Action of the Major Protease from <i>Entamoeba histolytica</i> on Proteins of the Extracellular Matrix

Schulte, Werner; Scholze, Henning

doi:10.1111/j.1550-7408.1989.tb01092.x

Cited by 75 publications

(30 citation statements)

References 25 publications

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“…Collagen type I is the most common form found in a large variety of tissue and predominates in the skin (Gallop & Paz 1975). Collagen type IV and laminin are constitutive proteins of basement membranes, while collagen type V is a mediator between cells and their intracellular matrices (Schulte & Scholze 1989). In the present study the purified metallo-protease completely degraded all the 3 types of collagen and laminin under in vitro conditions (Figs.…”

Section: Discussionsupporting

confidence: 52%

Purified metallo-protease from the pathogenic haemoflagellate Cryptobia salmositica and its in vitro proteolytic activities

Zuo¹,

Woo²

1997

Dis. Aquat. Org.

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The metallo-protease (200 kDa) from Cryptobia salmositica was punfied using ionexchange chromatography and gelfiltration. The purity of the enzyme was confirmed as there was only one homogeneous band using SDS-PAGE. Under in vitro conditions the purified metallo-protease completely degraded the extracellular matrix proteins (collagen types I. [V. V and laminin) and the membrane proteins isolated from rainbow trout erythrocytes. The results confirm that the C. salmositica metallo-protease is a histolytic enzyme and it contributes to salmonid cryptobiosis and to the direct transmission of the parasite between fish.

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Section: Discussionsupporting

confidence: 52%

Purified metallo-protease from the pathogenic haemoflagellate Cryptobia salmositica and its in vitro proteolytic activities

Zuo¹,

Woo²

1997

Dis. Aquat. Org.

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“…Virulence factors such as proteases, glycosidases, and mucus secretagogues are produced by these organisms and are believed to be responsible for disruption and depletion of the mucus gel (9)(10)(11)(12). E.h. constitutively secretes at least four cysteine proteases that are involved in tissue destruction and invasive disease (22,23). The closely related noninvasive amoeba Entamoeba dispar produces significantly less cysteine protease activity than E.h. and does not express several homologous cysteine proteases that correlate with invasive disease (24,25).…”

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.

240

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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“…Three of the corresponding proteins, namely, EhCP1, EhCP2, and EhCP5, have been purified (15,30,32) and were found to account for approximately 90% of the total cysteine protease activity present in lysates of axenically cultured E. histolytica trophozoites (8). Accordingly, Northern blot analysis indicated high-level expression of ehcp1, ehcp2, and ehcp5, low-level expression of ehcp3, and no expression of ehcp4 and ehcp6 (8).…”

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confidence: 99%

The Intestinal Protozoan ParasiteEntamoeba histolyticaContains 20 Cysteine Protease Genes, of Which Only a Small Subset Is Expressed during In Vitro Cultivation

Loftus²,

et al. 2003

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Cysteine proteases are known to be important pathogenicity factors of the protozoan parasite Entamoeba histolytica. So far, a total of eight genes coding for cysteine proteases have been identified in E. histolytica, two of which are absent in the closely related nonpathogenic species E. dispar. However, present knowledge is restricted to enzymes expressed during in vitro cultivation of the parasite, which might represent only a subset of the entire repertoire. Taking advantage of the current E. histolytica genome-sequencing efforts, we analyzed databases containing more than 99% of all ameba gene sequences for the presence of cysteine protease genes. A total of 20 full-length genes was identified (including all eight genes previously reported), which show 10 to 86% sequence identity. The various genes obviously originated from two separate ancestors since they form two distinct clades. Despite cathepsin B-like substrate specificities, all of the ameba polypeptides are structurally related to cathepsin L-like enzymes. None of the previously described enzymes but 7 of the 12 newly identified proteins are unique compared to cathepsins of higher eukaryotes in that they are predicted to have transmembrane or glycosylphosphatidylinositol anchor attachment domains. Southern blot analysis revealed that orthologous sequences for all of the newly identified proteases are present in E. dispar. Interestingly, the majority of the various cysteine protease genes are not expressed in E. histolytica or E. dispar trophozoites during in vitro cultivation. Therefore, it is likely that at least some of these enzymes are required for infection of the human host and/or for completion of the parasite life cycle.Cysteine proteases (EC 3.4.22) of the papain superfamily occur in a wide range of organisms including bacteria, plants, invertebrates, and vertebrates (7). In mammals, they are well documented as intracellular enzymes involved in protein turnover within lysosomes. In addition, extracellular cysteine proteases have been implicated in various physiological and pathophysiological processes, including tumor invasion and metastasis (33,43). Cysteine proteases are important virulence factors of various infectious agents and the main proteolytic enzymes in many protozoon parasites (22,29). The protozoan Entamoeba histolytica, the causative agent of human amoebiasis, is characterized by its great capacity to destroy host tissue, leading to potentially life-threatening diseases such as ulcerative colitis or liver abscess. Convincing evidence exists that cysteine proteases are essential for E. histolytica-induced pathology. Treatment of the ameba with sublethal doses of a specific cysteine protease inhibitor or the addition of laminin, which blocks the substrate-binding pocket of cysteine proteases, greatly reduces its ability to produce liver abscesses in laboratory animals (18, 37). Likewise, liver abscess formation was totally blocked and significantly less gut inflammation and damage to the intestinal permeability barrier were obser...

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Action of the Major Protease from Entamoeba histolytica on Proteins of the Extracellular Matrix

Cited by 75 publications

References 25 publications

Purified metallo-protease from the pathogenic haemoflagellate Cryptobia salmositica and its in vitro proteolytic activities

Purified metallo-protease from the pathogenic haemoflagellate Cryptobia salmositica and its in vitro proteolytic activities

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

The Intestinal Protozoan ParasiteEntamoeba histolyticaContains 20 Cysteine Protease Genes, of Which Only a Small Subset Is Expressed during In Vitro Cultivation

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