Ferritin as an Iron Source for Pathogens (pp.1-46)
Authors: (Fernando López-Soto, Carolina Piña-Vázquez, Jesús Serrano-Luna, Carmen Candia-Plata, Mireya de la Garza, Laboratorio de Bioquímica de Proteínas, Departamento de Medicina y Ciencias de la Salud, Universidad de Sonora, Hermosillo, Sonora, México)
Abstract: In this chapter we analyze the interaction between the host ferritin and pathogenic microorganisms, since this ferric protein can be used by invaders for their growth and, thus, colonization and invasion of tissues, causing disease. Iron is an essential nutrient for all living beings; however, this metal is toxic and must be captured by proteins, among them ferritin, the great intracellular storage of iron in the body. Pathogens living inside humans also need the vital iron; therefore, the iron availability in body tissues plays a crucial role in the host-pathogen relationship. In general, microorganisms living within a mammal have
evolved several mechanisms to scavenge iron from the host iron-containing proteins; these mechanisms have been considered to be important virulence factors. Pathogens able to destroy cells and tissues can have easy access to ferritin and make use of its iron. Due to the high amount of iron atoms that ferritin is able to capture, this protein is really a remarkable iron source for every intracellular pathogen. In the literature, there are only a few reports about pathogens using ferritin as an iron source, but this is an exciting growing field of research. Each pathogen has developed its own manner to obtain iron from ferritin: for instance, the bacterium Neisseria meningitidis triggers the host ferritin redistribution from cytosol to lysosomes within infected epithelial cells and accelerates the ferritin degradation by lysosomal proteases, thus providing the necessary iron for its own existence. On the other hand, in spite of being ferritin a stable supramolecular complex, Burkholderia cenocepacia secretes serine-proteases that degrade ferritin. Some strains of Escherichia coli and Mycobacterium secrete siderophores, ultra-high affinity iron-binding compounds able to confiscate iron to host ferritin. Another mechanism to get ferritin iron is the reported in Listeria monocytogenes and the mucosal pathogenic fungus Candida albicans, which use surface reductases to acquire iron from ferritin. In parasitic protozoa, there are practically no reports about the utilization of ferritin as a sole iron source. Trichomonas vaginalis uses ferritin iron but the mechanism by which it uptakes iron from this protein is still unknown. Recently, we reported that Entamoeba histolytica trophozoites endocytose ferritin by clathrin-coated pits and degrade this protein by means of specific cysteine proteases in the endosome/lysosome pathway. Concluding, pathogenic microorganisms capable of removing and acquiring iron from ferritin can obtain a plentiful source of this crucial metal to survive, colonize and invade the host.
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