Host-Parasite interactions in Entamoeba histolytica and Entamoeba dispar: what have we learned from their genomes?

Abstract

Invasive amoebiasis caused by Entamoeba histolytica is a major global health problem. Virulence is a rare outcome of infection, occurring in fewer than 1 in 10 infections. Not all strains of the parasite are equally virulent, and understanding the mechanisms and causes of virulence is an important goal of Entamoeba research. The sequencing of the genome of E. histolytica and the related avirulent species Entamoeba dispar has allowed whole-genome-scale analyses of genetic divergence and differential gene expression to be undertaken. These studies have helped elucidate mechanisms of virulence and identified genes differentially expressed in virulent and avirulent parasites. Here, we review the current status of the E. histolytica and E. dispar genomes and the findings of a number of genome-scale studies comparing parasites of different virulence.

Figure 1

Key virulence factors of Entamoeba histolytica involved in pathogenic infections that have been identified by genome-scale investigations. 1 = Binding to epithelial extracellular matrix via Gal/GalNac lectin and EhSTIRP; and degradation of MUC2 polymers via secreted cysteine proteases. 2 = Subversion of host immune response, following binding of LPPG to host Toll-Like receptors 2 and 4, via degradation of reactive oxygen species by superoxide dismutase, NADPH:flavin oxidoreductase and peroxiredoxin. Fe-hydrogenase inhibits immune response by unknown mechanism. 3 = ‘Capping and Shedding’ of trophozoite surface antigens by host antibodies and lectins, involving cytoskeletal rearrangement to translocate antigen–antibody complexes to ‘uroid’ of cell for shedding. Putative function for EhROM1 in translocation. 4 = Direct contact between trophozoite and host or bacterial cell, leading to secretion of amoebapore-A, which forms pores in target cell membrane without need for receptor.

Figure 2

Comparison of colonisation of the colonic surface by Entamoeba histolytica and Entamoeba dispar. Panels show breakdown of mucus by E. histolytica after 0 h (a) and 2 h (b). Enlargement of region shows aggregates of trophozoites and recruited human cells (c). After 4 h, trophozoites begin to damage (d) and to penetrate epithelia (e). Conversely, after 4 h, E. dispar binds to, but does not degrade, the mucus barrier (f) and, as shown by manually removing the mucus layer, does not recruit immune cells to the epithelial surface (g). [Reprinted, with permission, from (44)].

Figure 3

Comparison of the current status of the Entamoeba histolytica and Entamoeba dispar genome annotations, indicating the relative proportions of genes with putative functions. ‘Annotated’ = Percentage of non-hypothetical genes in the annotation; ‘GO’ = Percentage of genes associated with a ‘Gene Ontology’ term, i.e. those with either a cellular component, molecular function or biological process; ‘EC’ = Percentage of genes with ‘Enzyme Commission’ numbers, i.e. enzymes identified as being involved in known chemical reactions. Based upon figures from AmoebaDB (–50). Based on most recent genome annotation (46).