Host tissue destruction by Entamoeba histolytica: molecules mediating adhesion, cytolysis, and proteolysis

Horstmann, Rolf D.; Leippe, Matthias; Tannich, Egbert

doi:10.1590/s0074-02761992000900007

Cited by 13 publications

(6 citation statements)

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“…Cysteine protease activity is necessary for the trophozoites to traverse a colonic mucus barrier before cell cytolysis (8,16). In addition, the proteases are necessary for the parasite to disrupt the epithelial cell monolayers in vitro (15), to disseminate through host tissue (26), and to cause liver abscesses (27,28). The mechanism by which the parasite disrupts and penetrates the mucin polymeric network was previously unknown, but recent evidence suggests that the amoeba disrupts the MUC2 polymers (8).…”

Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel

Lidell

Moncada

Chadee

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

237

182

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In order for the protozoan parasite Entamoeba histolytica (E.h.) to cause invasive intestinal and extraintestinal infection, which leads to significant morbidity and mortality, it must disrupt the protective mucus layer by a previously unknown mechanism. We hypothesized that cysteine proteases secreted from the amoeba disrupt the mucin polymeric network, thereby overcoming the protective mucus barrier. The MUC2 mucin is the major structural component of the colonic mucus gel. Heavily O-glycosylated and protease-resistant mucin domains characterize gel-forming mucins. Their N-and C-terminal cysteine-rich domains are involved in mucin polymerization, and these domains are likely to be targeted by proteases because they are less glycosylated, thereby exposing their peptide chains. By treating recombinant cysteine-rich domains of MUC2 with proteases from E.h. trophozoites, we showed that the C-terminal domain was specifically targeted at two sites by cysteine proteases, whereas the N-terminal domain was resistant to proteolysis. The major cleavage site is predicted to depolymerize the MUC2 polymers, thereby disrupting the protective mucus gel. The ability of the cysteine proteases to dissolve mucus gels was confirmed by treating mucins from a MUC2-producing cell line with amoeba proteases. These findings suggest a major role for E.h. cysteine proteases in overcoming the protective mucus barrier in the pathogenesis of invasive amoebiasis. In this report, we identify a specific cleavage mechanism used by an enteric pathogen to disrupt the polymeric nature of the mucin gel.colon ͉ parasite

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Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel

Lidell

Moncada

Chadee

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

237

182

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“…Nevertheless, one can assume that epithelial cell apoptosis promotes intestinal barrier leakage and thus facilitates invasion. Amoebapores are pathogenic factors known to be involved in epithelial cell lysis (Horstmann et al 1992; Andra et al 2003). The pathogenicity of the G3 strain [which lacks amoebapore-A (Bracha et al 2003)] has been investigated in human colon explants.…”

Section: Interplay Between the Human Colon And The Parasite During Timentioning

confidence: 99%

Crosstalk between Entamoeba histolytica and the human intestinal tract during amoebiasis

et al. 2017

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The protozoan parasite Entamoeba histolytica is the microbial agent of amoebiasis - an infection that is endemic worldwide and is associated with high morbidity and mortality rates. As the disease develops, virulent E. histolytica deplete the mucus layer, interact with the intestinal epithelium, and then degrade the colonic mucosa and disrupt the extracellular matrix (ECM). Our research demonstrated that virulent parasites with an invasive phenotype display rapid, highly specific changes in their transcriptome (notably for essential factors involved in carbohydrate metabolism and the processing of glycosylated residues). Moreover, combined activation of parasite and host lytic enzymes leads to the destruction of the intestinal parenchyma. Together, these enzymes degrade the mucus layer and the ECM, and trigger the inflammatory response essential to the development of amoebiasis.

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“…Several unicellular parasites have developed various pore-forming proteins, such as the amoebapores in Entamoeba histolytica (Lynch et al 1982;Young et al 1982;Horstmann et al 1992), leishporin of Leishmania (Noronha et al 1994(Noronha et al , 1996, TC-tox in T. cruzi (Andrews 1990; Andrews et al 1990) and lysterilysin-O in Lysteria monocytogenes bacteria (Bhakdi and TranunJensen 1988;Bielecki et al 1990). The aim of our study was to analyze, by electron microscopy, the interaction of T. rangeli with the salivary glands of experimentally infected Rhodnius domesticus, and characterize a possible pore-forming protein that could be used by the parasites to reach the salivary gland lumen.…”

Section: Introductionmentioning

confidence: 99%

Penetration of the salivary glands of Rhodnius domesticus Neiva & Pinto, 1923 (Hemiptera: Reduviidae) by Trypanosoma rangeli Tejera, 1920 (Protozoa: Kinetoplastida)

et al. 2005

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Penetration of the heteroxenous protozoan Trypanosoma rangeli into the salivary glands of its invertebrate host Rhodnius domesticus has been investigated here using different approaches. Electron microscopy showed that epimastigotes coming from the insect hemocoel cross the basal lamina that surrounds the salivary glands and penetrate through the gland cells cytoplasm. After reaching the gland lumen, epimastigote forms remain adhered to the gland cell microvilli by their flagella, while metacyclic trypomastigotes are found swimming free in the saliva. Analysis by flow cytometry, western blotting and hemolytic activity allowed to demonstrate the presence in T. rangeli of a hemolytic molecule with antigenic cross-reactivity with murine perforin, which could be used by the parasites to reach the salivary gland lumen. This molecule, which we named as rangelysin, has 120 kDa molecular weight, is able to induce hemolysis only in acidic pH, and is produced by both trypomastigote and epimastigote forms.

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Host tissue destruction by Entamoeba histolytica: molecules mediating adhesion, cytolysis, and proteolysis

Cited by 13 publications

References 0 publications

Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel

Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel

Crosstalk between Entamoeba histolytica and the human intestinal tract during amoebiasis

Penetration of the salivary glands of Rhodnius domesticus Neiva & Pinto, 1923 (Hemiptera: Reduviidae) by Trypanosoma rangeli Tejera, 1920 (Protozoa: Kinetoplastida)

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