title: Use and endocytosis of iron-containing proteins by Entamoeba histolytica trophozoites.
abstract: Iron is essential for nearly all organisms; in mammals, it is part of proteins such as haemoglobin, and it is captured by transferrin and lactoferrin. Transferrin is present in serum, and lactoferrin is secreted by the mucosa and by neutrophils at infection sites, as a host iron-withholding response, sequestering iron away from invading microorganisms. Additionally, all cells contain ferritin, which sequesters iron when its intracellular levels are increased, detoxifying and preventing damage. Liver ferritin contains 50% of iron corporal reserves. During evolution, pathogens have evolved diverse strategies to obtain iron from their hosts in order to survive. The protozoan Entamoeba histolytica invades the intestinal mucosa, causing dysentery, and the trophozoites often travel to the liver producing hepatic abscesses; thus, intestine and liver proteins could be important iron supplies for E. histolytica. We found that E. histolytica trophozoites can grow in both ferrous and ferric iron, and that they can use haemoglobin, holo-transferrin, holo-lactoferrin, and ferritin as in vitro iron sources. These proteins supported the amoeba growth throughout consecutive passages, similarly to ferric citrate. By confocal microscopy and immunoblotting, iron-binding proteins were observed specifically bound to the amoeba surface, and they were endocytosed, trafficked through the endosomal/lysosomal route, and degraded by neutral and acidic cysteine-proteases. Transferrin and ferritin were mainly internalized through clathrin-coated vesicles, and holo-lactoferrin was mainly internalized by caveola-like structures. In contrast, apo-lactoferrin bound to membrane lipids and cholesterol, inducing cell death. The results suggest that in vivo trophozoites secrete products that can destroy enterocytes, erythrocytes, and hepatocytes, releasing transferrin, haemoglobin, ferritin, and other iron-containing proteins, which, together with lactoferrin derived from neutrophils and acinar cells, could be used as abundant iron supplies by amoebas.
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Mexico, DF 07000, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Soto
authors.forename: Nidia
authors.initials: N
authors.lastname: León-Sicairos
authors.forename: Magda
authors.initials: M
authors.lastname: Reyes-López
authors.forename: Jesús
authors.initials: J
authors.lastname: Serrano-Luna
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ordaz-Pichardo
authors.forename: Carolina
authors.initials: C
authors.lastname: Piña-Vázquez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ortiz-Estrada
authors.forename: Mireya
authors.initials: M
authors.lastname: de la Garza
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity; D004705:Endocytosis; D004748:Entamoeba histolytica / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D004749:Entamoebiasis / Q000378:metabolism* / Q000382:microbiology / Q000469:parasitology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D053058:Trophozoites / Q000166:cytology / Q000502:physiology*; D014774:Virulence
chemical_list: D033862:Iron-Binding Proteins; D007501:Iron