Identification and partial characterization of a lipophosphoglycan from a pathogenic strain of Entamoeba histolytica

Bhattacharya, Alok; Prasad, R.; Sacks, David L.

doi:10.1016/0166-6851(92)90163-e

Cited by 40 publications

(24 citation statements)

References 19 publications

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“…The enzymes of GPI anchor biosynthesis are thought to be excellent targets for chemotherapy in many parasite infections, and GPI anchors have also been targets of immunoprophylaxis (6,26,34,47). Nothing is known about the GPI anchor biosynthetic pathway of E. histolytica and the enzymes that are involved.…”

mentioning

confidence: 99%

Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells

et al. 2005

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Glycosylphosphatidylinositol (GPI)-anchored molecules such as cell surface Gal/GalNAc lectin and proteophosphoglycans of the protozoan parasite Entamoeba histolytica are thought to be involved in pathogenesis. Here, we report the identification of genes that may be involved in the GPI biosynthetic pathway of E. histolytica by use of bioinformatic tools applied to the recently published genome sequence. Of the genes identified, one of the early genes, GlcNAc-phosphatidylinositol deacetylase (PIG-L), was partially characterized. Cell lines deficient in E. histolytica PIG-L (EhPL-AS) or overproducing it (EhPL-S) were generated by expressing the gene in the antisense or sense orientation, respectively, in a tetracycline-inducible system. The overexpressing cells showed higher EhPIG-L activity and increased production of GlcN-PI. Conversely, cells expressing the antisense RNA displayed reduced GlcN-PI production. The total number of GPI-containing molecules was also reduced in these cells, as demonstrated by Alexa 488 fluorescently labeled proaerolysin labeling. The distribution of GPI-linked PPG and Gal/GalNAc lectin was altered in the tetracycline-induced EhPL-AS cell lines. Further, the antisense-blocked cells showed 36% suppression of cell growth, 50 to 60% inhibition of fluid phase endocytosis, and about 50% inhibition of adhesion to target cells. Therefore, our data suggest the importance of GPI anchors in regulating some of the events in amoebic pathogenesis. They also demonstrated the use of antisense RNA-mediated inhibition of GPI biosynthetic enzymes as an approach to decrease the amount of GPI conjugates in E. histolytica.

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Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells

et al. 2005

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“…These molecules have been implicated in host-parasite interactions based on the finding that nonvirulent and virulent strains of Entamoeba histolytica express different amounts and structures of EhLPPG [39–42]. Recent research has shown that EhLPPG are the primary NKT cell ligands, helping to explain why CD1d−/− mice show significantly larger liver abscesses [43, 44].…”

Section: Adherencementioning

confidence: 99%

A Sequential Model of Host Cell Killing and Phagocytosis byEntamoeba histolytica

Sateriale

Huston

2011

Journal of Parasitology Research

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The protozoan parasite Entamoeba histolytica is responsible for invasive intestinal and extraintestinal amebiasis. The virulence of Entamoeba histolytica is strongly correlated with the parasite's capacity to effectively kill and phagocytose host cells. The process by which host cells are killed and phagocytosed follows a sequential model of adherence, cell killing, initiation of phagocytosis, and engulfment. This paper presents recent advances in the cytolytic and phagocytic processes of Entamoeba histolytica in context of the sequential model.

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“…These SCID mice demonstrated a high degree of protection against amebic liver abscess development. [25] However, production of amebic LPGs for large scale vaccination trials was a major challenge, as these molecules were extensively modified with complex linear glycan chains attached to phosphoserine residues in the polypeptide backbone, and to date, all efforts to form recombinant LPG have failed.…”

Section: Other Vaccine Candidatesmentioning

confidence: 99%

Progress in the research on diagnosis and vaccines in amebiasis

Parija

2011

Trop Parasitol

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Entameba histolytica causes amebiasis, which includes both intestinal and extraintestinal amebiasis. E. histolytica causes 34 million to 50 million symptomatic cases of amebiasis worldwide every year, causing 40 thousand to 100 thousand deaths annually. E. histolytica, the pathogenic species of amebae is indistinguishable in its cyst and trophozoite stages from those of E. moshkovskii, a free-living ameba, and E. dispar, a non-invasive ameba, by microscopy, except in cases of invasive disease, where E. histolytica trophozoite may contain ingested red blood cells, but such a finding is rarely seen. This leads to a confusing scenario for the definite identification and differentiation of E. histolytica from E. moshkovskii and E. dispar by conventional microscopy, in the diagnosis of intestinal amebiasis. The advent of molecular methods such as multiplex PCR and real time PCR have facilitated a better and accurate diagnosis of E. histolytica, E. moshkovskii, and E. dispar in stool, urine, saliva, and other specimens. Multiplex PCR for the diagnosis of amebic liver abscess, using urine and saliva as clinical specimens, has been used, and the results have been encouraging. Real-time PCR is a new and a very attractive methodology for laboratory diagnosis of amebiasis, because of its characteristics that eliminate post-PCR analysis, leading to a shorter turnaround time. Microarray-based approaches represent an attractive diagnostic tool for the detection and identification of amebae in clinical and epidemiological investigations. Development of vaccines against amebiasis is still in its infancy. However, in recent years, progress has been made in the identification of possible vaccine candidates, the route of application, and the understanding of the immune response, which is required for protection against amebiasis. Thus, it is just a matter of time, and hopefully, amebiasis vaccine for human trials will be available in the next few years.

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Identification and partial characterization of a lipophosphoglycan from a pathogenic strain of Entamoeba histolytica

Cited by 40 publications

References 19 publications

Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells

Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells

A Sequential Model of Host Cell Killing and Phagocytosis byEntamoeba histolytica

Progress in the research on diagnosis and vaccines in amebiasis

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