Discrimination Experiments in Entamoeba and Evidence from Other Protists Suggest Pathogenic Amebas Cooperate with Kin to Colonize Hosts and Deter Rivals

Abstract

Entamoeba histolytica is one of the least understood protists in terms of taxa, clone, and kin discrimination/recognition ability. However, the capacity to tell apart same or self (clone/kin) from different or nonself (nonclone/nonkin) has long been demonstrated in pathogenic eukaryotes like Trypanosoma and Plasmodium, free-living social amebas (Dictyostelium, Polysphondylium), budding yeast (Saccharomyces), and in numerous bacteria and archaea (prokaryotes). Kin discrimination/recognition is explained under inclusive fitness theory; that is, the reproductive advantage that genetically closely related organisms (kin) can gain by cooperating preferably with one another (rather than with distantly related or unrelated individuals), minimizing antagonism and competition with kin, and excluding genetic strangers (or cheaters = noncooperators that benefit from others' investments in altruistic cooperation). In this review, we rely on the outcomes of in vitro pairwise discrimination/recognition encounters between seven Entamoeba lineages to discuss the biological significance of taxa, clone, and kin discrimination/recognition in a range of generalist and specialist species (close or distantly related phylogenetically). We then focus our discussion on the importance of these laboratory observations for E. histolytica's life cycle, host infestation, and implications of these features of the amebas' natural history for human health (including mitigation of amebiasis).

Anti-amebic effects of Chinese rhubarb (Rheum palmatum) leaves' extract, the anthraquinone rhein and related compounds

“…secrete into the milieu signals associated with cell proliferation, cell adhesion, cell movement, and stress-induced encystation (i.e. RasGap/ Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin [26,41,42]). Because encystation and abscess formation require cell aggregation (i.e.…”

“…Because encystation and abscess formation require cell aggregation (i.e. abscesses are bound to cell recruitment), we have postulated that disruption of E. histolytica capacity to group, via silencing of alleles yet to be discovered, or drugs that alter the chemistry of the recruitment signals secreted into the milieu, might be approaches to mitigating amebiasis [26]. Thus, by combining current or novel therapeutics (this paper) with the disruption of E. histolytica to aggregate, we might find new approaches to treatments [26,41,42].…”

“…A similar volume of DMSO was added to wells with ameba (i.e. "amebas in TYI-S-33 media þ DMSO") to control for potential solvent toxicity [22,23,24,25,26]. Metronidazole (market drug of choice to treat amebiasis) at 20 μM concentration was used as a positive control of inhibition.…”

“…The experiments were done in triplicate (total 24 wells; experimental design for "rhein extract" is depicted in Figure 1 top) during three independent experiments. Counts of viable ameba cells were estimated with a Cellometer Vision HS RF-150 (Nexcelom BioScience Lawrence, MA) as detailed previously [22,23,24,25,26]. Second, all ten isolated/synthetic anthraquinones were dissolved in DMSO (as in above), added to the suspensions of trophozoites at concentrations of 60 μM or 120 μM, and incubated for 24 h or 48 h at 37 C. Metronidazole, TYI-S-33 media or TYI-S-33 media þ DMSO were separately added to the trophozoites as in above (controls).…”

Trogocytosis in Unicellular Eukaryotes

“…Self-nonself discrimination is often used in the context of immune recognition and immunological tolerance. However, there is also a significant numbers of cases in which the term was used in a broader sense with the representative case being cannibalism between close species of the free-living eukaryotes [ 46 , 47 , 48 , 49 ]. Trogocytosis has been suggested to play a role in self-nonself discrimination in the social amoeba Dictyostelid species.…”