Uniqueness of Entamoeba sulfur metabolism: sulfolipid metabolism that plays pleiotropic roles in the parasitic life cycle

Abstract

Sulfur metabolism is ubiquitous and terminally synthesizes various biomolecules that are crucial for organisms, such as sulfur-containing amino acids and co-factors, sulfolipids and sulfated saccharides. Entamoeba histolytica, a protozoan parasite responsible for amoebiasis, possesses the unique sulfur metabolism features of atypical localization and its terminal product being limited to sulfolipids. Here, we present an overall scheme of E. histolytica sulfur metabolism by relating all sulfotransferases and sulfatases to their substrates and products. Furthermore, a novel sulfur metabolite, fatty alcohol disulfates, was identified and shown to play an important role in trophozoite proliferation. Cholesteryl sulfate, another synthesized sulfolipid, was previously demonstrated to play an important role in encystation, a differentiation process from proliferative trophozoite to dormant cyst. Entamoeba survives by alternating between these two distinct forms; therefore, Entamoeba sulfur metabolism contributes to the parasitic life cycle via its terminal products. Interestingly, this unique feature of sulfur metabolism is not conserved in the nonparasitic close relative of Entamoeba, Mastigamoeba, because lateral gene transfer-mediated acquisition of sulfatases and sulfotransferases, critical enzymes conferring this feature, has only occurred in the Entamoeba lineage. Hence, our findings suggest that sulfolipid metabolism has a causal relationship with parasitism.

Non-vesicular Lipid Transport Machinery in Entamoeba histolytica

“…EhLPPG induces in vitro formation of human neutrophil extracellular traps (NETs) (Ávila et al, 2016 ). Sulfolipids are one of the terminally synthesized bio-molecules of sulfur metabolism, shown to play an important role in trophozoites proliferation and differentiation processes (Mi-Ichi et al, 2017 ). For instance, fatty alcohol disulfates plays a crucial role in trophozoites proliferation (Mi-Ichi et al, 2017 ).…”

“…Sulfolipids are one of the terminally synthesized bio-molecules of sulfur metabolism, shown to play an important role in trophozoites proliferation and differentiation processes (Mi-Ichi et al, 2017 ). For instance, fatty alcohol disulfates plays a crucial role in trophozoites proliferation (Mi-Ichi et al, 2017 ). Cholesteryl sulfate, another sulfolipid plays a central role in encystation, a differentiation process from the motile trophozoites to the dormant cysts (Mi-Ichi et al, 2017 ).…”

“…For instance, fatty alcohol disulfates plays a crucial role in trophozoites proliferation (Mi-Ichi et al, 2017 ). Cholesteryl sulfate, another sulfolipid plays a central role in encystation, a differentiation process from the motile trophozoites to the dormant cysts (Mi-Ichi et al, 2017 ). Furthermore, sulfur metabolism, in which sulfolipids are generated, is not conserved in other free-living amoebae, indicating a causal relationship of sulfur metabolism with parasitism (Mi-Ichi et al, 2017 ).…”

“…Cholesteryl sulfate, another sulfolipid plays a central role in encystation, a differentiation process from the motile trophozoites to the dormant cysts (Mi-Ichi et al, 2017 ). Furthermore, sulfur metabolism, in which sulfolipids are generated, is not conserved in other free-living amoebae, indicating a causal relationship of sulfur metabolism with parasitism (Mi-Ichi et al, 2017 ). Lysophosphatidylinositol was shown to stimulate natural killer T (NKT) cells and to induce selective production of IFN-γ but not IL-4 in a CD1-d restricted manner in murine systems (Aiba et al, 2016 ).…”

Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences

“…ATP imported from the cytosol is used for the activation of sulfate by the action of three enzymes, ATP sulfurylase (AS), adenosine-5 -phosphosulfokinase (APSK), and inorganic pyrophosphatase [17]. This process yields activated sulfates such as 3 -phosphoadenosine-5 -phosphosulfate (PAPS) [17] utilized for the synthesis of sulfur-containing lipids in the cytosol [18].…”