Human amebiasis: breaking the paradigm?

Abstract

For over 30 years it has been established that the Entamoeba histolytica protozoan included two biologically and genetically different species, one with a pathogenic phenotype called E. histolytica and the other with a non-pathogenic phenotype called Entamoeba dispar. Both of these amoebae species can infect humans. E. histolytica has been considered as a potential pathogen that can cause serious damage to the large intestine (colitis, dysentery) and other extraintestinal organs, mainly the liver (amebic liver abscess), whereas E. dispar is a species that interacts with humans in a commensal relationship, causing no symptoms or any tissue damage. This paradigm, however, should be reconsidered or re-evaluated. In the present work, we report the detection and genotyping of E. dispar sequences of DNA obtained from patients with amebic liver abscesses, including the genotyping of an isolate obtained from a Brazilian patient with a clinical diagnosis of intestinal amebiasis that was previously characterized as an E. dispar species. The genetic diversity and phylogenetic analysis performed by our group has shown the existence of several different genotypes of E. dispar that can be associated to, or be potentiality responsible for intestinal or liver tissue damage, similar to that observed with E. histolytica.

Keywords: E. dispar; E. histolytica; genetic diversity; human amebiasis; phylogeny.

Figure 1.

Phylogenetic reconstruction through the neighbor-joining method from intergenic tRNA Dsp1-2 sequences of E. dispar and Hsp1-2 of E. histolytica. Bootstrap values with 2500 replications are indicated close to the node numbers. Bar (0.02) shows nucleotide substitutions at each position. Colors in the first column indicate the source of samples and strain: Red, DNA of ALA; Blue, strains from fecal samples; Green, strains obtained in non-dysenteric amebic colitis; Yellow, animal source. The second column indicates the geographical region of the samples: Red, America; Blue, Asia; Green, Europe; White, data not available.

Figure 2.

Four phylogenetic reconstructions of intergenic tRNA sequences of E. dispar, E. histolytica and ICB-ADO strains (A, SQD3-5; B, Dsp5-6; C, StgaD3-5; and D, NKD3-5) performed through the neighbor-joining method. Bootstraps values with 2500 replications are indicated close to the node numbers. The ICB-ADO strain is included in the E. dispar group in all phylogenies.

Figure 3.

Four different hypotheses may explain the presence of E. dispar in liver abscesses. First, E. histolytica (blue) species invade the intestinal mucosa, producing erosion and ulceration of intestinal tissue. Both species are then placed in portal circulation and seeded into the liver. E. dispar (red) does not produce tissue damage but may take advantage of the pathogenic capacity of the E. histolytica species (1). The second possible explanation proposes that the two species are similarly responsible of both the intestinal and liver damage (2). The third hypothesis deals with bacteria-mediated pathogenicity. This suggests that the pathogenesis of at least some E. dispar strains may be mediated by (Black points) a type of bacterial flora in a particular host (3). The fourth hypothesis (Table 2) suggest that recombination events between E. histolytica and E. dispar species. In the right column are included the samples that could represent the possible hypothetical scenarios.