsbibliothek Hamburg: Hamburg.
65. Choi, M.-H., et al., An unusual surface peroxiredoxin protects invasive Entamoeba histolytica from oxidant attack. Molecular and biochemical parasitology, 2005. 143(1): p. 80-89.
66. Muller, S., et al., Thiol-based redox metabolism of protozoan parasites. Trends in parasitology, 2003. 19(7): p. 320-328.
67. Al-Ardi, M.H., Illumination on the Structure and Characteristics of Entamoeba Histolytica Genome. 2021.
68. 69. Loftus, B., et al., The genome of the protistparasite Entamoeba histolytica. Nature, 2005. 433(7028): p. 865-868.
69. Clark, C.G., et al., New insights into the phylogeny ofEntamoeba species provided by analysis of four new small-subunit rRNA genes. International journal of systematic and evolutionary microbiology, 2006b. 56(9): p. 2235-2239.
70. Bhattacharya, S., I. Som, and A. Bhattacharya, The Ribosomal DNA Plasmids of Entamoeba. Parasitology Today, 1998. 14(5): p. 181-185.
71. Sanchez, L.B., et al., Fructose-1, 6-bisphosphate aldolases in amitochondriate protists constitute a single protein subfamily with eubacterial relationships. Gene, 2002. 295(1): p. 51-59.
72. Field, J., B. Rosenthal, and J. Samuelson, Early lateral transfer of genes encoding malic enzyme, acetyl-Co.A synthetase and alcohol dehydrogenases from anaerobic prokaryotes to Entamoebahistolytica. Molecular microbiology, 2000. 38(3): p. 446-455.
73. Bruchhaus, I. and E. Tannich, Purification and molecular characterization of the NAD (+)-dependent acetaldehyde/alcohol dehydrogenase from Entamoebahistolytica. Biochem. J, 1994. 303: p. 743-748.
74. 75. Rosenthal, B., et al., Evidence for the bacterial origin ofgenes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoebahistolytica. Journal of bacteriology, 1997. 179(11): p. 3736-3745.
75. McTavish, E.J., et al., How and why to build a unified tree of life. 2017. 39(11): p. 1700114.
76. 77. Wilson, I.W., et al., Genetic diversity and gene family expansions in members of the genus Entamoeba. 2019. 11(3): p. 688-705.
77. Choudhuri, S., Bioinformatics for beginners: genes, genomes, molecular evolution, databases and analytical tools. 2014: Elsevier.
78. Gibson, A.K.J.E., Genetic diversity and disease: The past, present, and future of an old idea. 2022. 76(S1): p. 20-36.
79. Hoban, S., et al., Global genetic diversity status and trends: towards a suite of Essential Biodiversity Variables (EBVs) for genetic composition. 2022.
80. Loftus, B., et al., The genome of the protist parasite Entamoebahistolytica. 2005. 433(7028): p. 865-868.
81. 82. Mahmood, S.A.F., H.M.J.C. Bakr, and M. Biology, Genetic variability of E. histolytica strains based on the polymorphism of the SREHP gene using nested PCR-RFLP in Erbil, North Iraq. 2020. 66(1): p. 82-87.
82. Labruyère, E., et al., Crosstalk between Entamoeba histolytica and the human intestinal tract during amoebiasis. 2019. 146(9): p. 1140-1149.
83. Teixeira, J.E., C.D.J.I. Huston, and immunity, Participation of the serine-rich Entamoeba histolytica protein in amebic phagocytosis of apoptotic host cells. 2008. 76(3): p. 959-966.
84. ElBakri, A., et al., Genetic variability of the Serine-Rich Entamoeba histolytica protein gene in clinical isolates from the United Arab Emirates. 2014. 31(2): p. 370-7.
85. Ayeh-Kumi, P.F., et al., Entamoebahistolytica: genetic diversity of clinical isolates from Bangladesh as demonstrated by polymorphisms in the serine-richgene. 2001. 99(2): p. 80-88.
86. Haghighi, A., et al., Geographic diversity among genotypes of Entamoeba histolytica field isolates. 2003. 41(8): p. 3748-3756.
87. Zhang, T. and S.L.J.V. Stanley Jr, DNA vaccination with the serine rich Entamoeba histolytica protein (SREHP) prevents amebic liver abscess in rodent models of disease. 1999. 18(9-10): p. 868-874.
88. Ali, V. and T. Nozaki, Current therapeutics, their problems, and sulfur-containing-amino-acid metabolism as a novel target against infections by "amitochondriate" protozoan parasites. Clinical microbiology reviews, 2007. 20(1): p. 164-187.
89. Fung, H.B. and T.-L. Doan, Tinidazole: a nitroimidazole antiprotozoal agent. Clinical therapeutics, 2005. 27(12): p. 1859-1884.
90. Stanley, S.L., Amoebiasis. The Lancet, 2003. 361(9362): p. 1025-1034.
91. Tazreiter, M.H., Reaction of the human parasite Entamoeba histolytica to metronidazole. 2010, uniwien. p. 12-16.
92. Akgun, Y., I.H. Tacyildiz, and Y. Celik, Amebic Liver Abscess: Changing Trends over 20Years. World journal of surgery, 1999. 23(1): p. 102-106.
93. Rossignol, J.-F.o., A. Ayoub, and M.S. Ayers, Treatment of diarrhea caused by giardia intestinalis and Entamoeba histolytica or E. Dispar: A randomized, double-blind, placebo-controlled study of nitazoxanide. Journal of Infectious Diseases, 2001. 184(3): p. 381-384.
94. Seifert, K., et al., Effects of Miltefosine and Other Alkylphosphocholines on Human Intestinal ParasiteEntamoeba histolytica. Antimicrobial agents and chemotherapy, 2001. 45(5): p. 1505-1510.
95. Croft, S.L., K. Seifert, and M. Duchone, Antiprotozoal activities of phospholipid analogues. Molecular and biochemical parasitology, 2003. 126(2): p. 165-172.
96. Walochnik, J., et al., Cytotoxic activities of alkylphosphocholines against clinical isolates of Acanthamoeba spp. Antimicrobial agents and chemotherapy, 2002. 46(3): p. 695-701.
97. Rang, H.P., et al., Pharmacology. 5th. London: Churchill Livingston, 2003: p. 648.
98. Upcroft, P. and J.A. Upcroft, Drug targets and mechanismsof resistance in the anaerobic protozoa. Clinical microbiology reviews, 2001. 14(1): p. 150-164.
99. Wassmann, C., et al., Metronidazole resistance in the protozoan parasite Entamoeba histolytica is associated with increased expression of iron-containingsuperoxide dismutase and peroxiredoxin and decreased expression of ferredoxin 1 and flavin reductase. Journal of Biological Chemistry, 1999. 274(37): p. 26051-26056.
100. Nzila, A. and L. Mwai, In vitro selection of Plasmodium falciparum drug-resistant parasite lines. Journal of antimicrobial chemotherapy, 2010. 65(3): p. 390-398.
101. Noedl, H., et al., Evidence of artemisinin-resistant malaria in western Cambodia. New England journal of medicine, 2008. 359(24): p. 2619-2620.
102. Noedl, H., D. Socheat, and W. Satimai, Artemisinin-resistant malaria in Asia. New England journal of medicine, 2009. 361(5): p. 540-541.
103. Muler, M., Mode of action of metronidazole on anaerobic bacteria and protozoa. Surgery, 1983. 93(1 Pt 2): p. 165-171.
104. Moreno, S.N. and R. Docampo, Mechanism of toxicity of nitro compounds used in the chemotherapy of trichomoniasis. Environmental health perspectives, 1985. 64: p. 199-208.
105. 106. West, S.B., et al., Drug residue formation from ronidazole, a 5-nitroimidazole. I. Characterization of in vitro protein alkylation. Chemico-biological interactions, 1982. 41(3): p. 265-279.
106. Ludlum, D.B., et al., Reaction of reduced metronidazole with guanosine to form an unstable adduct. Carcinogenesis, 1988. 9(4): p. 593-596.
107. Mason, R.P. and J.L. Holtzman, The role of catalytic superoxide formation in the O 2 inhibition of nitroreductase. Biochemical and biophysical research communications, 1975. 67(4): p. 1267-1274.
108. Bendesky, A., D. Menendez, and P. Ostrosky-Wegman, Is metronidazole carcinogenic? Mutation Research/Reviews in Mutation Research, 2002. 511(2): p. 133-144.
109. Muller, M., Reductive activation of nitroimidazoles in anaerobic microorganisms. Biochemical pharmacology, 1986. 35(1): p. 37-41.
110. 111. Chapman, A., et al., The generation of metronidazole radicals in hydrogenosomes isolated from Trichomonas vaginalis. Journal of general microbiology, 1985. 131(9): p. 2141-2144.
111. Rasoloson, D., et al., Mechanisms of in vitro development of resistance to metronidazole in Trichomonas vaginalis. Microbiology, 2002. 148(8): p. 2467-2477.
112. Leitsch, D., et al., Nitroimidazole action in Entamoeba histolytica: a central role for thioredoxin reductase. PLoS biology, 2007. 5(8): p. e211.
113. Leitsch, D., et al., Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Molecular microbiology, 2009. 72(2): p. 518-536.
114. Leitsch, D., D. Kolarich, and M. Duchene, The flavin inhibitor diphenyleneiodonium renders Trichomonas vaginalis resistant to metronidazole, inhibits thioredoxin reductase and flavin reductase, and shuts off hydrogenosomal enzymatic pathways. Molecular and biochemical parasitology, 2010. 171(1): p. 17-24.
73 Views | 89 Downloads
How to Cite
Alshaibani, H. A. A. “A Review of Entamoebahistolytica Genome, Virulence Factors, Phylogenetic Tree and Treatment”. World Journal of Current Medical and Pharmaceutical Research, Vol. 6, no. 1, Mar. 2024, pp. 26-35, doi:10.37022/wjcmpr.v6i1.316.
Review Articles