Apoptosis-inducing factor-like protein-mediated stress and metronidazole-responsive programmed cell death pathway in Entamoeba histolytica

Apoptosis-inducing factor (AIF) is the major component of the caspase-independent cell death pathway that is considered to be evolutionarily ancient. Apoptosis is generally evolved with multicellularity as a prerequisite for the elimination of aged, stressed, or infected cells promoting the survival of the organism. Our study reports the presence of a putative AIF-like protein in Entamoeba histolytica, a caspase-deficient primitive protozoan, strengthening the concept of occurrence of apoptosis in unicellular organisms as well. The putative cytoplasmic EhAIF migrates to the nucleus on receiving stresses that precede its binding with DNA, following chromatin degradation and chromatin condensation as evident from both in vitro and in vivo experiments. Down-regulating the EhAIF expression attenuates the apoptotic features of insulted cells and increases the survival potency in terms of cell viability and vitality of the trophozoites, whereas over-expression of the EhAIF effectively enhances the phenomena. Interestingly, metronidazole, the most widely used drug for amoebiasis treatment, is also potent to elicit similar AIF-mediated cell death responses like other stresses indicating the AIF-mediated cell death could be the probable mechanism of trophozoite-death by metronidazole treatment. The occurrence of apoptosis in a unicellular organism is an interesting phenomenon that might signify the altruistic death that overall improves the population health.

Automated summary

Our study shows the presence of a AIF-like protein in a caspase-deficient protozoan, suggesting the occurrence of apoptosis in unicellular organisms. The protein migrates to the nucleus upon stress and is involved in chromatin degradation and condensation. Down-regulating its expression attenuates apoptotic features, while over-expression enhances them. The widely-used drug metronidazole induces similar AIF-mediated cell death, indicating it as a probable mechanism of amoebicidal action. The occurrence of apoptosis in unicellular organisms may signify altruistic death that benefits the population health.