Pathways of iron acquisition and utilization in Leishmania
Open accessAbstract
Iron is essential for many metabolic pathways, but is toxic in excess. Recent identification of the ferric iron reductase LFR1, the ferrous iron transporter LIT1, and the heme transporter LHR1 greatly advanced our understanding of how Leishmania parasites acquire iron and regulate its uptake. LFR1 and LIT1 have close orthologs in plants, and are required for Leishmania virulence. Consistent with the lack of heme biosynthesis in trypanosomatids, LHR1 and LABCG5, a protein involved in heme salvage from hemoglobin, seem essential for Leishmania survival. LFR1, LIT1 and LHR1 are upregulated under low iron availability, in agreement with the need to prevent excessive iron uptake. Future studies should clarify how Leishmania interacts with the iron homeostasis machinery of its host cell, the macrophage.
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Leishmania needs a high-affinity transporter such as LIT1 to compete effectively for Fe within its parasitophorous vacuole.
“Mutations in the lysosomal Fe efflux pump NRAMP1 confer susceptibility to Leishmania and other intravacuolar pathogens, reinforcing the conclusion that Leishmania needs a high-affinity transporter such as LIT1 to compete effectively for Fe within its parasitophorous vacuole [89].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [89]
Mutations in the lysosomal Fe efflux pump NRAMP1 confer susceptibility to Leishmania and other intravacuolar pathogens.
“Mutations in the lysosomal Fe efflux pump NRAMP1 confer susceptibility to Leishmania and other intravacuolar pathogens, reinforcing the conclusion that Leishmania needs a high-affinity transporter such as LIT1 to compete effectively for Fe within its parasitophorous vacuole [89].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [89]
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Cites
Leishmaniasis Worldwide and Global Estimates of Its Incidence
Alvar, J., Vélez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., Boer, M. D., & the WHO Leishmaniasis Control Team (2012) · PLoS ONE · doi:10.1371/journal.pone.0035671 · Cited by 5,141 · see citing works
Leishmaniasis: complexity at the host–pathogen interface
Kaye, P. M., & Scott, P. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2608 · Cited by 994 · see citing works
Iron Uptake and Transport in Plants: The Good, the Bad, and the Ionome
Morrissey, J., & Guerinot, M. L. (2009) · Chemical Reviews · doi:10.1021/cr900112r · Cited by 705 · see citing works
Mammalian iron metabolism and its control by iron regulatory proteins
Anderson, C. P., Shen, M., Eisenstein, R. S., & Leibold, E. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.05.010 · Cited by 493 · see citing works
Iron homeostasis: insights from genetics and animal models
Andrews, N. C. (2000) · Nature Reviews Genetics · doi:10.1038/35042073 · Cited by 418 · see citing works
Self-citationHaem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins
Rajagopal, A., Rao, A. U., Amigo, J., Tian, M., Upadhyay, S. K., Hall, C., Uhm, S., Mathew, M. K., Fleming, M. D., Paw, B. H., et al. (2008) · Nature · doi:10.1038/nature06934 · Cited by 316 · see citing works
Theil, E. C. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132212 · Cited by 291 · see citing works
Macrophages and Systemic Iron Homeostasis
Ganz, T. (2012) · Journal of Innate Immunity · doi:10.1159/000336423 · Cited by 281 · cited 1× · see citing works
“Because of the extensive phagocytosis of senescent red blood cells performed by macrophages from deeper organs such as the spleen [42 ], markedly different levels of iron are expected to be available within skin macrophages where cutaneous species of Leishmania replicate, when compared to liver Kupffer cells and splee…”
BackgroundIron-Dependent Self-Assembly of Recombinant Yeast Frataxin: Implications for Friedreich Ataxia
Adamec, J., Rusnak, F., Owen, W. G., Naylor, S., Benson, L. M., Gacy, A. M., & Isaya, G. (2000) · The American Journal of Human Genetics · doi:10.1086/303056 · Cited by 255 · see citing works
Andrews, N. C. (1999) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(99)00065-5 · Cited by 246 · see citing works
Self-citationWhite, C., Yuan, X., Schmidt, P. J., Bresciani, E., Samuel, T. K., Campagna, D. R., Hall, C., Bishop, K. S., Calicchio, M. L., Lapierre, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.005 · Cited by 237 · see citing works
One ring to rule them all: Trafficking of heme and heme synthesis intermediates in the metazoans
Hamza, I., & Dailey, H. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.04.009 · Cited by 237 · see citing works
Trafficking of Heme and Porphyrins in Metazoa
Severance, S., & Hamza, I. (2009) · Chemical Reviews · doi:10.1021/cr9001116 · Cited by 209 · see citing works
Antoine, J.-C., Prina, E., Lang, T., & Courret, N. (1998) · Trends in Microbiology · doi:10.1016/s0966-842x(98)01324-9 · Cited by 205 · see citing works
Determinants for the Development of Visceral Leishmaniasis Disease
McCall, L., Zhang, W., & Matlashewski, G. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003053 · Cited by 196 · see citing works
Huynh, C. D. M., Sacks, D. L., & Andrews, N. W. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060559 · Cited by 159 · see citing works
Self-citationIron uptake controls the generation of Leishmania infective forms through regulation of ROS levels
Mittra, B., Cortéz, M., Haydock, A. K., Ramasamy, G., Myler, P. J., & Andrews, N. W. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121368 · Cited by 130 · see citing works
Self-citationHeme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1
Huynh, C., Yuan, X., Miguel, D. C., Renberg, R. L., Protchenko, O., Philpott, C. C., Hamza, I., & Andrews, N. W. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002795 · Cited by 109 · see citing works
Self-citationKořený, L., Lukeš, J., & Obornı́k, M. (2009) · International Journal for Parasitology · doi:10.1016/j.ijpara.2009.11.007 · Cited by 109 · see citing works
Iron acquisition within host cells and the pathogenicity of Leishmania
Huynh, C. D. M., & Andrews, N. W. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.01095.x · Cited by 96 · see citing works
Self-citationChang, C. S., & Chang, K. P. (1985) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(85)90069-6 · Cited by 95 · see citing works
Alves, J. M. P., Voegtly, L. J., Matveyev, A. V., Lara, A. M., da Silva, F. M., Serrano, M. G., Buck, G. A., Teixeira, M. M. G., & Camargo, E. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023518 · Cited by 87 · see citing works
Hemoglobin receptor in Leishmania is a hexokinase located in the flagellar pocket
Krishnamurthy, G., Vikram, R., Singh, S. B., Patel, N., Agarwal, S., Mukhopadhyay, G., Basu, S. K., & Mukhopadhyay, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411845200 · Cited by 83 · see citing works
Das, N. K., Biswas, S., Solanki, S., & Mukhopadhyay, C. K. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2008.01241.x · Cited by 80 · see citing works
Sengupta, S., Tripathi, J., Tandon, R., Raje, M., Roy, R. P., Basu, S. K., & Mukhopadhyay, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.5.2758 · Cited by 78 · see citing works
Flannery, A. R., Huynh, C., Mittra, B., Mortara, R. A., & Andrews, N. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.229674 · Cited by 74 · see citing works
Self-citationRole of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways
Trípodi, K. E. J., Menéndez-Bravo, S., & Cricco, J. A. (2011) · Enzyme Research · doi:10.4061/2011/873230 · Cited by 69 · see citing works
Rab5‐mediated endosome–endosome fusion regulates hemoglobin endocytosis in Leishmania donovani
Singh, S., Tandon, R., Krishnamurthy, G., Vikram, R., Sharma, N., Basu, S. K., & Mukhopadhyay, A. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg557 · Cited by 63 · see citing works
Leishmania chagasi: uptake of iron bound to lactoferrin or transferrin requires an iron reductase
Wilson, M. E., Lewis, T. S., Miller, M. A., McCormick, M. L., & Britigan, B. E. (2002) · Experimental Parasitology · doi:10.1016/s0014-4894(02)00018-8 · Cited by 56 · see citing works
<i>Leishmania</i> requires Rab7-mediated degradation of endocytosed hemoglobin for their growth
Patel, N., Singh, S. B., Basu, S. K., & Mukhopadhyay, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800404105 · Cited by 56 · see citing works
Subverted transferrin trafficking in Leishmania- infected macrophages
Borges, V. M., Vannier-Santos, M. A., & de Souza, W. (1998) · Parasitology Research · doi:10.1007/s004360050493 · Cited by 52 · see citing works
Heme as a source of iron to Leishmania infantum amastigotes
Carvalho, S., Cruz, T., Santarém, N., Castro, H., Costa, V., & Tomás, A. M. (2008) · Acta Tropica · doi:10.1016/j.actatropica.2008.10.007 · Cited by 52 · see citing works
Identification and isolation of the Leishmania transferrin receptor.
Voyiatzaki, C., & Soteriadou, K. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50396-9 · Cited by 49 · see citing works
A new ATP‐binding cassette protein is involved in intracellular haem trafficking in Leishmania
Campos‐Salinas, J., Cabello‐Donayre, M., García‐Hernández, R., Pérez‐Victoria, I., Castanys, S., Gamarro, F., & Pérez-Victoria, J. M. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07531.x · Cited by 46 · see citing works
Cupello, M. P., Souza, C. F., Buchensky, C., et al. (2011) · Acta Tropica · doi:10.1016/j.actatropica.2011.08.011 · Cited by 43 · see citing works
Iron-dependent regulation of transferrin receptor expression in Trypanosoma brucei
FAST, B., KREMP, K., BOSHART, M., & STEVERDING, D. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3420691 · Cited by 43 · see citing works
Functional characterization of LIT1, the Leishmania amazonensis ferrous iron transporter
Jacques, I., Andrews, N. W., & Huynh, C. (2010) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2009.12.003 · Cited by 42 · see citing works
Self-citationCYP5122A1, a Novel Cytochrome P450 Is Essential for Survival of Leishmania donovani
Verma, S., Mehta, A., & Shaha, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025273 · Cited by 41 · see citing works
Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania
Agarwal, S., Rastogi, R., Gupta, D., Patel, N., Raje, M., & Mukhopadhyay, A. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.01.006 · Cited by 40 · see citing works
Heme binding to Leishmania mexicana amazonensis
Galbraith, R. A., & McElrath, M. J. (1988) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(88)90118-1 · Cited by 39 · see citing works
Böttger, L. H., Miller, E. P., Andresen, C., Matzanke, B. F., Küpper, F. C., & Carrano, C. J. (2012) · Journal of Experimental Botany · doi:10.1093/jxb/ers225 · Cited by 34 · see citing works
Ascorbate Peroxidase Acts As a Novel Determiner of Redox Homeostasis in Leishmania
Adak, S., & Pal, S. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4745 · Cited by 25 · see citing works
A trypanosomatid protein specifically interacts with a mammalian iron-responsive element
Meehan, H. A., Lundberg, R., & Connell, G. J. (2000) · Parasitology Research · doi:10.1007/s004360050019 · Cited by 18 · see citing works
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Research works printed but not linked: 1
- [43]McCall LI Zhang WW Matlashewski G Determinants for the development of visceral leishmaniasis disease PLoS Pathogens 2013 9 1 e1003053 23300451 PMC3536654
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Strategies of intracellular pathogens for obtaining iron from the environment
Leon-Sicairos, N., Reyes-Cortes, R., Guadrón-Llanos, A. M., Madueña-Molina, J., Leon-Sicairos, C., & Canizalez-Román, A. (2015) · BioMed Research International · doi:10.1155/2015/476534 · Cited by 51 · see citing works
“Mutations in the lysosomal Fe efflux pump NRAMP1 confer susceptibility to Leishmania and other intravacuolar pathogens, reinforcing the conclusion that Leishmania needs a highaffinity transporter such as LIT1 to compete effectively for Fe within its parasitophorous vacuole [89].”
Background
- Authors
- Flannery, A. R., Renberg, R. L., & Andrews, N. W.
- Affiliations
- University of Maryland, College Park (US)
- Corresponding author
- Andrews, Norma W
- Venue
- Current Opinion in Microbiology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 16
- Issue
- 6
- Pages
- 716-721
- ISSN
- 1369-5274 (ISSN-L)
- PMC
- PMC3842396
- OpenAlex
- W2004248893
- Cited by
- 50
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 2
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM064625)
- National Institute of Allergy and Infectious Diseases (R01AI067979, R37AI034867, T32AI089621)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Keywords
- Leishmania, iron acquisition, iron homeostasis, hemoglobin, trypanosomatids, parasite virulence, macrophages, host-parasite interactions
- MeSH terms
- Homeostasis, Iron, Leishmania, Metabolic Networks and Pathways
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