Current Tropical Medicine Reports

, Volume 3, Issue 4, pp 158–163 | Cite as

The E. histolytica Genome Structure and Virulence

  • Carol A. Gilchrist
Entamoeba Histolytica (Z Noor, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Entamoeba Histolytica


The outcome of an Entamoeba histolytica infection is variable, and the contribution of genetic diversity within E. histolytica to human disease is not fully understood. The information provided by the whole genome sequence of the E. histolytica reference laboratory strain (HM-1:IMSS), and 13 additional laboratory strains have been made publically available. In this review, theories on the source of the unexpected level of structural diversity found in E. histolytica will be discussed.


Single nucleotide polymorphisms Genome Cyclin-2 Structural diversity 



This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) grants AI103536-01 and AI043596. The funders had no role in study design, data collection and analysis, or decision to submit for publication

Compliance with Ethical Standards

Conflict of Interest

Carol A. Gilchrist declares grant funding from the Bill and Melinda Gates Foundation and from the NIAID.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet [Internet]. 2010 [cited 2011 Jul 18];375:1969–87. Available from:
  2. 2.
    Fischer Walker CL, Aryee MJ, Boschi-Pinto C, Black RE. Estimating diarrhea mortality among young children in low and middle income countries. PLoS One [Internet]. 2012 [cited 2012 Jan 27];7:e29151. Available from:
  3. 3.•
    Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case–control study. Lancet [Internet]. 2013 [cited 2013 Aug 9];382:209–22. Available from: The GEMS study is one of the largest studies in low and middle income countires of childhood enteric infections.
  4. 4.
    Haque R, Huston CD, Hughes M, Houpt E, Petri WAJ. Amebiasis. N. Engl. J. Med. [Internet]. 2003 [cited 2012 Jan 27];348:1565–73. Available from:
  5. 5.
    Duggal P, Haque R, Roy S, Mondal D, Sack RB, Farr BM, et al. Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica. J. Infect. Dis. [Internet]. 2004 [cited 2012 Jan 29];189:520–6. Available from:
  6. 6.
    Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, et al. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. J. Clin. Invest. [Internet]. 2011 [cited 2012 Mar 27];121:1191–8. Available from:
  7. 7.•
    Gilchrist CA, Petri SE, Schneider BN, Reichman DJ, Jiang N, Begum S, et al. Role of the gut microbiota of children in diarrhea due to the protozoan parasite Entamoeba histolytica. J. Infect. Dis. [Internet]. 2016 [cited 2016 Jan 12];213:1579–85. Available from: In this publication the authors report that both high E. histolytica parasite burdens and expansion of the pathobiont Prevotella copri was associated with diarrhea. Suggesting that the amount of parasite and the composition of the microbiota affect the disease severity.
  8. 8.•
    Burgess SL, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, et al. Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis. MBio [Internet]. 2014 [cited 2015 Jan 21];5:e01817. Available from: Colonization with the mouse gut with the Clostridia bacteria, Segmented Filamentous Bacteria (SFB), resulted in changes in the innate immune system and protection from E. histolytica infection.
  9. 9.
    Korpe PS, Liu Y, Siddique A, Kabir M, Ralston K, Ma JZ, et al. Breast milk parasite-specific antibodies and protection from amebiasis and cryptosporidiosis in Bangladeshi infants: a prospective cohort study. Clin. Infect. Dis. [Internet]. 2013 [cited 2013 May 2];56:988–92. Available from:
  10. 10.••
    Gilchrist CA, Ali IKM, Kabir M, Alam F, Scherbakova S, Ferlanti E, et al. A multilocus sequence typing system ( MLST ) reveals a high level of diversity and a genetic component to Entamoeba histolytica virulence. BMC Microbiol. [Internet]. 2012 [cited 2012 Aug 30];12:151. Available from: The work described in this paper used polymorphic SNPs to describe the diversity of E. histolytica genotypes and their link to virulence.
  11. 11.••
    Ali IKM, Haque R, Alam F, Kabir M, Siddique A, Petri WAJ. Evidence for a link between locus R-R sequence type and outcome of infection with Entamoeba histolytica. Clin. Microbiol. Infect. [Internet]. 2012 [cited 2012 May 1];18:E235-7. Available from: The work derscribed in this paper used tRNA gene-linked short tandem repeats to describe the diversity of E. histolytica genotypes and their link to virulence.
  12. 12.
    Ali IKM, Mondal U, Roy S, Haque R, Petri WAJ, Clark CG. Evidence for a link between parasite genotype and outcome of infection with Entamoeba histolytica . J. Clin. Microbiol. [Internet]. 2007 [cited 2012 Jan 29];45:285–9. Available from:
  13. 13.
    Jaiswal V, Ghoshal U, Mittal B, Dhole TN, Ghoshal UC. Association between allelic variation due to short tandem repeats in tRNA gene of Entamoeba histolytica and clinical phenotypes of amoebiasis. Acta Trop. [Internet]. 2014 [cited 2016 Jun 6];133:1–7. Available from:
  14. 14.••
    Das K, Mukherjee AK, Chowdhury P, Sehgal R, Bhattacharya MK, Hashimoto T, et al. Multilocus sequence typing system (MLST) reveals a significant association of Entamoeba histolytica genetic patterns with disease outcome. Parasitol. Int. [Internet]. 2014 [cited 2015 Apr 8];63:308–14. Available from: In this paper a new multilocus genotyping system which used information from both the tRNA linked short tandem repeats (STR) and the polymorphic Chitinase gene to characterize E. histolyitca DNA isolated from Indian asymptomatic, diarheal and amebic liver abscess. Diarrheal isolates were genetic distinct from those causing liver abscess or asymptomatically colonizing the host.
  15. 15.••
    Nozaki T, Bhattacharya A, editors. Amebiasis: Biology and Pathogenesis of Entamoeba. Springer, 2014. This book provides a comprehensive review of both the biology and pathogenesis of Entamoeba histolytica.Google Scholar
  16. 16.
    Clark CG, Alsmark UCM, Tazreiter M, Saito-Nakano Y, Ali V, Marion S, et al. Structure and content of the Entamoeba histolytica genome. Adv. Parasitol. [Internet]. 2007 [cited 2011 Aug 6];65:51–190. Available from:
  17. 17.
    Loftus B, Anderson I, Davies R, Alsmark UCM, Samuelson J, Amedeo P, et al. The genome of the protist parasite Entamoeba histolytica. Nature [Internet]. 2005 [cited 2011 Oct 10];433:865–8. Available from:
  18. 18.
    Weedall GD, Hall N. Evolutionary genomics of Entamoeba. Res. Microbiol. [Internet]. 2011 [cited 2012 Nov 10];162:637–45. Available from:
  19. 19.
    Lorenzi HA, Puiu D, Miller JR, Brinkac LM, Amedeo P, Hall N, et al. New assembly, reannotation and analysis of the Entamoeba histolytica genome reveal new genomic features and protein content information. PLoS Negl. Trop. Dis. [Internet]. 2010 [cited 2012 Feb 6];4:e716. Available from:
  20. 20.•
    Weedall GD, Clark CG, Koldkjaer P, Kay S, Bruchhaus I, Tannich E, et al. Genomic diversity of the human intestinal parasite Entamoeba histolytica. Genome Biol. [Internet]. 2012 [cited 2012 Oct 5];13:R38. Available from: This paper describes the resequencing 10 of the E. histolytica strains in laboratory culture.
  21. 21.•
    Zermeño V, Ximénez C, Morán P, Valadez A, Valenzuela O, Rascón E, et al. Worldwide genealogy of Entamoeba histolytica: an overview to understand haplotype distribution and infection outcome. Infect. Genet. Evol. [Internet]. 2013 [cited 2016 Jun 6];17:243–52. Available from: This paper describes the world wide diversity of the E. histolytica tRNA gene-linked short tandem repeats.
  22. 22.
    Haghighi A, Kobayashi S, Takeuchi T, Thammapalerd N, Nozaki T. Geographic diversity among genotypes of Entamoeba histolytica field isolates. J. Clin. Microbiol. [Internet]. 2003 [cited 2012 Jan 30];41:3748–56. Available from:
  23. 23.
    Haghighi A, Kobayashi S, Takeuchi T, Masuda G, Nozaki T. Remarkable genetic polymorphism among Entamoeba histolytica isolates from a limited geographic area. J. Clin. Microbiol. [Internet]. 2002 [cited 2012 Jan 30];40:4081–90. Available from:
  24. 24.
    Escueta-de Cadiz A, Kobayashi S, Takeuchi T, Tachibana H, Nozaki T. Identification of an avirulent Entamoeba histolytica strain with unique tRNA-linked short tandem repeat markers. Parasitol. Int. [Internet]. 2010 [cited 2012 Jan 30];59:75–81. Available from:
  25. 25.
    Parfrey LW, Lahr DJG, Katz LA. The dynamic nature of eukaryotic genomes. Mol. Biol. Evol. [Internet]. 2008 [cited 2016 Jun 6];25:787–94. Available from:
  26. 26.
    Lohia A, Mukherjee C, Majumder S, Dastidar PG. Genome re-duplication and irregular segregation occur during the cell cycle of Entamoeba histolytica. Biosci. Rep. [Internet]. 2007 [cited 2012 May 1];27:373–84. Available from:
  27. 27.
    Mukherjee C, Clark CG, Lohia A. Entamoeba shows reversible variation in ploidy under different growth conditions and between life cycle phases. PLoS Negl. Trop. Dis. [Internet]. 2008 [cited 2012 May 1];2:e281. Available from:
  28. 28.
    Lorenzi H, Thiagarajan M, Haas B, Wortman J, Hall N, Caler E. Genome wide survey, discovery and evolution of repetitive elements in three Entamoeba species. BMC Genomics [Internet]. 2008 [cited 2012 May 1];9:595. Available from:
  29. 29.
    Das K, Ganguly S. Evolutionary genomics and population structure of Entamoeba histolytica. Comput. Struct. Biotechnol. J. [Internet]. 2014 [cited 2016 May 20];12:26–33. Available from:
  30. 30.
    Weedall GD, Sherrington J, Paterson S, Hall N. Evidence of gene conversion in genes encoding the Gal/GalNac lectin complex of Entamoeba. PLoS Negl. Trop. Dis. [Internet]. 2011 [cited 2015 Nov 24];5:e1209. Available from:
  31. 31.
    Ghosh S, Frisardi M, Ramirez-Avila L, Descoteaux S, Sturm-Ramirez K, Newton-Sanchez OA, et al. Molecular epidemiology of Entamoeba spp.: evidence of a bottleneck (demographic sweep) and transcontinental spread of diploid parasites. J. Clin. Microbiol. [Internet]. American Society for Microbiology; 2000 [cited 2012 Feb 1];38:3815–21. Available from:
  32. 32.
    Loman NJ, Misra R V, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, et al. Performance comparison of benchtop high-throughput sequencing platforms. Nat. Biotechnol. [Internet]. 2012 [cited 2013 Feb 10];30:434–9. Available from:
  33. 33.
    Laver T, Harrison J, O’Neill PA, Moore K, Farbos A, Paszkiewicz K, et al. Assessing the performance of the Oxford Nanopore Technologies MinION. Biomol. Detect. Quantif. [Internet]. 2015 [cited 2016 Jun 15];3:1–8. Available from:
  34. 34.
    Loman NJ, Quick J, Simpson JT. A complete bacterial genome assembled de novo using only nanopore sequencing data. Nat. Methods [Internet]. 2015 [cited 2016 Jun 15];12:733–5. Available from:
  35. 35.
    Lou DI, Hussmann JA, McBee RM, Acevedo A, Andino R, Press WH, et al. High-throughput DNA sequencing errors are reduced by orders of magnitude using circle sequencing. Proc. Natl. Acad. Sci. [Internet]. 2013 [cited 2013 Nov 16]; Available from:
  36. 36.
    Altmann A, Weber P, Bader D, Preuss M, Binder EB, Müller-Myhsok B. A beginners guide to SNP calling from high-throughput DNA-sequencing data. Hum. Genet. [Internet]. 2012 [cited 2016 Jun 15];131:1541–54. Available from:
  37. 37.
    Bhattacharya D, Haque R, Singh U. Coding and noncoding genomic regions of Entamoeba histolytica have significantly different rates of sequence polymorphisms: implications for epidemiological studies. J. Clin. Microbiol. [Internet]. 2005 [cited 2012 Jan 30];43:4815–9. Available from:
  38. 38.
    Altschul SF, Boguski MS, Gish W, Wootton JC. Issues in searching molecular sequence databases. Nat. Genet. [Internet]. 1994 [cited 2016 Jun 15];6:119–29. Available from:
  39. 39.
    Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A. 1998;95:3140–5.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Aurrecoechea C, Barreto A, Brestelli J, Brunk BP, Caler E V, Fischer S, et al. AmoebaDB and MicrosporidiaDB: functional genomic resources for Amoebozoa and Microsporidia species. Nucleic Acids Res. [Internet]. 2011 [cited 2012 Jan 30];39:D612-9. Available from:
  41. 41.
    Branscomb E, Predki P. On the high value of low standards. J. Bacteriol. [Internet]. 2002 [cited 2016 Jun 8];184:6406–9; discussion 6409. Available from:
  42. 42.
    Ali IKM, Hossain MB, Roy S, Ayeh-Kumi PF, Petri, William A J, Haque R, et al. Entamoeba moshkovskii infections in children, Bangladesh. Emerg. Infect. Dis. 2003;9:580–4.Google Scholar
  43. 43.
    Shimokawa C, Kabir M, Taniuchi M, Mondal D, Kobayashi S, Ali IKM, et al. Entamoeba moshkovskii is associated with diarrhea in infants and causes diarrhea and colitis in mice. J. Infect. Dis. [Internet]. 2012 [cited 2014 Jul 14];206:744–51. Available from:
  44. 44.
    Royer TL, Gilchrist C, Kabir M, Arju T, Ralston KS, Haque R, et al. Entamoeba bangladeshi nov. sp., Bangladesh. Emerg. Infect. Dis. [Internet]. 2012 [cited 2012 Nov 7];18:1543–5. Available from:
  45. 45.
    Diamond LS, Clark CG. A redescription of Entamoeba histolytica Schaudinn, 1903 (Emended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1925. J. Eukaryot. Microbiol. [Internet]. [cited 2012 May 1];40:340–4. Available from:
  46. 46.
    Haque R, Faruque AS, Hahn P, Lyerly DM, Petri WAJ. Entamoeba histolytica and Entamoeba dispar infection in children in Bangladesh. J. Infect. Dis. 175:734–6.Google Scholar
  47. 47.
    Wilson IW, Weedall GD, Hall N. Host-parasite interactions in Entamoeba histolytica and Entamoeba dispar: what have we learned from their genomes? Parasite Immunol. [Internet]. 2012 [cited 2012 May 1];34:90–9. Available from:
  48. 48.
    Willhoeft U, Buss H, Tannich E. DNA sequences corresponding to the ariel gene family of Entamoeba histolytica are not present in E. dispar. Parasitol. Res. [Internet]. 1999 [cited 2016 Jun 13];85:787–9. Available from:
  49. 49.
    Willhoeft U, Hamann L, Tannich E. A DNA sequence corresponding to the gene encoding cysteine proteinase 5 in Entamoeba histolytica is present and positionally conserved but highly degenerated in Entamoeba dispar. Infect. Immun. [Internet]. 1999 [cited 2016 Jun 13];67:5925–9. Available from:
  50. 50.
    Tachibana H, Yanagi T, Pandey K, Cheng X-J, Kobayashi S, Sherchand JB, et al. An Entamoeba sp. strain isolated from rhesus monkey is virulent but genetically different from Entamoeba histolytica. Mol. Biochem. Parasitol. [Internet]. 2007 [cited 2016 Sep 15];153:107–14. Available from:
  51. 51.
    Ehrenkaufer GM, Weedall GD, Williams D, Lorenzi HA, Caler E, Hall N, et al. The genome and transcriptome of the enteric parasite Entamoeba invadens, a model for encystation. Genome Biol. [Internet]. 2013 [cited 2016 Sep 15];14:R77. Available from:
  52. 52.
    Tawari B, Ali IKM, Scott C, Quail MA, Berriman M, Hall N, et al. Patterns of evolution in the unique tRNA gene arrays of the genus Entamoeba. Mol. Biol. Evol. [Internet]. 2008 [cited 2016 Sep 15];25:187–98. Available from:
  53. 53.
    Haque R, Ali IK, Akther S, Petri WA. Comparison of PCR, isoenzyme analysis, and antigen detection for diagnosis of Entamoeba histolytica infection. J. Clin. Microbiol. [Internet]. 1998 [cited 2015 May 8];36:449–52. Available from:
  54. 54.
    Regan CS, Yon L, Hossain M, Elsheikha HM. Prevalence of Entamoeba species in captive primates in zoological gardens in the UK. PeerJ [Internet]. 2014 [cited 2016 Jun 14];2:e492. Available from:
  55. 55.
    Ngui R, Angal L, Fakhrurrazi SA, Lian YLA, Ling LY, Ibrahim J, et al. Differentiating Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii using nested polymerase chain reaction (PCR) in rural communities in Malaysia. Parasit. Vectors [Internet]. 2012 [cited 2016 Jun 14];5:187. Available from:
  56. 56.
    Lau YL, Anthony C, Fakhrurrazi SA, Ibrahim J, Ithoi I, Mahmud R. Real-time PCR assay in differentiating Entamoeba histolytica, Entamoeba dispar, and Entamoeba moshkovskii infections in Orang Asli settlements in Malaysia. Parasit. Vectors [Internet]. 2013 [cited 2014 Oct 13];6:250. Available from:
  57. 57.
    Nixon JEJ, Wang A, Field J, Morrison HG, McArthur AG, Sogin ML, et al. Evidence for lateral transfer of genes encoding ferredoxins, nitroreductases, NADH oxidase, and alcohol dehydrogenase 3 from anaerobic prokaryotes to Giardia lamblia and Entamoeba histolytica. Eukaryot. Cell [Internet]. 2002 [cited 2012 Sep 11];1:181–90. Available from:
  58. 58.
    Rosenthal B, Mai Z, Caplivski D, Ghosh S, de la Vega H, Graf T, et al. Evidence for the bacterial origin of genes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoeba histolytica. J. Bacteriol. [Internet]. 1997 [cited 2016 Jun 13];179:3736–45. Available from:
  59. 59.
    Alsmark UC, Sicheritz-Ponten T, Foster PG, Hirt RP, Embley TM. Horizontal gene transfer in eukaryotic parasites: a case study of Entamoeba histolytica and Trichomonas vaginalis. Methods Mol. Biol. [Internet]. 2009 [cited 2016 Jun 13];532:489–500. Available from:
  60. 60.
    Quick J, Loman NJ, Duraffour S, Simpson JT, Severi E, Cowley L, et al. Real-time, portable genome sequencing for Ebola surveillance. Nature [Internet]. 2016 [cited 2016 Jun 15];530:228–32. Available from:

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of Medicine/Division of Infectious Diseases, School of MedicineUniversity of VirginiaCharlottesvilleUSA

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