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, becaus...

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Published inCellular microbiology Vol. 10; no. 2; pp. 293 - 300
Main Authors Huynh, Chau, Andrews, Norma W
Format Journal Article
LanguageEnglish
Published Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.02.2008
Blackwell Publishing Ltd
Hindawi Limited
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Abstract 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 Fe²⁺ and Mn²⁺ 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 Fe²⁺ transporter that is required for intracellular growth and virulence.
AbstractList 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 Fe2+ and Mn2+ 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 Fe2+ transporter that is required for intracellular growth and virulence.
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 Fe²⁺ and Mn²⁺ 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 Fe²⁺ transporter that is required for intracellular growth and virulence.
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.
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.
Summary 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 Fe2+ and Mn2+ 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 Fe2+ transporter that is required for intracellular growth and virulence.
Author Andrews, Norma W
Huynh, Chau
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Snippet Iron is an essential cofactor for several enzymes and metabolic pathways, in both microbes and in their eukaryotic hosts. To avoid toxicity, iron acquisition...
Summary Iron is an essential cofactor for several enzymes and metabolic pathways, in both microbes and in their eukaryotic hosts. To avoid toxicity, iron...
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wiley
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StartPage 293
SubjectTerms Animals
Biological Transport - genetics
Biological Transport - physiology
Cell Membrane - metabolism
Iron - metabolism
Leishmania - genetics
Leishmania - metabolism
Leishmania - pathogenicity
Models, Biological
Proton Pumps - genetics
Proton Pumps - metabolism
Proton Pumps - physiology
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Protozoan Proteins - physiology
Siderophores - metabolism
Siderophores - physiology
Title Iron acquisition within host cells and the pathogenicity of Leishmania
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1462-5822.2007.01095.x
https://www.ncbi.nlm.nih.gov/pubmed/18070118
https://www.proquest.com/docview/203563047
https://search.proquest.com/docview/70203180
https://pubmed.ncbi.nlm.nih.gov/PMC2366998
Volume 10
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