Lipids in Entamoeba histolytica: Host-Dependence and Virulence Factors

Abstract

Lipids are essential players in parasites pathogenesis. In particular, the highly phagocytic trophozoites of Entamoeba histolytica, the causative agent of amoebiasis, exhibit a dynamic membrane fusion and fission, in which lipids strongly participate; particularly during the overstated motility of the parasite to reach and attack the epithelia and ingest target cells. Synthesis and metabolism of lipids in this protozoan present remarkable difference with those performed by other eukaryotes. Here, we reviewed the current knowledge on lipids in E. histolytica. Trophozoites synthesize phosphatidylcholine and phosphatidylethanolamine by the Kennedy pathway; and sphingolipids, phosphatidylserine, and phosphatidylinositol, by processes similar to those used by other eukaryotes. However, trophozoites lack enzymes for cholesterol and fatty acids synthesis, which are scavenged from the host or culture medium by specific mechanisms. Cholesterol, a fundamental molecule for the expression of virulence, is transported from the medium into the trophozoites by EhNPC1 and EhNPC2 proteins. Inside cells, lipids are distributed by different pathways, including by the participation of the endosomal sorting complex required for transport (ESCRT), involved in vesicle fusion and fission. Cholesterol interacts with the phospholipid lysobisphosphatidic acid (LBPA) and EhADH, an ALIX family protein, also involved in phagocytosis. In this review, we summarize the known information on phospholipids synthesis and cholesterol transport as well as their metabolic pathways in E. histolytica; highlighting the mechanisms used by trophozoites to dispose lipids involved in the virulence processes.

Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis

“…The parasite genome so far has not shown the presence of any gene related to sterol synthesis. This further supports the notion that the parasite takes cholesterol from its external milieu and transports it via vesicular network ( Bolaños et al., 2016 ; Castellanos-Castro et al., 2020 ). Bolanos et al.…”

“…Also cholesterol:phospholipid ratio of amebic cells is 0.8 as compared to mammalian cells, which is 0.3 in whole cells ( Aley et al, 1980 ; Vance, 2015 ). Considering the peculiar lipid composition of the parasite and a repertoire of 27 putative unexplored enzymes involved in lipid metabolic pathway ( Castellanos-Castro et al., 2020 ), the parasite offers a promising avenue for anti-amebic drug targets.…”

“…Further, SL metabolism is also known to be linked with PC and PE metabolism ( Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania, 2017 ; Zufferey and Mamoun, 2002 ; Peacock et al., 2007 ). However, sphingomyelin (SM) is present at very low levels in the trophozoites under normal conditions ( Aley et al, 1980 ; Cerbón and Flores, 1981 ) but it cannot be ruled out that the parasite fulfills its PE requirement through SL metabolism and Kennedy pathway ( Gulati et al, 2015 ) as its genome codes for a putative sphingomyelin phosphodiesterase (EHI_007460) and another similar enzyme (EHI_040600) ( Njoya et al., 2014 ; Castellanos-Castro et al., 2020 ). These enzymes carry out the conversion of SM to phosphocholine which is then directed to the Kennedy pathway.…”

The Mastigamoeba balamuthi Genome and the Nature of the Free-Living Ancestor of Entamoeba

“…The FA biosynthesis pathway is predicted to have been lost prior to the emergence of the LCAA, as both E. histolytica and M. balamuthi do not encode enzymes dedicated to de novo FA synthesis, including multifunctional FA synthase (type I FAS), which are all present in D. discoideum . However, similarly to E. histolytica ( Castellanos-Castro et al. 2020 ), Mastigamoeba encodes enzymes of FA elongation ( supplementary fig.…”

Signals and signal transduction pathways in Entamoeba histolytica during the life cycle and when interacting with bacteria or human cells

“…In E. invadens , PKC inhibitors are able to block growth and cyst development (Makioka et al, 2000) and PLD activity increases at early stages of encystation (Ehrenkaufer et al, 2013). Most enzymes involved in lipid signaling have homologs in E. histolytica (Castellanos‐Castro et al, 2020). Finally, an atypical mitogen‐activated protein kinase known as MAPK15 has been associated with encystation.…”