title: The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue.
abstract: Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs' proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.
authors.affiliation: 1] Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, 75724 Paris Cedex 15, France [2] INSERM U786, 75724 Paris Cedex 15, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Thibeaux
authors.affiliation: Institut Pasteur, Unité d'Histophatologie Humaine et modèles animaux, 75724 Paris Cedex 15, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Avé
authors.affiliation: Hôpital Foch, Service Anatomopathologie, 92151 Suresnes, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bernier
authors.affiliation: Hôpital Foch, Service Anatomopathologie, 92151 Suresnes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Morcelet
authors.affiliation: Hôpital Foch, Chirurgie générale et digestive, 92151 Suresnes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Frileux
authors.affiliation: 1] Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, 75724 Paris Cedex 15, France [2] INSERM U786, 75724 Paris Cedex 15, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillén
authors.affiliation: 1] Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, 75724 Paris Cedex 15, France [2] INSERM U786, 75724 Paris Cedex 15, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Labruyère
mesh_terms: D003106:Colon / Q000378:metabolism* / Q000473:pathology; D057056:Cysteine Proteases / Q000235:genetics* / Q000378:metabolism; D004748:Entamoeba histolytica / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004792:Enzyme Precursors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D057056:Cysteine Proteases; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; C048047:prostromelysin; D020781:Matrix Metalloproteinase 1