Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has limited effects on parasite gene expression

Ali, Ibne Karim M; Ehrenkaufer, Gretchen M; Hackney, Jason A; Singh, Upinder
January 2007
BMC Genomics;2007, Vol. 8, p1
Academic Journal
Background: In higher eukaryotes DNA methylation regulates important biological functions including silencing of gene expression and protection from adverse effects of retrotransposons. In the protozoan parasite Entamoeba histolytica, a DNA methyltransferase has been identified and treatment with 5-azacytidine (5-AzaC), a potent inhibitor of DNA methyltransferase, has been reported to attenuate parasite virulence. However, the overall extent of DNA methylation and its subsequent effects on global gene expression in this parasite are currently unknown. Results: In order to identify the genome-wide effects of DNA methylation in E. histolytica, we used a short oligonucleotide microarray representing 9,435 genes (~95% of all annotated amebic genes) and compared the expression profile of E. histolytica HM-1:IMSS parasites with those treated with 23 µM 5-AzaC for up to one week. Overall, 2.1% of genes tested were transcriptionally modulated under these conditions. 68 genes were upregulated and 131 genes down regulated (2-fold change; p-value < 0.05). Sodium-bisulfite treatment and sequencing of genes indicated that there were at least two subsets of genes with genomic DNA methylation in E. histolytica: (i) genes that were endogenously silenced by genomic DNA methylation and for which 5-AzaC treatment induced transcriptional derepression, and (ii) genes that have genomic DNA methylation, but which were not endogenously silenced by the methylation. We identified among the genes down regulated by 5-AzaC treatment a cysteine proteinase (2.m00545) and lysozyme (52.m00148) both of which have known roles in amebic pathogenesis. Decreased expression of these genes in the 5-AzaC treated E. histolytica may account in part for the parasites reduced cytolytic abilities. Conclusion: This work represents the first genome-wide analysis of DNA-methylation in Entamoeba histolytica and indicates that DNA methylation has relatively limited effects on gene expression in this parasite.


Related Articles

  • Identification of Genomic Responses to Collagen Binding by Trophozoites of Entamoeba histolytica. Debnath, Anjan; Das, Pradeep; Sajid, Mohammed; McKerrow, James H. // Journal of Infectious Diseases;8/1/2004, Vol. 190 Issue 3, p448 

    Attachment of Entamoeba histolytica trophozoites to collagen is a known stimulus for parasite activation, leading to subsequent tissue destruction and invasion. To identify cellular mechanisms of trophozoite activation, we assessed global variations in gene expression during collagen interaction...

  • The effect of an anti-inflammatory pentapeptide produced by Entamoeba histolytica on gene expression in the U-937 monocytic cell line. R. Silva-García; I. Estrada-García; R. Ramos-Payán; A. Torres-Salazar; M. Morales-Martínez; D. Arenas-Aranda; J. Giménez-Scherer; F. Blanco-Favela; M. Rico-Rosillo // Inflammation Research;Apr2008, Vol. 57 Issue 4, p145 

    Abstract. Objective:  Evaluate the Monocyte Locomotion Inhibitory Factor (MLIF) effect upon the expression of genes encoding human cytokines, receptors and related factors in the human cell line U-937. MLIF (Met-Gln-Cys-Asn-Ser) is an anti-inflammatory pentapeptide produced by...

  • Short hairpin RNA-mediated knockdown of protein expression in Entamoeba histolytica. Linford, Alicia S.; Moreno, Heriberto; Good, Katelyn R.; Hanbang Zhang; Singh, Upinder; Petri Jr., William A. // BMC Microbiology;2009, Vol. 9, Special section p1 

    Background: Entamoeba histolytica is an intestinal protozoan parasite of humans. The genome has been sequenced, but the study of individual gene products has been hampered by the lack of the ability to generate gene knockouts. We chose to test the use of RNA interference to knock down gene...

  • Differential distribution of a SINE element in the Entamoeba histolytica and Entamoeba dispar genomes: Role of the LINE-encoded endonuclease. Kumari, Vandana; Sharma, Rahul; Yadav, Vijay P.; Gupta, Abhishek K.; Bhattacharya, Alok; Bhattacharya, Sudha // BMC Genomics;2011, Vol. 12 Issue 1, p267 

    Background: Entamoeba histolytica and Entamoeba dispar are closely related protistan parasites but while E. histolytica can be invasive, E. dispar is completely non pathogenic. Transposable elements constitute a significant portion of the genome in these species; there being three families of...

  • Drug Resistance in Natural Isolates of Leishmania donovani s.l. Promastigotes Is Dependent of Pgp170 Expression. Messaritakis, Ippokratis; Christodoulou, Vasiliki; Mazeris, Apostolos; Koutala, Eleni; Vlahou, Antonia; Papadogiorgaki, Sevasti; Antoniou, Maria // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony...

  • Differential identification of Entamoeba spp. based on the analysis of 18S rRNA. Santos, Helena Lúcia Carneiro; Bandea, Rebecca; Martins, Luci Ana Fernandes; De Macedo, Heloisa Werneck; Peralta, Regina Helena Saramago; Peralta, Jose Mauro; Ndubuisi, Mackevin I.; Da Silva, Alexandre J. // Parasitology Research;Mar2010, Vol. 106 Issue 4, p883 

    Entamoeba histolytica is known to cause intestinal and extra-intestinal disease while the other Entamoeba species are not considered to be pathogenic. However, all Entamoeba spp. should be reported when identified in clinical samples. Entamoeba polecki, Entamoeba coli, and Entamoeba hartmanii...

  • The small GTPase EhRabB of Entamoeba histolytica is differentially expressed during phagocytosis. Hernandes-Alejandro, Mario; Calixto-Gálvez, Mercedes; López-Reyes, Israel; Salas-Casas, Andrés; Cázares-Ápatiga, Javier; Orozco, Esther; Rodríguez, Mario // Parasitology Research;Apr2013, Vol. 112 Issue 4, p1631 

    It has been described that the pathogenicity of Entamoeba histolytica is influenced by environmental conditions and that transcription profile changes occur during invasion, suggesting that gene expression may be involved in the virulence of this parasite. However, the molecular mechanisms that...

  • The Entamoeba histolytica genome: primary structure and expression of proteolytic enzymes. Tillack, Manuela; Biller, Laura; Irmer, Henriette; Freitas, Michelle; Gomes, Maria A; Tannich, Egbert; Bruchhaus, Iris // BMC Genomics;2007, Vol. 8, p1 

    Background: A number of studies have shown that peptidases and in particular cysteine peptidases constitute major pathogenicity factors in Entamoeba histolytica. Recent studies have suggested that a considerable number of genes coding for proteolytic enzymes are present within the E. histolytica...

  • New Assembly, Reannotation and Analysis of the Entamoeba histolytica Genome Reveal New Genomic Features and Protein Content Information. Lorenzi, Hernan A.; Puiu, Daniela; Miller, Jason R.; Brinkac, Lauren M.; Amedeo, Paolo; Hall, Neil; Caler, Elisabet V. // PLoS Neglected Tropical Diseases;Jun2010, Vol. 4 Issue 6, p1 

    Background: In order to maintain genome information accurately and relevantly, original genome annotations need to be updated and evaluated regularly. Manual reannotation of genomes is important as it can significantly reduce the propagation of errors and consequently diminishes the time spent...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics