Acquisition of iron from transferrin and lactoferrin by the protozoan Leishmania chagasi
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Leishmania chagasi, the cause of South American visceral leishmaniasis, requires iron for its growth. However, the extent to which different iron sources can be utilized by the parasite is not known. To address this question, we studied acquisition of iron from lactoferrin and transferrin by the extracellular promastigote form of L. chagasi during growth in vitro. A promastigote growth medium based on minimal essential medium supplemented with iron-depleted serum supported promastigote growth only after the addition of exogenous iron. The addition of 8 microM iron chelated to lactoferrin or hemin resulted in normal promastigote growth. Ferritransferrin also supported promastigote growth, but only after a considerable lag. Promastigotes grown in all three iron sources generated similar amounts of hydroxyl radical upon exposure to hydrogen peroxide, indicating that none of these protected parasites against generation of this toxic radical. Promastigotes were able to take up 59Fe chelated to either transferrin or lactoferrin, although uptake from 59Fe-lactoferrin occurred more rapidly. 59Fe uptake from either 59Fe-transferrin or 59Fe-lactoferrin was inhibited by a 10-fold excess of unlabeled ferrilactoferrin, ferritransferrin, apolactoferrin, apotransferrin, or iron nitrilotriacetate but not ferritin or bovine serum albumin. There was no evidence for a role for parasite-derived siderophores or proteolytic cleavage of ferritransferrin or ferrilactoferrin in the acquisition of iron by promastigotes. Thus, L. chagasi promastigotes can acquire iron from hemin, ferrilactoferrin, or ferritransferrin. This capacity to utilize several iron sources may contribute to the organism's ability to survive in the diverse environments it encounters in the insect and mammalian hosts.
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Intracellular L. amazonensis possesses a ferric reductase, LFR1, which provides soluble Fe2+ for transport across the parasite plasma membrane by LIT1.
“Furthermore, intracellular L. amazonensis also possesses a ferric reductase, the Leismania ferric iron reductase 1 (LFR1), which provides soluble Fe2+ for transport across the parasite plasma membrane by the ferrous iron transporter, Leishmania iron transporter 1 (LIT1) [83, 84].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [84]
Cites
FERRITIN: STRUCTURE, GENE REGULATION, AND CELLULAR FUNCTION IN ANIMALS, PLANTS, AND MICROORGANISMS
Theil, E. C. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.001445 · Cited by 1,337 · see citing works
Neilands, J. B. (1981) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.50.070181.003435 · Cited by 1,241 · see citing works
Microbial Envelope Proteins Related to Iron
Neilands, J. B. (1982) · Annual Review of Microbiology · doi:10.1146/annurev.mi.36.100182.001441 · Cited by 559 · see citing works
Role of Iron in Bacterial Infection
Bullen, J. J., Rogers, H. J., & Griffiths, E. (1978) · Modern aspects of electrochemistry · doi:10.1007/978-3-642-66956-9_1 · Cited by 494 · see citing works
Transferrins and Heme-Compounds as Iron Sources for Pathogenic Bacteria
Otto, B. R., Vught, A. M. J. J. V.-V., & MacLaren, D. M. (1992) · Critical Reviews in Microbiology · doi:10.3109/10408419209114559 · Cited by 394 · see citing works
Siderophore activity of pyoverdin for Pseudomonas aeruginosa
Cox, C. D., & Adams, P. (1985) · Infection and Immunity · doi:10.1128/iai.48.1.130-138.1985 · Cited by 272 · see citing works
Susceptibility of leishmania to oxygen intermediates and killing by normal macrophages
Murray, H. W. (1981) · The Journal of Experimental Medicine · doi:10.1084/jem.153.5.1302 · Cited by 261 · see citing works
Metacyclogenesis is a major determinant of Leishmania promastigote virulence and attenuation
da Silva, R., & Sacks, D. L. (1987) · Infection and Immunity · doi:10.1128/iai.55.11.2802-2806.1987 · Cited by 247 · see citing works
Stage-Specific Adhesion of Leishmania Promastigotes to the Sandfly Midgut
Pimenta, P. F. P., Turco, S. J., McConville, M. J., Lawyer, P. G., Perkins, P. V., & Sacks, D. L. (1992) · Science · doi:10.1126/science.1615326 · Cited by 236 · see citing works
Development of Infective Stage Leishmania Promastigotes within Phlebotomine Sand Flies
Sacks, D. L., & Perkins, P. V. (1985) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1985.34.456 · Cited by 176 · see citing works
Murray, H. W., & Cartelli, D. M. (1983) · Journal of Clinical Investigation · doi:10.1172/jci110972 · Cited by 173 · see citing works
Britigan, B. E., Hayek, M. B., Doebbeling, B. N., & Fick, R. B. (1993) · Infection and Immunity · doi:10.1128/iai.61.12.5049-5055.1993 · Cited by 156 · see citing works
Self-citationMechanism of lethal effect of human serum upon Leishmania donovani.
Pearson, R. D., & Steigbigel, R. T. (1980) · The Journal of Immunology · doi:10.4049/jimmunol.125.5.2195 · Cited by 139 · see citing works
Identification of the transferrin- and lactoferrin-binding proteins in Haemophilus influenzae
Schryvers, A. B. (1989) · Journal of Medical Microbiology · doi:10.1099/00222615-29-2-121 · Cited by 130 · see citing works
Bartfeld, N. S., & Law, J. H. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45794-8 · Cited by 129 · see citing works
Identification of a large pre-lysosomal compartment in the pathogenic protozoon Trypanosoma cruzi
Soares, M. J., Souto-Padrón, T. C. B. S., & de Souza, W. (1992) · Journal of Cell Science · doi:10.1242/jcs.102.1.157 · Cited by 129 · see citing works
Schell, D., Evers, R., Preis, D., Ziegelbauer, K. B., Kiefer, H., Lottspeich, F., Cornelissen, A. W. C. A., & Overath, P. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb08045.x · Cited by 123 · see citing works
Lehker, M. W., Arroyo, R., & Alderete, J. F. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.2.311 · Cited by 118 · see citing works
Ogunnariwo, J. A., & Schryvers, A. B. (1990) · Infection and Immunity · doi:10.1128/iai.58.7.2091-2097.1990 · Cited by 115 · see citing works
Zarley, J. H., Britigan, B. E., & Wilson, M. E. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115461 · Cited by 112 · see citing works
Self-citationJamroz, R. C., Gasdaska, J. R., Bradfield, J. Y., & Law, J. H. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.4.1320 · Cited by 108 · see citing works
Blanton, K. J., Biswas, G. D., Tsai, J., Adams, J., Dyer, D. W., Davis, S. M., Koch, G. G., Sen, P. K., & Sparling, P. F. (1990) · Journal of Bacteriology · doi:10.1128/jb.172.9.5225-5235.1990 · Cited by 102 · see citing works
Positive transcriptional regulation of an iron-regulated virulence gene in Vibrio cholerae.
Goldberg, M. B., Boyko, S. A., & Calderwood, S. B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1125 · Cited by 96 · see citing works
Haldar, K., Henderson, C. L., & Cross, G. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.22.8565 · Cited by 96 · see citing works
Chang, C. S., & Chang, K. P. (1985) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(85)90069-6 · Cited by 95 · see citing works
Receptors for transferrin in pathogenic bacteria are specific for the host's protein
Schryvers, A. B., & Gonzalez, G. C. (1990) · Canadian Journal of Microbiology · doi:10.1139/m90-026 · Cited by 92 · see citing works
Iron acquisition and hemolysin production by Campylobacter jejuni
Pickett, C. L., Auffenberg, T., Pesci, E. C., Sheen, V. L., & Jusuf, S. S. (1992) · Infection and Immunity · doi:10.1128/iai.60.9.3872-3877.1992 · Cited by 91 · see citing works
Döring, G., Pfestorf, M., Botzenhart, K., & Abdallah, M. A. (1988) · Infection and Immunity · doi:10.1128/iai.56.1.291-293.1988 · Cited by 80 · see citing works
Differential survival of Leishmania donovani amastigotes in human monocytes.
Pearson, R. D., Harcus, J. L., Roberts, D., & Donowitz, G. R. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.131.4.1994 · Cited by 75 · see citing works
The critical role of iron in some clinical infections
Bullen, J. J., Ward, C., & Rogers, H. J. (1991) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf01975810 · Cited by 72 · see citing works
Iron and ferritin contents and distribution in human alveolar macrophages.
McGowan, S. E., & Sa, H. (1988) · PubMed · Cited by 71 · see citing works
Menozzi, F. D., Gantiez, C., & Locht, C. (1991) · Infection and Immunity · doi:10.1128/iai.59.11.3982-3988.1991 · Cited by 70 · see citing works
Acquisition of iron by Legionella pneumophila: role of iron reductase
Johnson, W., Varner, L., & Poch, M. (1991) · Infection and Immunity · doi:10.1128/iai.59.7.2376-2381.1991 · Cited by 64 · see citing works
Dai, J., Lee, Y. S., & Wong, H. (1992) · Infection and Immunity · doi:10.1128/iai.60.7.2952-2956.1992 · Cited by 61 · see citing works
Trypanosoma cruzi receptors for human transferrin and their role
LIMA, M., & VILLALTA, F. (1990) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(90)90027-j · Cited by 58 · cited 1× · see citing works
“Proteins capable of binding transferrin have also been isolated from other members of the Trypanosomatidae family of protozoa, including T brucei (41) and Trypanosoma cruzi (24, 44).”
BackgroundIdentification 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
Ford, S. P., Cooper, R. A., Evans, R. W., Hider, R. C., & WILLIAMS, P. H. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14473.x · Cited by 39 · 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
Yu, R. H., Gray‐Owen, S. D., Ogunnariwo, J. A., & Schryvers, A. B. (1992) · Infection and Immunity · doi:10.1128/iai.60.7.2992-2994.1992 · Cited by 36 · see citing works
Evidence for in vivo expression of transferrin-binding proteins in Haemophilus influenzae type b
Holland, J., Langford, P. R., Towner, K. J., & Williams, P. M. (1992) · Infection and Immunity · doi:10.1128/iai.60.7.2986-2991.1992 · Cited by 35 · see citing works
Evidence of transferrin binding sites on the surface of Leishmania promastigotes.
Voyiatzaki, C., & Soteriadou, K. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45716-x · Cited by 34 · see citing works
Inability to detect transferrin receptors on P. falciparum parasitized red cells
Pollack, S., & Schnelle, V. (1988) · British Journal of Haematology · doi:10.1111/j.1365-2141.1988.tb04190.x · Cited by 34 · see citing works
Human lactoferrin binding in clinical isolates of Staphylococcus aureus
Naidu, A. S., Międzobrodzki, J., Musser, J. M., Rosdahl, V. T., HEDSTRÖM, S. Å., & Forsgren, A. (1991) · Journal of Medical Microbiology · doi:10.1099/00222615-34-6-323 · Cited by 34 · see citing works
Laboratory cultivation and maintenance of Leishmania.
Chang, K. P., Hendricks, L. D., & Bray, R. S. (1985) · Cited by 32 · see citing works
Specific binding of lactoferrin to Aeromonas hydrophila
Kishore, A. R., Erdei, J., Naidu, S. S., Falsen, E., Forsgren, A., & Naidu, A. S. (1991) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1991.tb04399.x · Cited by 30 · see citing works
Characterization of an insect ferritin subunit synthesized in a cell-free system
Ketola-Pirie, C. A. (1990) · Biochemistry and Cell Biology · doi:10.1139/o90-148 · Cited by 13 · see citing works
Lactoferrin binding properties of Vibrio cholerae.
Ascencio, F., Ljungh, Å., & Wadström, T. (1992) · PubMed · Cited by 7 · see citing works
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Acquisition, Transport, and Storage of Iron by Pathogenic Fungi
Howard, D. H. (1999) · Clinical Microbiology Reviews · doi:10.1128/cmr.12.3.394 · Cited by 260 · see citing works
“No fungus has been reported to be able to remove iron from transferrin or lactoferrin, although several bacteria and some animal parasites can do so (79, 97).”
BackgroundGallium Disrupts Iron Metabolism of Mycobacteria Residing within Human Macrophages
Olakanmi, O., Britigan, B. E., & Schlesinger, L. S. (2000) · Infection and Immunity · doi:10.1128/iai.68.10.5619-5627.2000 · Cited by 220 · see citing works
Self-citationGruden, Š., & Ulrih, N. P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011264 · Cited by 187 · see citing works
“Iron uptake from transferrin and lactoferrin has also been demonstrated for Trichomonas vaginalis [216], Trichomonas foetus [218], and Leishmania chagasi [219]; however, in the last case, other possible mechanism of iron sequestrating have been proposed [220].”
BackgroundHuynh, 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
“Although Leishmania also appears capable of acquiring Fe3+ complexed with lactoferrin or transferrin (12, 14), the existence of a specifi c receptor-based uptake mechanism in these parasites has not been confi rmed (6).”
BackgroundKelly, P. H., Bahr, S. M., Serafim, T. D., Ajami, N. J., Petrosino, J. F., Meneses, C., Kirby, J. R., Valenzuela, J. G., Kamhawi, S., & Wilson, M. E. (2017) · mBio · doi:10.1128/mbio.01121-16 · Cited by 152 · see citing works
Self-citationCrusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence
Šuťák, R., Lesuisse, E., Tachezy, J., & Richardson, D. R. (2008) · Trends in Microbiology · doi:10.1016/j.tim.2008.03.005 · Cited by 142 · see citing works
Milk-derived proteins and peptides of potential therapeutic and nutritive value.
Zimecki, M., & Kruzel, M. L. (2007) · PubMed · Cited by 117 · see citing works
Mehta, A. K., & Shaha, C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.01.024 · Cited by 118 · see citing works
“are hemoflagellate parasites that require iron for growth of both the mammalian and the insect stages [18,19]; however, there is little information regarding the role of iron during drug-induced death.”
BackgroundCaccavo, D., Pellegrino, N. M., Altamura, M., Rigon, A., Amati, L., Amoroso, A., & Jirillo, E. (2002) · Journal of Endotoxin Research · doi:10.1179/096805102125001000 · Cited by 124 · see citing works
The Role of Iron In Protozoan and Fungal Infectious Diseases
Weinberg, E. D. (1999) · Journal of Eukaryotic Microbiology · doi:10.1111/j.1550-7408.1999.tb05119.x · Cited by 115 · 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
“A study using Leishmania chagasi showed that soluble molecules secreted by the parasites are not capable of removing iron from lactoferrin or transferrin (Wilson et al., 1994).”
BackgroundIron metabolism in trypanosomatids, and its crucial role in infection
Taylor, M. C., & Kelly, J. M. (2010) · Parasitology · doi:10.1017/s0031182009991880 · Cited by 95 · see citing works
“Binding of transferrin and lactoferrin by promastigotes of L. chagasi has been shown, although the receptors responsible have not been characterized at the gene level (Wilson et al. 1994, 2002).”
BackgroundIn vitro activity and mode of action of phenolic compounds on Leishmania donovani
Antwi, C. A., Amisigo, C. M., Adjimani, J. P., & Gwira, T. M. (2019) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007206 · Cited by 92 · see citing works
Sen, G., Mukhopadhyay, S., Ray, M., & Biswas, T. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn053 · Cited by 93 · 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
“A previous study ruled out the possibility of a secreted iron chelator from L. chagasi promastigote (Wilson et al., 1994).”
BackgroundFlannery, 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
Iron Acquisition by Parasitic Protozoa
Wilson, M. E., & Britigan, B. E. (1998) · Parasitology Today · doi:10.1016/s0169-4758(98)01294-0 · Cited by 64 · see citing works
Self-citationSerum Stimulates Growth of and Proteinase Secretion by Aspergillus fumigatus
Gifford, A. H. T., Klippenstein, J. R., & Moore, M. M. (2002) · Infection and Immunity · doi:10.1128/iai.70.1.19-26.2002 · Cited by 62 · 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
Self-citation<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
“In addition, Leishmania can be grown in the culture medium containing hemin (34) or Hb (35), strongly indicating the possibility of generating heme from Hb degradation by the parasites emerging from our studies.”
BackgroundDynamics of sterol synthesis during development of Leishmania spp. parasites to their virulent form
Yao, C., & Wilson, M. E. (2016) · Parasites & Vectors · doi:10.1186/s13071-016-1470-0 · Cited by 56 · see citing works
Self-citationFungal Siderophores: Structure, Functions and Regulation
Das, A., Prasad, R., Srivastava, A., Giang, P. H., Bhatnagar, K., & Varma, A. K. (2007) · Springer eBooks · doi:10.1007/978-3-540-71160-5_1 · Cited by 55 · 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
“Despite the iron acquisition via human Tf (HTf) by L. chagasi promastigotes (Wilson et al. 1994) and the speci®c and saturable binding of this protein to both of the developmental forms of the parasite (Voyiatzaki and The authors dedicate this paper in honor of Prof. Carlos Chagas Filho, founder of…”
BackgroundInfluentialHeme 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
“The insect stage f the parasite can use different iron sources (Wilson et al., 1994). n the amastigote stage, the situation may be somewhat different s replication of Leishmania amazonensis within a mammalian host as shown to depend on uptake of ionic iron through the ferrous ransporter LIT (Huynh…”
BackgroundStrategies 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
Human hololactoferrin: endocytosis and use as an iron source by the parasite Entamoeba histolytica
León-Sicairos, N. M., Reyes‐López, M., Canizalez‐Román, A., Bermúdez‐Cruz, R. M., Serrano‐Luna, J., Arroyo, R., & de la Garza, M. (2005) · Microbiology · doi:10.1099/mic.0.28121-0 · Cited by 48 · see citing works
“In addition, pathogens grown in vitro require higher iron concentrations from ferric citrate, ferric nitrilotriacetate (Fe-NTA), FeSO4 and other sources than from host proteins, such as Hb, Lf and Tf (Wilson et al., 1994; Tachezy et al., 1996; Jarosik et al., 1998; Serrano-Luna et al., 1998b; Reyes-López et al., 2001).”
IRONy OF FATE: role of iron-mediated ROS in Leishmania differentiation
Mittra, B., & Andrews, N. W. (2013) · Trends in Parasitology · doi:10.1016/j.pt.2013.07.007 · Cited by 47 · see citing works
Goulet, V., Britigan, B. E., Nakayama, K., & Grenier, D. (2004) · Infection and Immunity · doi:10.1128/iai.72.8.4351-4356.2004 · Cited by 46 · see citing works
“Uptake of iron from transferrin mediated by proteolytic degradation was previously reported for Leishmania chagasi (40) and Pseudomonas pseudomallei (42).”
BackgroundSelf-citationPrevalence, severity, and pathogeneses of anemia in visceral leishmaniasis
Goto, Y., Cheng, J., Omachi, S., & Morimoto, A. (2016) · Parasitology Research · doi:10.1007/s00436-016-5313-x · Cited by 44 · see citing works
Rey-Benito, G. J., Ferro, C., & Bello, F. J. (2000) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762000000100017 · Cited by 38 · see citing works
“…and could multiply themselves, was not due to the MM/VP12 medium, but rather to some type of relationship which the parasite established with the cell, perhaps taking some growth factors or ions from it, which (such as iron) are fundamental substances for parasite preservation (Wilson et al. 1994).”
BackgroundVale-Costa, S., Gomes‐Pereira, S., Teixeira, C. M., Rosa, G. M., Rodrigues, P., Tomás, A. M., Appelberg, R., & Gomes, M. S. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002061 · Cited by 35 · see citing works
“infantum promastigotes have been shown to accumulate iron in catalytically active forms, which contribute to their sensitivity to killing by hydrogen peroxide [63,64], possibly through the Fenton reaction.”
BackgroundDysregulated Iron Homeostasis as Common Disease Etiology and Promising Therapeutic Target
Holbein, B. E., & Lehmann, C. (2023) · Antioxidants · doi:10.3390/antiox12030671 · Cited by 37 · see citing works
“Leishmania chagasi, which causes leishmaniasis, can utilize iron from transferrin, lactoferrin or heme when growing in its promastigote form, taking these up directly without deployment of iron-intercepting siderophores [56].”
BackgroundInduction, binding specificity and function of human ICOS
Beier, K. C., Hutloff, A., Dittrich, A., Heuck, C. J., Rauch, A. M., Büchner, K., Ludewig, B., Ochs, H. D., Mages, H. W., & Kroczek, R. A. (2000) · European Journal of Immunology · doi:10.1002/1521-4141(200012)30:12 · Cited by 179 · see citing works
Bortoleti, B. T. D. S., Tomiotto‐Pellissier, F., Gonçalves, M. D., Miranda-Sapla, M. M., Assolini, J. P., Carloto, A. C. M., de Lima, D. M., Silveira, G. F., Almeida, R. S., Costa, I. N., et al. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.12.035 · Cited by 34 · see citing works
Ebrahimisadr, P., Ghaffarifar, F., & Hassan, Z. M. (2013) · Europe PMC (PubMed Central) · Cited by 33 · see citing works
Leishmania and its quest for iron: An update and overview
Zaidi, A., Singh, K. P., & Ali, V. (2016) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2016.12.004 · Cited by 34 · see citing works
Kocyigit, A., Gur, S., Erel, O., & Gurel, M. S. (2002) · Biological Trace Element Research · doi:10.1385/bter:90:1-3:47 · Cited by 30 · see citing works
Bortoleti, B. T. D. S., Gonçalves, M. D., Tomiotto‐Pellissier, F., Miranda-Sapla, M. M., Assolini, J. P., Carloto, A. C. M., Camargo, P. G., Cardoso, I. L. A., Simão, A. N. C., Arakawa, N. S., et al. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.06.010 · Cited by 28 · see citing works
Ortíz-Estrada, G., Luna‐Castro, S., Piña‐Vázquez, C., Samaniego-Barrón, L., León-Sicairos, N. M., Serrano‐Luna, J., & de la Garza, M. (2011) · Future Microbiology · doi:10.2217/fmb.11.140 · Cited by 27 · see citing works
“This finding agrees with results in other pathogens that require higher iron concentrations from these complexes than from host proteins (holoLf and Hb) [76,77].”
Resultde Figueiredo, R. C. B. Q., Rosa, D. S., Gomes, Y. M., Nakasawa, M., & Soares, M. J. (2004) · Parasitology · doi:10.1017/s0031182004005797 · Cited by 27 · see citing works
“It is also known that transferrin binding is limited to the flagellar pocket in T. brucei bloodstream forms (Steverding, 2000) and in Leishmania promastigotes (Wilson et al. 2002; Britigan et al. 1998; Wilson et al. 1994).”
BackgroundIron status and C‐reactive protein in canine leishmaniasis
Silvestrini, P., Zoia, A., Planellas, M., Roura, X., Pastor, J., Cerón, J. M. C., & Caldín, M. (2013) · Journal of Small Animal Practice · doi:10.1111/jsap.12172 · Cited by 26 · see citing works
“Uptake of iron from transferrin or lactoferrin by promastigotes appears to be critical in the first hours after infection of a mammalian host (Wilson et al. 1994).”
BackgroundPathological roles of macrophages in Leishmania infections
Goto, Y., & Mizobuchi, H. (2023) · Parasitology International · doi:10.1016/j.parint.2023.102738 · Cited by 25 · see citing works
Morimoto, A., Uchida, K., CHAMBERS, J. K., Sato, K., Hong, J., Sanjoba, C., Matsumoto, Y., Yamagishi, J., & Goto, Y. (2019) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007816 · Cited by 24 · see citing works
“Iron is also indispensable for the efficient survival of both intracellular and extracellular forms of Leishmania species [30,31].”
BackgroundAlkyl gallium(III) quinolinolates: A new class of highly selective anti-leishmanial agents
Duffin, R. N., Blair, V. L., Kedzierski, Ł., & Andrews, P. C. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111895 · Cited by 24 · see citing works
Pediatric visceral leishmaniasis in Albania
Kuli-Lito, G., Davachi, F., Sulcebe, G., Bregu, H., & Basha, M. (2002) · International Journal of Infectious Diseases · doi:10.1016/s1201-9712(02)90139-6 · Cited by 23 · see citing works
Quintal, S., Morais, T. S., Matos, C. P., Robalo, M. P., Piedade, M. F. M., de Brito, M. J. V., García, M. H., Marques, M., Maia, C., Campino, L., et al. (2013) · Journal of Organometallic Chemistry · doi:10.1016/j.jorganchem.2013.07.044 · Cited by 23 · see citing works
Entamoeba histolytica: Transferrin Binding Proteins
Reyes‐López, M., Serrano‐Luna, J., Negrete‐Abascal, E., León-Sicairos, N. M., Guerrero-Barrera, A. L., & de la Garza, M. (2001) · Experimental Parasitology · doi:10.1006/expr.2001.4647 · Cited by 23 · see citing works
The Availability of Iron Is Involved in the Murine Experimental Toxoplasma gondii Infection Outcome
Oliveira, M., Coutinho, L. B., Almeida, M. P. O., Briceño, M. P. P., Araújo, E. C. B., & Silva, N. M. (2020) · Microorganisms · doi:10.3390/microorganisms8040560 · Cited by 20 · see citing works
“chagasi have also developed mechanisms to utilize host transferrin and lactoferrin for growth [17].”
BackgroundHemoglobin Endocytosis and Intracellular Trafficking: A Novel Way of Heme Acquisition by Leishmania
Ansari, I., Basak, R., & Mukhopadhyay, A. (2022) · Pathogens · doi:10.3390/pathogens11050585 · Cited by 22 · see citing works
“Moreover, the parasite is efficiently grown in vitro in iron-depleted serum containing minimal essential medium supplemented with lactoferrin, indicating the acquisition of iron by Leishmania from lactoferrin [71].”
BackgroundSubramanya, S., & Mensa‐Wilmot, K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008538 · Cited by 21 · see citing works
Anand, N. (2024) · Frontiers in Parasitology · doi:10.3389/fpara.2023.1330398 · Cited by 20 · see citing works
Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis
Dighal, A., Mukhopadhyay, D., Sengupta, R., Moulik, S., Mukherjee, S., Roy, S., Chaudhuri, S. J., Das, N. K., & Chatterjee, M. (2020) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007991 · Cited by 19 · see citing works
“An important evolutionary adaptation in parasites is their acquisition of essential nutrients from host cells [4], which includes iron, a trace element essential for virtually all forms of life, as it functions as a cofactor of metabolic enzymes, oxygen transport and participates in immune surveillance [5].”
BackgroundMesquita‐Rodrigues, C., Menna‐Barreto, R. F. S., Vahia, L. S., Da-Silva, S. A. G., de Souza, E. M., Waghabi, M. C., Cuervo, P., & de Jesus, J. B. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002481 · Cited by 19 · see citing works
“Promastigote forms of Leishmania can acquire iron from transferrin [8], lactoferrin [9] and hemoglobin [10,11].”
BackgroundSen, S., Bal, S. K., Yadav, S., Mishra, P., Vishnu Vivek, G., Rastogi, R., & Mukhopadhyay, C. K. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102646 · Cited by 17 · see citing works
“(20) like acting as a cofactor in antioxidant enzyme superoxide dismutase (Fe-SOD) (21,22).”
BackgroundIron-Binding Protein Degradation by Cysteine Proteases ofNaegleria fowleri
Martínez‐Castillo, M., Rico, G. R., Serrano‐Luna, J., & Shibayama, M. (2015) · BioMed Research International · doi:10.1155/2015/416712 · Cited by 17 · see citing works
“Another mechanism involved in the acquisition of iron from lactoferrin has been reported in promastigotes of Leishmania chagasi, which use a surface reductase that recognizes and reduces ferric iron to the accessible ferrous form (Fe) [19].”
BackgroundIron-Modulated Virulence Factors of Entamoeba Histolytica
Gastelum-Martínez, A. A., León-Sicairos, C., Plata-Guzmán, L. Y., Soto-Castro, L., León-Sicairos, N. M., & de la Garza, M. (2018) · Future Microbiology · doi:10.2217/fmb-2018-0066 · Cited by 15 · see citing works
Britigan, B. E., Lewis, T. S., McCormick, M. L., & Wilson, M. E. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4757-9068-9_16 · Cited by 15 · see citing works
Self-citationAccess and utilization of host-derived iron by Leishmania parasites
Goto, Y., Ito, T., Ghosh, S., & Mukherjee, B. (2023) · The Journal of Biochemistry · doi:10.1093/jb/mvad082 · Cited by 14 · see citing works
“Although Leishmania are known to possess receptors for both transferrin and hemoglobin (12, 62) , holo-transferrin or hemoglobin may not to be the major forms of iron supply to intracellular amastigotes within the phagolysosomes.”
BackgroundActivity of Apo-Lactoferrin on Pathogenic Protozoa
Reyes‐López, M., Rico, G. R., Serrano‐Luna, J., & de la Garza, M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081702 · Cited by 14 · see citing works
“Promastigotes can rapidly take up 59Fe chelated by Lf, and this was inhibited by a 10-fold excess of unlabeled holo-Lf or apo-Lf [72].”
BackgroundWelter, B. H., Powell, R. R., Laughlin, R. C., McGugan, G. C., Bonner, M., King, A. V., & Temesvari, L. A. (2006) · Experimental Parasitology · doi:10.1016/j.exppara.2005.12.012 · Cited by 14 · see citing works
Adamama‐Moraitou, K. K., Saridomichelakis, M. N., Polizopoulou, Z. S., Kritsepi, M., Tsompanakou, A., & Koutinas, A. F. (2005) · Europe PMC (PubMed Central) · Cited by 14 · see citing works
Weinberg, G. A., Boelaert, J. R., & Weinberg, E. D. (2001) · Modern nutrition · doi:10.1201/9781420042351.ch7 · Cited by 13 · see citing works
Batista, L. F. S., Torrecilha, R. B. P., da Silva, R. B., Utsunomiya, Y. T., Silva, T. B. F., Tomokane, T. Y., Pacheco, A. D., Bosco, A. M., Paulan, S. D. C., Rossi, C. N., et al. (2020) · Veterinary Parasitology · doi:10.1016/j.vetpar.2020.109276 · Cited by 12 · see citing works
Ballesteros, C., Geary, J. F., Mackenzie, C. D., & Geary, T. G. (2018) · International Journal for Parasitology Drugs and Drug Resistance · doi:10.1016/j.ijpddr.2018.06.003 · Cited by 12 · see citing works
“Because iron is so important yet so tightly regulated and unavailable, pathogens have evolved sophisticated ways of acquiring iron from the host, including the expression of receptors that can bind iron transport proteins such as transferrin, lactoferrin or hemoglobin, or by the use of low molecular weight iron chelat…”
BackgroundForm, Function and Phylogenetic Relationships of Mosquito Immune Peptides
Lowenberger, C. A. (2001) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-1291-2_11 · Cited by 7 · see citing works
Naidu, A. S. (2000) · CRC Press eBooks · doi:10.1201/9781420039368.ch2 · Cited by 6 · see citing works
Datta, G., & Bera, T. (2001) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(01)00306-6 · Cited by 6 · see citing works
Transferrin Binding Proteins as a Means to Obtain Iron in Parasitic Protozoa
Reyes‐López, M., Serrano‐Luna, J., Pia-Vzquez, C., & de la Garz, M. (2012) · InTech eBooks · doi:10.5772/48288 · Cited by 5 · see citing works
“Lactoferrin, as an extracellular protein, interacts with promastigotes, and it can be used by them as an iron source in vitro [Wilson et al., 1994].”
BackgroundResultZhu, J., Bauzá‐Martinez, J., Gouw, J. W., Zhao, X., Heck, A. J. R., Stahl, B., Reiding, K. R., & Dingess, K. A. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1697081 · Cited by 1 · see citing works
POLSKIE TOWARZYSTWO MIKROBIOLOG"W POLISH SOCIETY OF MICROBIOLOGIS TS
Polonica, A. M. (2007) · Cited by 1 · see citing works
Specific Binding of Ferrilactoferrin and Ferritransferrin in the Protozoan Leishmania chagasi
McCormick, M. L., Wilson, M. E., Lewis, T. S., Vorhies, R. W., & Britigan, B. E. (1997) · Humana Press eBooks · doi:10.1007/978-1-4612-3956-7_21 · Cited by 1 · see citing works
Self-citationArmstrong, A. A., Sampaio, M. F. L. V., Galletto, G. C., & Faucz, F. R. (2005) · Estudos de Biologia · doi:10.7213/reb.v27i61.21934
Papel do ferro na infecção experimental por Toxoplasma gondii
Oliveira, M. (2018) · doi:10.14393/ufu.te.2018.61
Baroogh, Y. G., Khanaliha, K., Maleki, F., Torkashvand, H., & Tabatabaie, F. (2019) · Jundishapur Journal of Microbiology · doi:10.5812/jjm.95865
“These behaviors could justify the capability of the parasite in using iron from multiple sources in different host environments (17-19).”
BackgroundIron and Cell Proliferation: Mechanisms and Applications in Cancer Therapy
Testa, U. (2001) · CRC Press eBooks · doi:10.1201/b14262-5
(2000) · CRC Press eBooks · doi:10.1201/9781420041439.ch1
(2000) · CRC Press eBooks · doi:10.1201/9781420041439.fmatt
Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections
Chen, F., Wu, S., Chen, C., & Zhou, C. (2024) · World Journal of Hepatology · doi:10.4254/wjh.v16.i2.177
- Authors
- Wilson, M. E., Vorhies, R. W., Andersen, K. A., & Britigan, B. E.
- Affiliations
- University of Iowa (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1994-08
- Volume
- 62
- Issue
- 8
- Pages
- 3262-3269
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC302954
- OpenAlex
- W1916662323
- Cited by
- 79
- References
- 47
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 2 · 2013: 6 · 2012: 1
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29hl044275-05, 5r29ai030126-05)
- National Heart, Lung, and Blood Institute (R29 HL44275)
- National Institute of Allergy and Infectious Diseases (R29 AI30126, R01AI32135, R01AI032135)
- 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 infantum, iron acquisition, transferrin, lactoferrin, promastigotes, hemin, iron absorption, iron chelation, siderophores, hydrogen peroxide, hydroxyl radicals, visceral leishmaniasis
- MeSH terms
- Animals, Culture Media, Humans, Iron, Lactoferrin, Transferrin, Siderophores, Hydroxyl Radical, Leishmania infantum
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