The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Aghabi, Dana; Sloan, Megan; Gill, Grace; Hartmann, Elena; Antipova, Olga; Dou, Zhicheng; Guerra, Alfredo J.; Carruthers, Vern B.; Harding, Clare R.

doi:10.1038/s41467-023-39436-y

The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Journal Article · Tue Jun 20 00:00:00 EDT 2023 · Nature Communications

DOI:https://doi.org/10.1038/s41467-023-39436-y· OSTI ID:2470078

Aghabi, Dana ^[1]; ^[1]; ^[1]; Hartmann, Elena ^[1]; Antipova, Olga ^[2]; ^[3]; Guerra, Alfredo J. ^[4]; ^[5]; ^[1]

Univ. of Glasgow, Scotland (United Kingdom)
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Clemson Univ., SC (United States)
Univ. of Michigan, Ann Arbor, MI (United States); Cayman Chemical Company, Ann Arbor, MI (United States)
Univ. of Michigan, Ann Arbor, MI (United States)

Iron is essential to cells as a cofactor in enzymes of respiration and replication, however without correct storage, iron leads to the formation of dangerous oxygen radicals. In yeast and plants, iron is transported into a membrane-bound vacuole by the vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii. Here, we assess the role of VIT and iron storage in T. gondii. By deleting VIT, we find a slight growth defect in vitro, and iron hypersensitivity, confirming its essential role in parasite iron detoxification, which can be rescued by scavenging of oxygen radicals. We show VIT expression is regulated by iron at transcript and protein levels, and by altering VIT localization. In the absence of VIT, T. gondii responds by altering expression of iron metabolism genes and by increasing antioxidant protein catalase activity. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470078

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (98)

Ferritin, cellular iron storage and regulation: FERRITIN AND IRON STORAGE Arosio, Paolo; Elia, Leonardo; Poli, Maura IUBMB Life, Vol. 69, Issue 6 https://doi.org/10.1002/iub.1621	journal	March 2017
Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly Garland, Stacey A.; Hoff, Kevin; Vickery, Larry E. Journal of Molecular Biology, Vol. 294, Issue 4 https://doi.org/10.1006/jmbi.1999.3294	journal	December 1999
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method Livak, Kenneth J.; Schmittgen, Thomas D. Methods, Vol. 25, Issue 4 https://doi.org/10.1006/meth.2001.1262	journal	December 2001
Oxidative Stress as a Mechanism of Chronic Cadmium-Induced Hepatotoxicity and Renal Toxicity and Protection by Antioxidants Shaikh, Zahir A.; Vu, Thanhtam T.; Zaman, Khalequz Toxicology and Applied Pharmacology, Vol. 154, Issue 3 https://doi.org/10.1006/taap.1998.8586	journal	February 1999
Superoxide dismutase and catalase in Toxoplasma gondii David Sibley, L.; Lawson, Robin; Weidner, Earl Molecular and Biochemical Parasitology, Vol. 19, Issue 1 https://doi.org/10.1016/0166-6851(86)90069-1	journal	April 1986
Molecular cloning, expression analysis and iron metal cofactor characterisation of a superoxide dismutase from Toxoplasma gondii Ödberg-Ferragut, Carmen; Philippe Renault, Jean; Viscogliosi, Eric Molecular and Biochemical Parasitology, Vol. 106, Issue 1 https://doi.org/10.1016/S0166-6851(99)00211-X	journal	February 2000
Bacterial iron homeostasis Andrews, Simon C.; Robinson, Andrea K.; Rodríguez-Quiñones, Francisco FEMS Microbiology Reviews, Vol. 27, Issue 2-3 https://doi.org/10.1016/S0168-6445(03)00055-X	journal	June 2003
Metabolic remodeling in iron-deficient fungi Philpott, Caroline C.; Leidgens, Sébastien; Frey, Avery G. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1823, Issue 9 https://doi.org/10.1016/j.bbamcr.2012.01.012	journal	September 2012
Iron homeostasis and oxidative stress: An intimate relationship Galaris, Dimitrios; Barbouti, Alexandra; Pantopoulos, Kostas Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1866, Issue 12 https://doi.org/10.1016/j.bbamcr.2019.118535	journal	December 2019
Multiple roles of cadmium in cell death and survival Templeton, Douglas M.; Liu, Ying Chemico-Biological Interactions, Vol. 188, Issue 2 https://doi.org/10.1016/j.cbi.2010.03.040	journal	November 2010
A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes Sidik, Saima M.; Huet, Diego; Ganesan, Suresh M. Cell, Vol. 166, Issue 6 https://doi.org/10.1016/j.cell.2016.08.019	journal	September 2016
Identification of a Master Regulator of Differentiation in Toxoplasma Waldman, Benjamin S.; Schwarz, Dominic; Wadsworth, Marc H. Cell, Vol. 180, Issue 2 https://doi.org/10.1016/j.cell.2019.12.013	journal	January 2020
The Toxoplasma Vacuolar H+-ATPase Regulates Intracellular pH and Impacts the Maturation of Essential Secretory Proteins Stasic, Andrew J.; Chasen, Nathan M.; Dykes, Eric J. Cell Reports, Vol. 27, Issue 7 https://doi.org/10.1016/j.celrep.2019.04.038	journal	May 2019
Fluxes in “Free” and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum Marvin, Rebecca G.; Wolford, Janet L.; Kidd, Matthew J. Chemistry & Biology, Vol. 19, Issue 6 https://doi.org/10.1016/j.chembiol.2012.04.013	journal	June 2012
Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis Tong, Wing-Hang; Rouault, Tracey A. Cell Metabolism, Vol. 3, Issue 3 https://doi.org/10.1016/j.cmet.2006.02.003	journal	March 2006
Structure and function of the vacuolar Ccc1/VIT1 family of iron transporters and its regulation in fungi Sorribes-Dauden, Raquel; Peris, David; Martínez-Pastor, María Teresa Computational and Structural Biotechnology Journal, Vol. 18 https://doi.org/10.1016/j.csbj.2020.10.044	journal	January 2020
Toxoplasma gondii infection and toxoplasmosis in farm animals: Risk factors and economic impact Stelzer, S.; Basso, W.; Benavides Silván, J. Food and Waterborne Parasitology, Vol. 15 https://doi.org/10.1016/j.fawpar.2019.e00037	journal	June 2019
Iron sparing and recycling in a compartmentalized cell Blaby-Haas, Crysten E.; Merchant, Sabeeha S. Current Opinion in Microbiology, Vol. 16, Issue 6 https://doi.org/10.1016/j.mib.2013.07.019	journal	December 2013
Regulation of Ribonucleotide Reductase in Response to Iron Deficiency Sanvisens, Nerea; Bañó, M. Carmen; Huang, Mingxia Molecular Cell, Vol. 44, Issue 5 https://doi.org/10.1016/j.molcel.2011.09.021	journal	December 2011
Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability Unlu, Gokhan; Prizer, Benjamin; Erdal, Ranya Molecular Cell, Vol. 82, Issue 15 https://doi.org/10.1016/j.molcel.2022.05.024	journal	August 2022
The ABCs of multidrug resistance in malaria Koenderink, Jan B.; Kavishe, Reginald A.; Rijpma, Sanna R. Trends in Parasitology, Vol. 26, Issue 9 https://doi.org/10.1016/j.pt.2010.05.002	journal	September 2010
Catalase activity is stimulated by H2O2 in rich culture medium and is required for H2O2 resistance and adaptation in yeast Martins, Dorival; English, Ann M. Redox Biology, Vol. 2 https://doi.org/10.1016/j.redox.2013.12.019	journal	January 2014
Identifying the Target of an Antiparasitic Compound in Toxoplasma Using Thermal Proteome Profiling Herneisen, Alice L.; Sidik, Saima M.; Markus, Benedikt M. ACS Chemical Biology, Vol. 15, Issue 7 https://doi.org/10.1021/acschembio.0c00369	journal	June 2020
Detection of Chemical Engagement of Solute Carrier Proteins by a Cellular Thermal Shift Assay Hashimoto, Mari; Girardi, Enrico; Eichner, Ruth ACS Chemical Biology, Vol. 13, Issue 6 https://doi.org/10.1021/acschembio.8b00270	journal	May 2018
Genome-Wide Profiling of Responses to Cadmium in the Diatom Phaeodactylum tricornutum Brembu, Tore; Jørstad, Margrethe; Winge, Per Environmental Science & Technology, Vol. 45, Issue 18 https://doi.org/10.1021/es2002259	journal	August 2011
A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium Slavic, Ksenija; Krishna, Sanjeev; Lahree, Aparajita Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10403	journal	January 2016
HISAT: a fast spliced aligner with low memory requirements Kim, Daehwan; Langmead, Ben; Salzberg, Steven L. Nature Methods, Vol. 12, Issue 4 https://doi.org/10.1038/nmeth.3317	journal	March 2015
Rapid control of protein level in the apicomplexan Toxoplasma gondii Herm-Götz, Angelika; Agop-Nersesian, Carolina; Münter, Sylvia Nature Methods, Vol. 4, Issue 12 https://doi.org/10.1038/nmeth1134	journal	November 2007
High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method Gietz, R. Daniel; Schiestl, Robert H. Nature Protocols, Vol. 2, Issue 1 https://doi.org/10.1038/nprot.2007.13	journal	January 2007
Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages Wang, Yifan; Sangaré, Lamba Omar; Paredes-Santos, Tatiana C. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-18991-8	journal	October 2020
Crystal structure of plant vacuolar iron transporter VIT1 Kato, Takafumi; Kumazaki, Kaoru; Wada, Miki Nature Plants, Vol. 5, Issue 3 https://doi.org/10.1038/s41477-019-0367-2	journal	February 2019
Genome-wide SWAp-Tag yeast libraries for proteome exploration Weill, Uri; Yofe, Ido; Sass, Ehud Nature Methods, Vol. 15, Issue 8 https://doi.org/10.1038/s41592-018-0044-9	journal	July 2018
Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography Kapishnikov, Sergey; Grolimund, Daniel; Schneider, Gerd Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-06650-w	journal	August 2017
H-Ferritin is essential for macrophages’ capacity to store or detoxify exogenously added iron Mesquita, Gonçalo; Silva, Tânia; Gomes, Ana C. Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-59898-0	journal	February 2020
Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function Charvat, Robert A.; Arrizabalaga, Gustavo Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep22997	journal	March 2016
Recombinant vacuolar iron transporter family homologue PfVIT from human malaria-causing Plasmodium falciparum is a Fe2+/H+exchanger Labarbuta, Paola; Duckett, Katie; Botting, Catherine H. Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep42850	journal	February 2017
Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry Al-sandaqchi, Alaa T.; Brignell, Chris; Collingwood, Joanna F. Metallomics, Vol. 10, Issue 10 https://doi.org/10.1039/C8MT00136G	journal	January 2018
Regulation of cellular iron metabolism Wang, Jian; Pantopoulos, Kostas Biochemical Journal, Vol. 434, Issue 3 https://doi.org/10.1042/BJ20101825	journal	February 2011
The importance of eukaryotic ferritins in iron handling and cytoprotection Arosio, Paolo; Carmona, Fernando; Gozzelino, Raffaella Biochemical Journal, Vol. 472, Issue 1 https://doi.org/10.1042/BJ20150787	journal	October 2015
Interferon‐γ‐activated primary enterocytes inhibit Toxoplasma gondii replication: a role for intracellular iron No authors listed Immunology, Vol. 94, Issue 4 https://doi.org/10.1046/j.1365-2567.1998.00553.x	journal	August 1998
The antioxidant systems in Toxoplasma gondii and the role of cytosolic catalase in defence against oxidative injury Kwok, Lai Yu; Schlüter, Dirk; Clayton, Christine Molecular Microbiology, Vol. 51, Issue 1 https://doi.org/10.1046/j.1365-2958.2003.03823.x	journal	November 2003
CCC1 Is a Transporter That Mediates Vacuolar Iron Storage in Yeast Li, Liangtao; Chen, Opal S.; Ward, Diane McVey Journal of Biological Chemistry, Vol. 276, Issue 31 https://doi.org/10.1074/jbc.M103944200	journal	June 2001
Genetic Dissection of a Mitochondria-Vacuole Signaling Pathway in Yeast Reveals a Link between Chronic Oxidative Stress and Vacuolar Iron Transport Li, Liangtao; Murdock, Grace; Bagley, Dustin Journal of Biological Chemistry, Vol. 285, Issue 14 https://doi.org/10.1074/jbc.M109.096859	journal	April 2010
Genetic and Biochemical Analysis of High Iron Toxicity in Yeast Lin, Huilan; Li, Liangtao; Jia, Xuan Journal of Biological Chemistry, Vol. 286, Issue 5 https://doi.org/10.1074/jbc.M110.190959	journal	February 2011
The Import of Proteins into the Mitochondrion of Toxoplasma gondii van Dooren, Giel G.; Yeoh, Lee M.; Striepen, Boris Journal of Biological Chemistry, Vol. 291, Issue 37 https://doi.org/10.1074/jbc.M116.725069	journal	September 2016
Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion–transporting polypeptides Lee, Wooin; Ha, Jeong-min; Sugiyama, Yuichi Journal of Biological Chemistry, Vol. 295, Issue 50 https://doi.org/10.1074/jbc.REV120.009132	journal	December 2020
Trimmomatic: a flexible trimmer for Illumina sequence data Bolger, Anthony M.; Lohse, Marc; Usadel, Bjoern Bioinformatics, Vol. 30, Issue 15 https://doi.org/10.1093/bioinformatics/btu170	journal	April 2014
A plasma membrane-type Ca2+-ATPase co-localizes with a vacuolar H+-pyrophosphatase to acidocalcisomes of Toxoplasma gondii Luo, S. The EMBO Journal, Vol. 20, Issue 1 https://doi.org/10.1093/emboj/20.1.55	journal	January 2001
Transcriptional integration of plant responses to iron availability Gao, Fei; Dubos, Christian Journal of Experimental Botany, Vol. 72, Issue 6 https://doi.org/10.1093/jxb/eraa556	journal	November 2020
SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building Gouy, M.; Guindon, S.; Gascuel, O. Molecular Biology and Evolution, Vol. 27, Issue 2 https://doi.org/10.1093/molbev/msp259	journal	October 2009
Transporters Contributing to Iron Trafficking in Plants Conte, Sarah S.; Walker, Elsbeth L. Molecular Plant, Vol. 4, Issue 3 https://doi.org/10.1093/mp/ssr015	journal	May 2011
The HHpred interactive server for protein homology detection and structure prediction Soding, J.; Biegert, A.; Lupas, A. N. Nucleic Acids Research, Vol. 33, Issue Web Server https://doi.org/10.1093/nar/gki408	journal	July 2005
Thioredoxin reductase fromToxoplasma gondii: an essential virulence effector with antioxidant function Xue, Junxin; Jiang, Wei; Chen, Yongjun The FASEB Journal, Vol. 31, Issue 10 https://doi.org/10.1096/fj.201700008R	journal	July 2017
Identification of Two Novel Endoplasmic Reticulum Body-Specific Integral Membrane Proteins Yamada, Kenji; Nagano, Atsushi J.; Nishina, Momoko Plant Physiology, Vol. 161, Issue 1 https://doi.org/10.1104/pp.112.207654	journal	November 2012
Supply and demand—heme synthesis, salvage and utilization by Apicomplexa Kloehn, Joachim; Harding, Clare R.; Soldati‐Favre, Dominique The FEBS Journal, Vol. 288, Issue 2 https://doi.org/10.1111/febs.15445	journal	June 2020
Characterization of a novel organelle in Toxoplasma gondii with similar composition and function to the plant vacuole: Toxoplasma gondii plant-like vacuole Miranda, Kildare; Pace, Douglas A.; Cintron, Roxana Molecular Microbiology, Vol. 76, Issue 6 https://doi.org/10.1111/j.1365-2958.2010.07165.x	journal	April 2010
Ferritins control interaction between iron homeostasis and oxidative stress in Arabidopsis Ravet, Karl; Touraine, Brigitte; Boucherez, Jossia The Plant Journal, Vol. 57, Issue 3 https://doi.org/10.1111/j.1365-313X.2008.03698.x	journal	February 2009
Vacuolar membrane transporters OsVIT1 and OsVIT2 modulate iron translocation between flag leaves and seeds in rice Zhang, Yu; Xu, Yong-Han; Yi, Hong-Yin The Plant Journal, Vol. 72, Issue 3 https://doi.org/10.1111/j.1365-313X.2012.05088.x	journal	August 2012
Agrobacterium tumefaciens membrane-bound ferritin plays a role in protection against hydrogen peroxide toxicity and is negatively regulated by the iron response regulator Ruangkiattikul, Nantaporn; Bhubhanil, Sakkarin; Chamsing, Jareeya FEMS Microbiology Letters, Vol. 329, Issue 1 https://doi.org/10.1111/j.1574-6968.2012.02509.x	journal	February 2012
The Toxoplasma plant‐like vacuolar compartment (PLVAC) Stasic, Andrew J.; Moreno, Silvia N. J.; Carruthers, Vern B. Journal of Eukaryotic Microbiology, Vol. 69, Issue 6 https://doi.org/10.1111/jeu.12951	journal	October 2022
A vacuolar‐H⁺‐pyrophosphatase (TgVP1) is required for microneme secretion, host cell invasion, and extracellular survival of Toxoplasma gondii Liu, Jing; Pace, Douglas; Dou, Zhicheng Molecular Microbiology, Vol. 93, Issue 4 https://doi.org/10.1111/mmi.12685	journal	July 2014
A key cytosolic iron–sulfur cluster synthesis protein localizes to the mitochondrion of Toxoplasma gondii Aw, Yi Tong Vincent; Seidi, Azadeh; Hayward, Jenni A. Molecular Microbiology, Vol. 115, Issue 5 https://doi.org/10.1111/mmi.14651	journal	December 2020
The Medicago truncatula Vacuolar iron Transporter‐Like proteins VTL4 and VTL8 deliver iron to symbiotic bacteria at different stages of the infection process Walton, Jennifer H.; Kontra‐Kováts, Gyöngyi; Green, Robert T. New Phytologist, Vol. 228, Issue 2 https://doi.org/10.1111/nph.16735	journal	July 2020
Localization of Iron in Arabidopsis Seed Requires the Vacuolar Membrane Transporter VIT1 Kim, S. A.; Punshon, T.; Lanzirotti, A. Science, Vol. 314, Issue 5803 https://doi.org/10.1126/science.1132563	journal	November 2006
Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro Imlay, J.; Chin, S.; Linn, S. Science, Vol. 240, Issue 4852 https://doi.org/10.1126/science.2834821	journal	April 1988
Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound Portes, J. A.; Souza, T. G.; dos Santos, T. A. T. Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 12 https://doi.org/10.1128/AAC.00057-15	journal	December 2015
In Vitro Generation of Novel Pyrimethamine Resistance Mutations in theToxoplasma gondiiDihydrofolate Reductase Reynolds, Mary G.; Oh, Jung; Roos, David S. Antimicrobial Agents and Chemotherapy, Vol. 45, Issue 4 https://doi.org/10.1128/AAC.45.4.1271-1277.2001	journal	April 2001
Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations de Llanos, Rosa; Martínez-Garay, Carlos Andrés; Fita-Torró, Josep Applied and Environmental Microbiology, Vol. 82, Issue 10 https://doi.org/10.1128/AEM.00305-16	journal	May 2016
Yap5 Is an Iron-Responsive Transcriptional Activator That Regulates Vacuolar Iron Storage in Yeast Li, L.; Bagley, D.; Ward, D. M. Molecular and Cellular Biology, Vol. 28, Issue 4, p. 1326-1337 https://doi.org/10.1128/MCB.01219-07	journal	December 2007
A Toxoplasma Prolyl Hydroxylase Mediates Oxygen Stress Responses by Regulating Translation Elongation Florimond, Celia; Cordonnier, Charlotte; Taujale, Rahil mBio, Vol. 10, Issue 2 https://doi.org/10.1128/mBio.00234-19	journal	April 2019
Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins Dou, Zhicheng; McGovern, Olivia L.; Di Cristina, Manlio mBio, Vol. 5, Issue 4 https://doi.org/10.1128/mBio.01188-14	journal	July 2014
NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages Matta, Sumit K.; Patten, Kelley; Wang, Quiling mBio, Vol. 9, Issue 4 https://doi.org/10.1128/mBio.01393-18	journal	September 2018
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the Plasmodium falciparum STEVOR Protein Family Wichers, J. Stephan; Scholz, Judith A. M.; Strauss, Jan mBio, Vol. 10, Issue 4 https://doi.org/10.1128/mBio.01500-19	journal	August 2019
TgIF2K-B Is an eIF2α Kinase in Toxoplasma gondii That Responds to Oxidative Stress and Optimizes Pathogenicity Augusto, Leonardo; Martynowicz, Jennifer; Amin, Parth H. mBio, Vol. 12, Issue 1 https://doi.org/10.1128/mBio.03160-20	journal	February 2021
The Vacuolar Zinc Transporter TgZnT Protects Toxoplasma gondii from Zinc Toxicity Chasen, Nathan M.; Stasic, Andrew J.; Asady, Beejan mSphere, Vol. 4, Issue 3 https://doi.org/10.1128/mSphere.00086-19	journal	June 2019
The Cellular Thermal Shift Assay: A Novel Biophysical Assay for In Situ Drug Target Engagement and Mechanistic Biomarker Studies Martinez Molina, Daniel; Nordlund, Pär Annual Review of Pharmacology and Toxicology, Vol. 56, Issue 1 https://doi.org/10.1146/annurev-pharmtox-010715-103715	journal	January 2016
Effects of Iron Deprivation on Multidrug Resistance of Leukemic K562 Cells Fang, Dingzhu; Bao, Yixiao; Li, Xiaobin Chemotherapy, Vol. 56, Issue 1 https://doi.org/10.1159/000287352	journal	January 2010
H-Ferritin Subunit Overexpression in Erythroid Cells Reduces the Oxidative Stress Response and Induces Multidrug Resistance Properties Epsztejn, Silvina; Glickstein, Hava; Picard, Virginie Blood, Vol. 94, Issue 10 https://doi.org/10.1182/blood.V94.10.3593.422k26_3593_3603	journal	November 1999
Simple spectrophotometric assay for measuring catalase activity in biological tissues Hadwan, Mahmoud Hussein BMC Biochemistry, Vol. 19, Issue 1 https://doi.org/10.1186/s12858-018-0097-5	journal	August 2018
Characterization of the substrate binding site of an iron detoxifying membrane transporter from Plasmodium falciparum Sharma, Pragya; Tóth, Veronika; Hyland, Edel M. Malaria Journal, Vol. 20, Issue 1 https://doi.org/10.1186/s12936-021-03827-7	journal	June 2021
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Love, Michael I.; Huber, Wolfgang; Anders, Simon Genome Biology, Vol. 15, Issue 12 https://doi.org/10.1186/s13059-014-0550-8	journal	December 2014
Macrophage nutriprive antimicrobial mechanisms Appelberg, Rui Journal of Leukocyte Biology, Vol. 79, Issue 6 https://doi.org/10.1189/jlb.0206079	journal	April 2006
Vacuolar-Iron-Transporter1-Like Proteins Mediate Iron Homeostasis in Arabidopsis Gollhofer, Julia; Timofeev, Roman; Lan, Ping PLoS ONE, Vol. 9, Issue 10 https://doi.org/10.1371/journal.pone.0110468	journal	October 2014
Interferon-gamma promotes iron export in human macrophages to limit intracellular bacterial replication Abreu, Rodrigo; Essler, Lauren; Giri, Pramod PLOS ONE, Vol. 15, Issue 12 https://doi.org/10.1371/journal.pone.0240949	journal	December 2020
An ortholog of Plasmodium falciparum chloroquine resistance transporter (PfCRT) plays a key role in maintaining the integrity of the endolysosomal system in Toxoplasma gondii to facilitate host invasion Thornton, L. Brock; Teehan, Paige; Floyd, Katherine PLOS Pathogens, Vol. 15, Issue 6 https://doi.org/10.1371/journal.ppat.1007775	journal	June 2019
Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection Bergmann, Amy; Floyd, Katherine; Key, Melanie PLOS Pathogens, Vol. 16, Issue 5 https://doi.org/10.1371/journal.ppat.1008499	journal	May 2020
Novel aspects of iron homeostasis in pathogenic bloodstream form Trypanosoma brucei Gilabert Carbajo, Carla; Cornell, Lucy J.; Madbouly, Youssef PLOS Pathogens, Vol. 17, Issue 6 https://doi.org/10.1371/journal.ppat.1009696	journal	June 2021
Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii Rajendran, Esther; Clark, Morgan; Goulart, Cibelly PLOS Pathogens, Vol. 17, Issue 8 https://doi.org/10.1371/journal.ppat.1009816	journal	August 2021
Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma Pamukcu, Sarah; Cerutti, Aude; Bordat, Yann PLOS Pathogens, Vol. 17, Issue 11 https://doi.org/10.1371/journal.ppat.1010096	journal	November 2021
Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability Unlu, Gokhan Mendeley https://doi.org/10.17632/sg3b3f25p4.1	dataset	January 2022
Thermal Proteome Profiling to Identify Protein-ligand Interactions in the Apicomplexan Parasite Toxoplasma gondii Herneisen, Alice; Lourido, Sebastian BIO-PROTOCOL, Vol. 11, Issue 21 https://doi.org/10.21769/BioProtoc.4207	journal	January 2021
An Extracellular Redox Signal Triggers Calcium Release and Impacts the Asexual Development of Toxoplasma gondii Alves, Eduardo; Benns, Henry J.; Magnus, Lilian Frontiers in Cellular and Infection Microbiology, Vol. 11 https://doi.org/10.3389/fcimb.2021.728425	journal	August 2021
The Role of Reactive Oxygen Species in Arsenic Toxicity Hu, Yuxin; Li, Jin; Lou, Bin Biomolecules, Vol. 10, Issue 2 https://doi.org/10.3390/biom10020240	journal	February 2020
Preparing Adherent Cells for X-ray Fluorescence Imaging by Chemical Fixation Finney, Lydia A.; Jin, Qiaoling Journal of Visualized Experiments, Issue 97 https://doi.org/10.3791/52370	journal	March 2015
Mice with a Selective Impairment of IFN-γ Signaling in Macrophage Lineage Cells Demonstrate the Critical Role of IFN-γ–Activated Macrophages for the Control of Protozoan Parasitic Infections In Vivo Lykens, Jennifer E.; Terrell, Catherine E.; Zoller, Erin E. The Journal of Immunology, Vol. 184, Issue 2 https://doi.org/10.4049/jimmunol.0902346	journal	December 2009
Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. Adams, L. B.; Hibbs, J. B.; Taintor, R. R. The Journal of Immunology, Vol. 144, Issue 7 https://doi.org/10.4049/jimmunol.144.7.2725	journal	April 1990
Characterization of the substrate binding site of an iron detoxifying membrane transporter from Plasmodium falciparum Sharma, Pragya; Tóth, Veronika; Hyland, Edel M. figshare https://doi.org/10.6084/m9.figshare.c.5492299	collection	January 2021
Screening of candidate substrates and coupling ions of transporters by thermostability shift assays Majd, Homa; King, Martin S.; Palmer, Shane M. eLife, Vol. 7 https://doi.org/10.7554/eLife.38821	journal	October 2018

Similar Records

Structural and Functional Divergence of the Aldolase Fold in Toxoplasma gondii

Journal Article · Wed Oct 01 20:00:00 EDT 2014 · Journal of Molecular Biology · OSTI ID:1171854

A Toxoplasma gondii protein with homology to intracellular type Na{sup +}/H{sup +} exchangers is important for osmoregulation and invasion

Journal Article · Fri Jun 10 00:00:00 EDT 2011 · Experimental Cell Research · OSTI ID:22212143

Structure of Toxoplasma gondii fructose-1,6-bisphosphate aldolase

Journal Article · Fri Aug 29 00:00:00 EDT 2014 · Acta crystallographica. Section F, Structural biology communications · OSTI ID:22375702

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Iron
Parasite biology
Parasite physiology

The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Citation Formats

References (98)

Similar Records

Related Subjects