Pore-forming peptide of pathogenic Entamoeba histolytica.

Leippe, Matthias; Ebel, Sebastian; Schoenberger, Oeyvind L.; Horstmann, Rolf D.; Müller‐Eberhard, Hans J.

doi:10.1073/pnas.88.17.7659

Cited by 192 publications

(139 citation statements)

References 40 publications

(35 reference statements)

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“…Amoebapore was purified from pathogenic E. histolytica strain HM-1:IMSS essentially as described [5]. Final purification was achieved by reverse-phase high-performance liquid chromatography using an Aquapore Butyl300 column (2.1 x 220 mm; Brownlee) connected to a 130 A separation system (Applied biosystems).…”

Section: Purt$cation Of Amoebaporementioning

confidence: 99%

“…This is reflected by selective binding of many of such molecules to negatively charged phospholipids, and by their increased activity at low pH ([11,13] and references therein). Likewise, amoebapore was found to insert preferentially in liposomes composed of acidic phospholipids and to be optimally active at pH 5.2 [5]. The peptide contains nine positively charged residues that might be crucial for activity, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…The primary candidate for mediating the extraordinary cytolytic activity of E. rhistolytica is a peptide that forms ion channels in phospholipid membranes (for review see [4]). The peptide, named amoebapore, was purified from amoebic extracts [5] and its primary and secondary structure elucidated [6]. Amoebapore consists of 77 amino acid residues and has an all-a-helical conformation.…”

Section: Introductionmentioning

confidence: 99%

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Pore‐forming peptide of Entamoeba histolytica significance of positively charged amino acid residues for its mode of action

Andrä

Leippe

1994

FEBS Letters

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Amoebapore is a 77-residue pore-forming peptide from Entamoeba histolytica with antibacterial and cytolytic properties. It contains eight lysine residues and one histidine residue. Chemical modifications of amoebapore with various reagents affecting either both types of cationic residues or lysine and histidine residues separately resulted in virtually complete loss of pore-forming activity. The activity was restored by reversal of modifications. Whereas amoebapore was no longer capable of binding to phospholipid vesicles when its Iysine residues were modified, the modification of the single histidine primarily affected oligomerization of the peptide upon membrane association.

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Section: Purt$cation Of Amoebaporementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pore‐forming peptide of Entamoeba histolytica significance of positively charged amino acid residues for its mode of action

Andrä

Leippe

1994

FEBS Letters

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“…A third mechanism involving direct T cell antimicrobial activity was suggested from studies identifying granulysin (1) in cytoplasmic granules of cytolytic T cells (2,3). Granulysin is a member of the saposin-like protein (SAPLIP) 3 family, including amoebapores, antimicrobial proteins that amoebas use to prevent growth of phagocytosed bacteria (4). Granulysin itself has a broad spectrum of antimicrobial activity, killing bacteria, fungi, and parasites, but is poorly lytic against cells of the monocyte/ macrophage lineage (5).…”

mentioning

confidence: 99%

Granulysin, a T Cell Product, Kills Bacteria by Altering Membrane Permeability

Ernst

Thoma-Uszynski

Teitelbaum

et al. 2000

The Journal of Immunology

196

172

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Granulysin, a protein located in the acidic granules of human NK cells and cytotoxic T cells, has antimicrobial activity against a broad spectrum of microbial pathogens. A predicted model generated from the nuclear magnetic resonance structure of a related protein, NK lysin, suggested that granulysin contains a four α helical bundle motif, with the α helices enriched for positively charged amino acids, including arginine and lysine residues. Denaturation of the polypeptide reduced the α helical content from 49 to 18% resulted in complete inhibition of antimicrobial activity. Chemical modification of the arginine, but not the lysine, residues also blocked the antimicrobial activity and interfered with the ability of granulysin to adhere to Escherichia coli and Mycobacterium tuberculosis. Granulysin increased the permeability of bacterial membranes, as judged by its ability to allow access of cytosolic β-galactosidase to its impermeant substrate. By electron microscopy, granulysin triggered fluid accumulation in the periplasm of M. tuberculosis, consistent with osmotic perturbation. These data suggest that the ability of granulysin to kill microbial pathogens is dependent on direct interaction with the microbial cell wall and/or membrane, leading to increased permeability and lysis.

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“…D iscovered in 1982 (Lynch et al, 1982;Young et al, 1982), the amoebapores are membraneinteracting proteins which display pore-forming activity toward liposomes (Leippe et al, 1991). They have antibacterial activity (Leippe et al, 1994a) and are cytotoxic to human cell lines in vitro (Leippe et al, 1994b).…”

Section: Amoebapores and The Saposin-like Familymentioning

confidence: 99%

Trophozoites ofEntamoeba histolyticaepigenetically silenced in several genes are virulence-attenuated

2008

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Summary :The human intestinal parasite Entamoeba histolytica causes amoebic colitis and amoebic liver abscesses. Three classes of amoebic molecules have been identified as the major virulence factors, the Gal/GalNAc inhibitable lectin that mediates adherence to mammalian cells, the amoebapores which cause the formation of membrane ion channels in the target cells and the cysteine proteinases which degrade the matrix proteins, the intestinal mucus and secretory IgA. Transcriptional silencing of the amoebapore (Ehap-a) gene occurred after transfection of trophozoites with a plasmid containing a segment of the 5' upstream region of the gene. Transcriptional silencing of the Ehap-a gene continued even after the removal of the plasmid and the cloned amoebae were termed G3. Transfection of G3 trophozoites with a plasmid construct containing the cysteine proteinase (EhCP-5) gene and the light subunit of the Gal-lectin (Ehlgl1) gene, each under the 5' upstream sequences of the amoebapore gene, caused the simultaneous epigenetic silencing of expression of these two genes. The resulting trophozoites, termed RB-9, were cured from the plasmid and they do not express the three types of virulent genes. The RB-9 amoeba are virulence attenuated and are incapable of killing mammalian cells, they can not induce the formation of liver abscesses and they do not cause ulcerations in the cecum of experimental animals. The gene-silenced amoebae express the same surface antigens which are present in virulent strains and following intra peritoneal inoculation of live trophozoites into hamsters they evoked a protective immune response. Further studies are needed to find out if RB-9 trophozoites could be used for vaccination against amoebaisis.KEY WORDS : Entamoeba histolytica, RB-9 trophozoite, virulence.

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Pore-forming peptide of pathogenic Entamoeba histolytica.

Cited by 192 publications

References 40 publications

Pore‐forming peptide of Entamoeba histolytica significance of positively charged amino acid residues for its mode of action

Pore‐forming peptide of Entamoeba histolytica significance of positively charged amino acid residues for its mode of action

Granulysin, a T Cell Product, Kills Bacteria by Altering Membrane Permeability

Trophozoites ofEntamoeba histolyticaepigenetically silenced in several genes are virulence-attenuated

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