Iron acquisition within host cells and the pathogenicity of Leishmania.
Iron is an essential cofactor for several enzymes and metabolic pathways, in both microbes and in their eukaryotic hosts. To avoid toxicity, iron acquisition is tightly regulated. This represents a particular challenge for pathogens that reside within the endocytic pathway of mammalian cells, because endosomes and lysosomes are gradually depleted in iron by host transporters. An important player in this process is Nramp1 (Slc11a1), a proton efflux pump that translocates Fe(2+) and Mn(2+) ions from macrophage lysosomes/phagolysosomes into the cytosol. Mutations in Nramp1 cause susceptibility to infection with the bacteria Salmonella and Mycobacteria and the protozoan Leishmania, indicating that an available pool of intraphagosomal iron is critical for the intracellular survival and replication of these pathogens. Salmonella and Mycobacteria are known to express iron transporter systems that effectively compete with host transporters for iron. Until recently, however, very little was known about the molecular strategy used by Leishmania for survival in the iron-poor environment of macrophage phagolysosomes. It is now clear that intracellular residence induces Leishmania amazonensis to express LIT1, a ZIP family membrane Fe(2+) transporter that is required for intracellular growth and virulence.
Huynh
Chau
C
Section of Microbial Pathogenesis, School of Medicine, Yale University, 295 Congress avenue, New Haven, CT 06536, USA.
Andrews
Norma W
NW
D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007891:Leishmania / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008954:Models, Biological; D017494:Proton Pumps / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017262:Siderophores / Q000378:metabolism / Q000502:physiology
D017494:Proton Pumps; D015800:Protozoan Proteins; D017262:Siderophores; D007501:Iron