Therapeutic Targets on Toxoplasma gondii Parasite in Combatting Toxoplasmosis
Annual Research & Review in Biology,
Page 1-15
DOI:
10.9734/arrb/2019/v32i230081
Abstract
The status of toxoplasmosis management is challenged by drug intolerance, compromised efficacy and potential development of drug resistance. However, currently, there are very limited targets on T. gondii that serve as the site of action of current medications. This review aimed to explore more potential targets that are essential to parasite survival and are absent in humans. Many unexplored targets on T. gondii exist and their specificities to the parasite make them ideal drug targets. The present review had searched relevant English databases such as PubMed, Scopus, Google scholar and Science Direct, for relevant literature on the therapeutic target of T. gondii. Many of the enzyme systems in several pathways are essentially palatable as drug targets. Establishing compounds that can target these enzymes on T. gondii will greatly be beneficial in treating acute and chronic toxoplasmosis in humans.
Keywords:
- Toxoplasmosis
- T. gondii
- essential
- drug
- targets
- enzymes.
How to Cite
Abdullahi, S., Unyah, N., Nordin, N., Basir, R., Nasir, W., Alapid, A., Hassan, Y., Mustapha, T., & Majid, R. (2019). Therapeutic Targets on Toxoplasma gondii Parasite in Combatting Toxoplasmosis. Annual Research & Review in Biology, 32(2), 1-15. https://doi.org/10.9734/arrb/2019/v32i230081
References
Montazeri M, Sharif M, Sarvi S, Mehrzadi S, Ahmadpour E, Daryani A. A systematic review of in vitro and in vivo activities of anti-toxoplasma drugs and compounds (2006–2016). Frontiers in Microbiology. 2017;8.
Yan C, Liang LJ, Zheng KY, Zhu XQ. Impact of environmental factors on the emergence, transmission and distribution of Toxoplasma gondii. Parasites and vectors. 2016;9(1):137.
Doliwa C, Escotte-Binet S, Aubert D, Sauvage V, Velard F, Schmid A, Villena I. Sulfadiazine resistance in Toxoplasma gondii: No involvement of over expression or polymorphisms in genes of therapeutic targets and ABC transporters. Parasite. 2013;20:19.
Hunter CA, Sibley LD. Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nature Reviews Micro-biology. 2012;10(11):766.
Alday PH, Doggett JS. Drugs in develop-ment for toxoplasmosis: Advances, challenges, and current status. Drug Design, Development and Therapy. 2017; 11:273.
Gautam B, Singh G, Wadhwa G, Farmer R, Singh S, Singh AK, Yadav PK. Metabolic pathway analysis and molecular docking analysis for identification of putative drug targets in Toxoplasma gondii: novel approach. Bioinformation. 2012;8(3): 134-141.
Antczak M, Dzitko K, Długońska H. Human toxoplasmosis–Searching for novel chemotherapeutics. Biomedicine & Pharmacotherapy. 2016;82:677-684.
McAuley JB. Congenital toxoplasmosis. Journal of the Pediatric Infectious Diseases Society. 2014;3(Suppl_1):S30-S35.
Julliac B, Theophile H, Begorre M, Richez B, Haramburu F. Side effects of spiramycin masquerading as local anesthetic toxicity during labor epidural analgesia. Inter-national Journal of Obstetric Anesthesia. 2010;19(3):331-332.
Habib FA. Post-treatment assessment of acute Toxoplasma infection during pregnancy. Journal of Obstetrics and Gynaecology. 2008;28(6):593-595.
Paquet C, Yudin MH, Allen VM, Bouchard C, Boucher M, Caddy S, Van Schalkwyk J. Toxoplasmosis in pregnancy: Prevention, screening, and treatment. Journal of Obstetrics and Gynaecology Canada. 2013;35(1):78-79.
Bodaghi B, Touitou V, Fardeau C, Paris L, LeHoang P. Toxoplasmosis: New challenges for an old disease. Eye. 2012; 26(2):241.
Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965-1976.
Alves CF, Vitor RWA. Efficacy of atovaquone and sulfadiazine in the treat-ment of mice infected with Toxoplasma gondii strains isolated in Brazil. Parasite. 2005;12(2):171-177.
Sims PF. Drug resistance in Toxoplasma gondii. In Antimicrobial Drug Resistance Humana Press. 2009;1121-1126.
Aspinall TV, Joynson DH, Guy E, Hyde JE, Sims PF. The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis. Journal of Infectious Diseases. 2002;185(11):1637-1643.
Seeber F, Steinfelder S. Recent advances in understanding apicomplexan parasites. F1000Research. 2016;5.
McFadden DC, Camps M, Boothroyd JC. Resistance as a tool in the study of old and new drug targets in Toxoplasma. Drug Resistance Updates. 2001;4(2):79-84.
McFadden DC, Tomavo S, Berry EA, Boothroyd JC. Characterization of cytochrome b from Toxoplasma gondii and Qo domain mutations as a mechanism of atovaquone-resistance. Molecular and Biochemical Parasitology. 2000;108(1):1-12.
Meneceur P, Bouldouyre MA, Aubert D, Villena I, Menotti J, Sauvage V, Derouin F. In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrime-thamine, sulfadiazine, and atovaquone. Antimicrobial Agents and Chemotherapy. 2008;52(4):1269-1277.
Müller J, Hemphill A. New approaches for the identification of drug targets in proto-zoan parasites. In International Review of Cell and Molecular Biology. Academic Press. 2013;301:359-401.
Lim DC, Cooke BM, Doerig C, Saeij JP. Toxoplasma and Plasmodium protein kinases: Roles in invasion and host cell remodeling. International Journal for Parasitology. 2012;42(1):21-32.
Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: Functions and drug targets. Parasitology Research. 2013; 112(6):2121-2129.
Wang Y, Yin H. Research advances in microneme protein 3 of Toxoplasma gondii. Parasites & Vectors. 2015;8(1):384.
Peixoto L, Chen F, Harb OS, Davis PH, Beiting DP, Brownback CS, Roos DS. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host & Microbe. 2010;8(2):208-218.
Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, DeRocher AE, Inampudi KK, Napuli AJ. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nature Structural and Molecular Biology. 2010; 17(5):602.
Kato K, Sugi T, Iwanaga T. Roles of apicomplexan protein kinases at each life cycle stage. Parasitology International. 2012;61(2):224-234.
Morlon‐Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. The Toxoplasma gondii calcium‐dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cellular Microbiology. 2014;16(1):95-114.
Doggett JS, Ojo KK, Fan E, Maly DJ, Van Voorhis WC. Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection. Antimicrobial agents and Chemo-therapy. 2014;58(6):3547-3549.
Moine E, Dimier-Poisson I, Enguehard-Gueiffier C, Logé C, Pénichon M, Moiré N, Gueiffier A. Development of new highly potent imidazo [1, 2-b] pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1. European Journal of Medicinal Chemistry. 2015;105: 80-105.
Zhang Z, Ojo KK, Johnson SM, Larson ET, He P, Geiger JA, Maly DJ. Benzoylbenzi-midazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorganic & Medicinal Chemistry Letters. 2012;22(16):5264-5267.
Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature. 2010; 465(7296):359.
Chen K, Wang JL, Huang SY, Yang WB, Zhu WN, Zhu XQ. Immune responses and protection after DNA vaccination against Toxoplasma gondii calcium-dependent protein kinase 2 (TgCDPK2). Parasite. 2017;24:41.
Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ. Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly (lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infectious Diseases. 2016;16(1):168.
McCoy JM, Whitehead L, van Dooren GG, Tonkin CJ. TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells. PLoS Pathogens. 2012; 8(12):e1003066.
Garrison E, Treeck M, Ehret E, Butz H, Garbuz T, Oswald BP, Arrizabalaga G. A forward genetic screen reveals that calcium-dependent protein kinase 3 regulates egress in Toxoplasma. PLoS Pathogens. 2012;8(11):e1003049.
Dan-Goor M, Nasereddin A, Jaber H, Jaffe CL. Identification of a secreted casein kinase 1 in Leishmania donovani: Effect of protein over expression on parasite growth and virulence. PLoS One. 2013;8(11): e79287.
Allocco JJ, Donald R, Zhong T, Lee A, Tang YS, Hendrickson RC, Nare B. Inhibitors of casein kinase 1 block the growth of Leishmania major promastigotes in vitro. International Journal for Parasito-logy. 2006;36(12):1249-1259.
Donald RG, Zhong T, Meijer L, Liberator PA. Characterization of two T. gondii CK1 isoforms. Molecular and Biochemical Parasitology. 2005;141(1):15-27.
Wei S, Marches F, Daniel B, Sonda S, Heidenreich K, Curiel T. Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication. International Journal for Parasitology. 2002;32(8):969-977.
Brumlik MJ, Wei S, Finstad K, Nesbit J, Hyman LE, Lacey M, Curiel TJ. Identifi-cation of a novel mitogen-activated protein kinase in Toxoplasma gondii. International Journal for Parasitology. 2004;34(11): 1245-1254.
Brumlik MJ, Pandeswara S, Ludwig SM, Jeansonne DP, Lacey MR, Murthy K, Hurez V. TgMAPK1 is a Toxoplasma gondii MAP kinase that hijacks host MKK3 signals to regulate virulence and inter-feron-γ-mediated nitric oxide production. Experimental Parasitology. 2013;134(3): 389-399.
Huang H, Fen Y, Bao Y, Lee H, Lisanti MP, Tanowitz H, Weiss LM. Molecular cloning and characterization of mitogen-activated protein kinase 2 in Toxoplasma gondii. Cell Cycle. 2011;10(20):3519-3526.
Donald RG, Allocco J, Singh SB, Nare B, Salowe SP, Wiltsie J, Liberator PA. Toxoplasma gondii cyclic GMP-dependent kinase: Chemotherapeutic targeting of an essential parasite protein kinase. Eukaryotic Cell. 2002;1(3):317-328.
Gurnett AM, Liberator PA, Dulski PM, Salowe SP, Donald RG, Anderson JW, Darkin-Rattray SJ. Purification and mole-cular characterization of cGMP-dependent protein kinase from apicomplexan parasites a novel chemotherapeutic target. Journal of Biological Chemistry. 2002;277(18): 15913-15922.
Cardew EM, Verlinde CL, Pohl E. The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design. Parasitology. 2018; 145(2):210-218.
Kurokawa H, Kato K, Iwanaga T, Sugi T, Sudo A, Kobayashi K, Akashi H. Identifica-tion of Toxoplasma gondii cAMP dependent protein kinase and its role in the tachyzoite growth. PLoS One. 2011;6(7):e22492.
Sugi T, Ma YF, Tomita T, Murakoshi F, Eaton MS, Yakubu R, Gupta N. Toxoplasma gondii cyclic AMP-dependent protein kinase subunit 3 is involved in the switch from tachyzoite to bradyzoite development. MBio. 2016;7(3):e00755- 16.
Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D, Arenas AF, Saeij JP. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLoS Pathogens 2012; 8(6):e1002784.
Sibley LD. Development of forward genetics in Toxoplasma gondii. Inter-national Journal for Parasitology. 2009; 39(8):915-924.
El Hajj H, Demey E, Poncet J, Lebrun M, Wu B, Galéotti N, Dubremetz JF. The ROP2 family of Toxoplasma gondii rhoptry proteins: Proteomic and genomic charac-terization and molecular modeling. Proteomics. 2006;6(21):5773-5784.
Pernas L, Boothroyd JC. Association of host mitochondria with the parasitophorous vacuole during Toxoplasma infection is not dependent on rhoptry proteins ROP2/8. International Journal for Parasitology. 2010;40(12):1367-1371.
Behnke MS, Khan A, Wootton JC, Dubey JP, Tang K, Sibley LD. Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. Proceedings of the National Academy of Sciences. 2011; 108(23):9631-9636.
Blader IJ, Saeij JP. Communication between Toxoplasma gondii and its host: Impact on parasite growth, development, immune evasion and virulence. APMIS. 2010;117(5-6):458-476.
Felix Y. Innate immunity to Toxoplasma gondii infection. Nature Reviews Immuno-logy. 2014;14:109–121.
Zhang NZ, Huang SY, Zhou DH, Chen J, Xu Y, Tian WP, Zhu XQ. Protective immunity against Toxoplasma gondii induced by DNA immunization with the gene encoding a novel vaccine candidate: Calcium-dependent protein kinase 3. BMC Infectious Diseases. 2013;13(1):512.
Saremy S, Boroujeni ME, Bhattacharjee B, Mittal V, Chatterjee J. Identification of potential apicoplast associated therapeutic targets in human and animal pathogen Toxoplasma gondii ME49. Bioinformation. 2011;7(8):379-83.
Sonda S, Hehl AB. Lipid biology of Apicomplexa: Perspectives for new drug targets, particularly for Toxoplasma gondii. TRENDS in Parasitology. 2006;22(1):41-47.
Gornicki P. Apicoplast fatty acid biosyn-thesis as a target for medical intervention in apicomplexan parasites. International Journal for Parasitology. 2003;33(9):885-896.
Seeber F. Biosynthetic pathways of plastid-derived organelles as potential drug targets against parasitic apicomplexa. Current Drug Targets-Immune, Endocrine & Metabolic Disorders. 2003;3(2):99-109.
Seeber F, Soldati-Favre D. Metabolic pathways in the apicoplast of apicomplexa. International Review of Cell and Molecular Biology. 2010;281:161-228.
Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK. Inhibitors of the nonm-evalonate pathway of isoprenoid bio-synthesis as antimalarial drugs. Science. 1999;285:1573–1576.
Ling Y, Sahota G, Odeh S, Chan JM, Araujo FG, Moreno SN, Oldfield E. Bisphosphonate inhibitors of Toxoplasma gondii growth: In vitro, QSAR, and in vivo investigations. Journal of Medicinal Chemistry. 2005;48(9):3130-3140.
Clastre M, Goubard A, Prel A, Mincheva Z, Viaud-Massuart MC, Bout D, Laurent F. The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: Presence and sensitivity to fosmidomycin. Experimental Parasitology. 2007;116(4): 375-384.
McLeod R, Muench SP, Rafferty JB, Kyle DE, Mui EJ, Kirisits MJ, Dorris M. Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of Apicomplexan Fab I. International Journal for Parasitology. 2001;31(2):109-113.
Waller RF, Keeling PJ, Donald RG, Striepen B, Handman E, Lang-Unnasch N, McFadden GI. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proceedings of the National Academy of Sciences. 1998;95(21):12352-12357.
Zuther E, Johnson JJ, Haselkorn R, McLeod R, Gornicki P. Growth of Toxoplasma gondii is inhibited by aryloxy-phenoxypropionate herbicides targeting acetyl-CoA carboxylase. Proceedings of the National Academy of Sciences. 1999; 96(23):13387-13392.
Gozalbes R, Brun-Pascaud M, Garcia-Domenech R, Galvez J, Girard PM, Doucet JP, Derouin F. Anti-toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: Prediction of activity by molecular topology and virtual computational techniques. Antimicrobial Agents and Chemo-therapy. 2000;44(10):2771- 2776.
Divo AA, Sartorelli AC, Patton CL, Bia FJ. Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrobial Agents and Chemotherapy. 1988;32(8):1182-1186.
Woods KM, Nesterenko MV, Upton SJ. Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro. Annals of Tropical Medicine & Parasitology. 1996; 90(6):603-615.
García-Estrada C, Prada CF, Fernández-Rubio C, Rojo-Vázquez F, Balaña-Fouce R. DNA topoisomerases in apicomplexan parasites: Promising targets for drug discovery. Proceedings of the Royal Society of London B: Biological Sciences. 2010;277(1689):1777-1787.
Maxwell A. DNA gyrase as a drug target. Trends in Microbiology. 1997;5(3):102-109.
McFadden GI, Roos DS. Apicomplexan plastids as drug targets. Trends in Microbiology. 1999;7(8):328-333.
Khan AA, Slifer T, Araujo FG, Remington JS. Trovafloxacin is active against Toxoplasma gondii. Antimicrobial agents and Chemotherapy. 1996;40(8):1855-1859.
Ralph SA, D'Ombrain MC, McFadden GI. The apicoplast as an antimalarial drug target. Drug Resistance Updates. 2001; 4(3):145-151.
Reiff SB, Vaishnava S, Striepen B. The HU protein is important for apicoplast genome maintenance and inheritance in Toxoplasma gondii. Eukaryotic Cell. 2012; 11(7):905-915.
Lüder CG, Seeber F. Toxoplasma. In molecular parasitology. Springer, Vienna. 2016;217-239.
Pfefferkorn ER, Nothnagel RF, Borotz SE. Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrobial Agents and Chemotherapy. 1992;36(5):1091-1096.
Shanmugam D, Wu B, Ramirez U, Jaffe EK, Roos DS. Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii kinetic and structural properties validate therapeutic potential. Journal of Biological Chemistry. 2010; 285(29):22122-22131.
van Dooren GG, Kennedy AT, McFadden GI. The use and abuse of heme in apicomplexan parasites. Antioxidants & Redox Signaling. 2012;17(4):634-656.
Sun H, Zhuo X, Zhao X, Yang Y, Chen X, Yao C, Du A. The heat shock protein 90 of Toxoplasma gondii is essential for invasion of host cells and tachyzoite growth. Parasite. 2017;24.
Ashwinder K, Kho MT, Chee PM, Lim WZ, Yap IK, Choi SB, Yam WK. Targeting heat shock proteins 60 and 70 of Toxoplasma gondii as a potential drug target: In silico approach. Interdisciplinary Sciences: Computational Life Sciences. 2016;8(4): 374-387.
Toursel C, Dzierszinski F, Bernigaud A, Mortuaire M, Tomavo S. Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii. Molecular and Biochemical Parasitology. 2000;111(2): 319-332.
Dobbin CA, Smith NC, Johnson AM. Heat shock protein 70 is a potential virulence factor in murine Toxoplasma infection via immunomodulation of host NF-κB and nitric oxide. The Journal of Immunology. 2002;169(2):958-965.
Müller S, Liebau E, Walter RD, Krauth-Siegel RL. Thiol-based redox metabolism of protozoan parasites. Trends in Parasitology. 2003;19(7):320-328.
Weiss LM, Kim K. The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci. 2011;5:D391-D405.
Denton H, Robert CW, Alexander J, Thong KW, Coombs GH. Enzymes of energy metabolism in the bradyzoite and tachyzoites of Toxoplasma gondii. FEMS Microbio Lett. 1996;137:103-8.
Al-Anouti F, Tomavo S, Parmley S, Ananvoranich S. The expression of lactate dehydrogenase is important for the cell cycle of Toxoplasma gondii. Journal of Biological Chemistry. 2004;279(50):52300-52311.
Abdelbaset AE, Fox BA, Karram MH, Ellah MRA, Bzik DJ, Igarashi M. Lactate dehydrogenase in Toxoplasma gondii controls virulence, bradyzoite differentiation and chronic infection. PloS One. 2017; 12(3):e0173745.
Kim YA, Sharon A, Chu CK, Rais RH, Al Safarjalani ON, Naguib FN, el Kouni MH. Structure− activity relationships of 7-deaza-6-benzylthioinosine analogues as ligands of Toxoplasma gondii adenosine kinase. Journal of Medicinal Chemistry. 2008;51(13):3934-3945.
Blume M, Nitzsche R, Sternberg U, Gerlic M, Masters SL, Gupta N, McConville MJ. A Toxoplasma gondii gluconeogenic enzyme contributes to robust central carbon metabolism and is essential for replication and virulence. Cell Host & Microbe. 2015; 18(2):210-220.
Coppens I, Sinai AP, Joiner KA. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated en ocytosis for cholesterol acquisition. J Cell Bio. 2000;149:167-180.
Sanfelice RA, da Silva SS, Bosqui LR, Miranda-Sapla MM, Barbosa BF, Silva RJ, Conchon-Costa I. Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells. Acta Tropica. 2017; 167:208-215.
Gupta Nishith, Matthew M. Zahn, Isabelle Coppens, Keith A. Joiner, Dennis R. Voelker. Selective disruption of phos-phatidylcholine metabolism of the intracellular parasite Toxoplasma gondii arrests its growth. The Journal of Biological Chemistry. 2005;280(16): 16345–16353.
Ancelin ML, Vial HJ. Quartenary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport. Anti-microbial Agents and Chemotherapy. 1986;29(5):814-820.
Tipparaju SK, Muench SP, Mui EJ, Ruzheinikov SN, Lu JZ, Hutson SL, Kozikowski AP. Identification and develop-ment of novel inhibitors of Toxoplasma gondii enoyl reductase. Journal of Medicinal Chemistry. 2010;53(17):6287-6300.
Cheng G, Muench SP, Zhou Y, Afanador GA, Mui EJ, Fomovska A, Hickman MR. Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase. Bioorganic & Medicinal Chemistry Letters. 2013;23(7):2035-2043.
Yan C, Liang LJ, Zheng KY, Zhu XQ. Impact of environmental factors on the emergence, transmission and distribution of Toxoplasma gondii. Parasites and vectors. 2016;9(1):137.
Doliwa C, Escotte-Binet S, Aubert D, Sauvage V, Velard F, Schmid A, Villena I. Sulfadiazine resistance in Toxoplasma gondii: No involvement of over expression or polymorphisms in genes of therapeutic targets and ABC transporters. Parasite. 2013;20:19.
Hunter CA, Sibley LD. Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nature Reviews Micro-biology. 2012;10(11):766.
Alday PH, Doggett JS. Drugs in develop-ment for toxoplasmosis: Advances, challenges, and current status. Drug Design, Development and Therapy. 2017; 11:273.
Gautam B, Singh G, Wadhwa G, Farmer R, Singh S, Singh AK, Yadav PK. Metabolic pathway analysis and molecular docking analysis for identification of putative drug targets in Toxoplasma gondii: novel approach. Bioinformation. 2012;8(3): 134-141.
Antczak M, Dzitko K, Długońska H. Human toxoplasmosis–Searching for novel chemotherapeutics. Biomedicine & Pharmacotherapy. 2016;82:677-684.
McAuley JB. Congenital toxoplasmosis. Journal of the Pediatric Infectious Diseases Society. 2014;3(Suppl_1):S30-S35.
Julliac B, Theophile H, Begorre M, Richez B, Haramburu F. Side effects of spiramycin masquerading as local anesthetic toxicity during labor epidural analgesia. Inter-national Journal of Obstetric Anesthesia. 2010;19(3):331-332.
Habib FA. Post-treatment assessment of acute Toxoplasma infection during pregnancy. Journal of Obstetrics and Gynaecology. 2008;28(6):593-595.
Paquet C, Yudin MH, Allen VM, Bouchard C, Boucher M, Caddy S, Van Schalkwyk J. Toxoplasmosis in pregnancy: Prevention, screening, and treatment. Journal of Obstetrics and Gynaecology Canada. 2013;35(1):78-79.
Bodaghi B, Touitou V, Fardeau C, Paris L, LeHoang P. Toxoplasmosis: New challenges for an old disease. Eye. 2012; 26(2):241.
Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965-1976.
Alves CF, Vitor RWA. Efficacy of atovaquone and sulfadiazine in the treat-ment of mice infected with Toxoplasma gondii strains isolated in Brazil. Parasite. 2005;12(2):171-177.
Sims PF. Drug resistance in Toxoplasma gondii. In Antimicrobial Drug Resistance Humana Press. 2009;1121-1126.
Aspinall TV, Joynson DH, Guy E, Hyde JE, Sims PF. The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis. Journal of Infectious Diseases. 2002;185(11):1637-1643.
Seeber F, Steinfelder S. Recent advances in understanding apicomplexan parasites. F1000Research. 2016;5.
McFadden DC, Camps M, Boothroyd JC. Resistance as a tool in the study of old and new drug targets in Toxoplasma. Drug Resistance Updates. 2001;4(2):79-84.
McFadden DC, Tomavo S, Berry EA, Boothroyd JC. Characterization of cytochrome b from Toxoplasma gondii and Qo domain mutations as a mechanism of atovaquone-resistance. Molecular and Biochemical Parasitology. 2000;108(1):1-12.
Meneceur P, Bouldouyre MA, Aubert D, Villena I, Menotti J, Sauvage V, Derouin F. In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrime-thamine, sulfadiazine, and atovaquone. Antimicrobial Agents and Chemotherapy. 2008;52(4):1269-1277.
Müller J, Hemphill A. New approaches for the identification of drug targets in proto-zoan parasites. In International Review of Cell and Molecular Biology. Academic Press. 2013;301:359-401.
Lim DC, Cooke BM, Doerig C, Saeij JP. Toxoplasma and Plasmodium protein kinases: Roles in invasion and host cell remodeling. International Journal for Parasitology. 2012;42(1):21-32.
Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: Functions and drug targets. Parasitology Research. 2013; 112(6):2121-2129.
Wang Y, Yin H. Research advances in microneme protein 3 of Toxoplasma gondii. Parasites & Vectors. 2015;8(1):384.
Peixoto L, Chen F, Harb OS, Davis PH, Beiting DP, Brownback CS, Roos DS. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host & Microbe. 2010;8(2):208-218.
Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, DeRocher AE, Inampudi KK, Napuli AJ. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nature Structural and Molecular Biology. 2010; 17(5):602.
Kato K, Sugi T, Iwanaga T. Roles of apicomplexan protein kinases at each life cycle stage. Parasitology International. 2012;61(2):224-234.
Morlon‐Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. The Toxoplasma gondii calcium‐dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cellular Microbiology. 2014;16(1):95-114.
Doggett JS, Ojo KK, Fan E, Maly DJ, Van Voorhis WC. Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection. Antimicrobial agents and Chemo-therapy. 2014;58(6):3547-3549.
Moine E, Dimier-Poisson I, Enguehard-Gueiffier C, Logé C, Pénichon M, Moiré N, Gueiffier A. Development of new highly potent imidazo [1, 2-b] pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1. European Journal of Medicinal Chemistry. 2015;105: 80-105.
Zhang Z, Ojo KK, Johnson SM, Larson ET, He P, Geiger JA, Maly DJ. Benzoylbenzi-midazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorganic & Medicinal Chemistry Letters. 2012;22(16):5264-5267.
Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature. 2010; 465(7296):359.
Chen K, Wang JL, Huang SY, Yang WB, Zhu WN, Zhu XQ. Immune responses and protection after DNA vaccination against Toxoplasma gondii calcium-dependent protein kinase 2 (TgCDPK2). Parasite. 2017;24:41.
Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ. Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly (lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infectious Diseases. 2016;16(1):168.
McCoy JM, Whitehead L, van Dooren GG, Tonkin CJ. TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells. PLoS Pathogens. 2012; 8(12):e1003066.
Garrison E, Treeck M, Ehret E, Butz H, Garbuz T, Oswald BP, Arrizabalaga G. A forward genetic screen reveals that calcium-dependent protein kinase 3 regulates egress in Toxoplasma. PLoS Pathogens. 2012;8(11):e1003049.
Dan-Goor M, Nasereddin A, Jaber H, Jaffe CL. Identification of a secreted casein kinase 1 in Leishmania donovani: Effect of protein over expression on parasite growth and virulence. PLoS One. 2013;8(11): e79287.
Allocco JJ, Donald R, Zhong T, Lee A, Tang YS, Hendrickson RC, Nare B. Inhibitors of casein kinase 1 block the growth of Leishmania major promastigotes in vitro. International Journal for Parasito-logy. 2006;36(12):1249-1259.
Donald RG, Zhong T, Meijer L, Liberator PA. Characterization of two T. gondii CK1 isoforms. Molecular and Biochemical Parasitology. 2005;141(1):15-27.
Wei S, Marches F, Daniel B, Sonda S, Heidenreich K, Curiel T. Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication. International Journal for Parasitology. 2002;32(8):969-977.
Brumlik MJ, Wei S, Finstad K, Nesbit J, Hyman LE, Lacey M, Curiel TJ. Identifi-cation of a novel mitogen-activated protein kinase in Toxoplasma gondii. International Journal for Parasitology. 2004;34(11): 1245-1254.
Brumlik MJ, Pandeswara S, Ludwig SM, Jeansonne DP, Lacey MR, Murthy K, Hurez V. TgMAPK1 is a Toxoplasma gondii MAP kinase that hijacks host MKK3 signals to regulate virulence and inter-feron-γ-mediated nitric oxide production. Experimental Parasitology. 2013;134(3): 389-399.
Huang H, Fen Y, Bao Y, Lee H, Lisanti MP, Tanowitz H, Weiss LM. Molecular cloning and characterization of mitogen-activated protein kinase 2 in Toxoplasma gondii. Cell Cycle. 2011;10(20):3519-3526.
Donald RG, Allocco J, Singh SB, Nare B, Salowe SP, Wiltsie J, Liberator PA. Toxoplasma gondii cyclic GMP-dependent kinase: Chemotherapeutic targeting of an essential parasite protein kinase. Eukaryotic Cell. 2002;1(3):317-328.
Gurnett AM, Liberator PA, Dulski PM, Salowe SP, Donald RG, Anderson JW, Darkin-Rattray SJ. Purification and mole-cular characterization of cGMP-dependent protein kinase from apicomplexan parasites a novel chemotherapeutic target. Journal of Biological Chemistry. 2002;277(18): 15913-15922.
Cardew EM, Verlinde CL, Pohl E. The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design. Parasitology. 2018; 145(2):210-218.
Kurokawa H, Kato K, Iwanaga T, Sugi T, Sudo A, Kobayashi K, Akashi H. Identifica-tion of Toxoplasma gondii cAMP dependent protein kinase and its role in the tachyzoite growth. PLoS One. 2011;6(7):e22492.
Sugi T, Ma YF, Tomita T, Murakoshi F, Eaton MS, Yakubu R, Gupta N. Toxoplasma gondii cyclic AMP-dependent protein kinase subunit 3 is involved in the switch from tachyzoite to bradyzoite development. MBio. 2016;7(3):e00755- 16.
Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D, Arenas AF, Saeij JP. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLoS Pathogens 2012; 8(6):e1002784.
Sibley LD. Development of forward genetics in Toxoplasma gondii. Inter-national Journal for Parasitology. 2009; 39(8):915-924.
El Hajj H, Demey E, Poncet J, Lebrun M, Wu B, Galéotti N, Dubremetz JF. The ROP2 family of Toxoplasma gondii rhoptry proteins: Proteomic and genomic charac-terization and molecular modeling. Proteomics. 2006;6(21):5773-5784.
Pernas L, Boothroyd JC. Association of host mitochondria with the parasitophorous vacuole during Toxoplasma infection is not dependent on rhoptry proteins ROP2/8. International Journal for Parasitology. 2010;40(12):1367-1371.
Behnke MS, Khan A, Wootton JC, Dubey JP, Tang K, Sibley LD. Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. Proceedings of the National Academy of Sciences. 2011; 108(23):9631-9636.
Blader IJ, Saeij JP. Communication between Toxoplasma gondii and its host: Impact on parasite growth, development, immune evasion and virulence. APMIS. 2010;117(5-6):458-476.
Felix Y. Innate immunity to Toxoplasma gondii infection. Nature Reviews Immuno-logy. 2014;14:109–121.
Zhang NZ, Huang SY, Zhou DH, Chen J, Xu Y, Tian WP, Zhu XQ. Protective immunity against Toxoplasma gondii induced by DNA immunization with the gene encoding a novel vaccine candidate: Calcium-dependent protein kinase 3. BMC Infectious Diseases. 2013;13(1):512.
Saremy S, Boroujeni ME, Bhattacharjee B, Mittal V, Chatterjee J. Identification of potential apicoplast associated therapeutic targets in human and animal pathogen Toxoplasma gondii ME49. Bioinformation. 2011;7(8):379-83.
Sonda S, Hehl AB. Lipid biology of Apicomplexa: Perspectives for new drug targets, particularly for Toxoplasma gondii. TRENDS in Parasitology. 2006;22(1):41-47.
Gornicki P. Apicoplast fatty acid biosyn-thesis as a target for medical intervention in apicomplexan parasites. International Journal for Parasitology. 2003;33(9):885-896.
Seeber F. Biosynthetic pathways of plastid-derived organelles as potential drug targets against parasitic apicomplexa. Current Drug Targets-Immune, Endocrine & Metabolic Disorders. 2003;3(2):99-109.
Seeber F, Soldati-Favre D. Metabolic pathways in the apicoplast of apicomplexa. International Review of Cell and Molecular Biology. 2010;281:161-228.
Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK. Inhibitors of the nonm-evalonate pathway of isoprenoid bio-synthesis as antimalarial drugs. Science. 1999;285:1573–1576.
Ling Y, Sahota G, Odeh S, Chan JM, Araujo FG, Moreno SN, Oldfield E. Bisphosphonate inhibitors of Toxoplasma gondii growth: In vitro, QSAR, and in vivo investigations. Journal of Medicinal Chemistry. 2005;48(9):3130-3140.
Clastre M, Goubard A, Prel A, Mincheva Z, Viaud-Massuart MC, Bout D, Laurent F. The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: Presence and sensitivity to fosmidomycin. Experimental Parasitology. 2007;116(4): 375-384.
McLeod R, Muench SP, Rafferty JB, Kyle DE, Mui EJ, Kirisits MJ, Dorris M. Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of Apicomplexan Fab I. International Journal for Parasitology. 2001;31(2):109-113.
Waller RF, Keeling PJ, Donald RG, Striepen B, Handman E, Lang-Unnasch N, McFadden GI. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proceedings of the National Academy of Sciences. 1998;95(21):12352-12357.
Zuther E, Johnson JJ, Haselkorn R, McLeod R, Gornicki P. Growth of Toxoplasma gondii is inhibited by aryloxy-phenoxypropionate herbicides targeting acetyl-CoA carboxylase. Proceedings of the National Academy of Sciences. 1999; 96(23):13387-13392.
Gozalbes R, Brun-Pascaud M, Garcia-Domenech R, Galvez J, Girard PM, Doucet JP, Derouin F. Anti-toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: Prediction of activity by molecular topology and virtual computational techniques. Antimicrobial Agents and Chemo-therapy. 2000;44(10):2771- 2776.
Divo AA, Sartorelli AC, Patton CL, Bia FJ. Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrobial Agents and Chemotherapy. 1988;32(8):1182-1186.
Woods KM, Nesterenko MV, Upton SJ. Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro. Annals of Tropical Medicine & Parasitology. 1996; 90(6):603-615.
García-Estrada C, Prada CF, Fernández-Rubio C, Rojo-Vázquez F, Balaña-Fouce R. DNA topoisomerases in apicomplexan parasites: Promising targets for drug discovery. Proceedings of the Royal Society of London B: Biological Sciences. 2010;277(1689):1777-1787.
Maxwell A. DNA gyrase as a drug target. Trends in Microbiology. 1997;5(3):102-109.
McFadden GI, Roos DS. Apicomplexan plastids as drug targets. Trends in Microbiology. 1999;7(8):328-333.
Khan AA, Slifer T, Araujo FG, Remington JS. Trovafloxacin is active against Toxoplasma gondii. Antimicrobial agents and Chemotherapy. 1996;40(8):1855-1859.
Ralph SA, D'Ombrain MC, McFadden GI. The apicoplast as an antimalarial drug target. Drug Resistance Updates. 2001; 4(3):145-151.
Reiff SB, Vaishnava S, Striepen B. The HU protein is important for apicoplast genome maintenance and inheritance in Toxoplasma gondii. Eukaryotic Cell. 2012; 11(7):905-915.
Lüder CG, Seeber F. Toxoplasma. In molecular parasitology. Springer, Vienna. 2016;217-239.
Pfefferkorn ER, Nothnagel RF, Borotz SE. Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrobial Agents and Chemotherapy. 1992;36(5):1091-1096.
Shanmugam D, Wu B, Ramirez U, Jaffe EK, Roos DS. Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii kinetic and structural properties validate therapeutic potential. Journal of Biological Chemistry. 2010; 285(29):22122-22131.
van Dooren GG, Kennedy AT, McFadden GI. The use and abuse of heme in apicomplexan parasites. Antioxidants & Redox Signaling. 2012;17(4):634-656.
Sun H, Zhuo X, Zhao X, Yang Y, Chen X, Yao C, Du A. The heat shock protein 90 of Toxoplasma gondii is essential for invasion of host cells and tachyzoite growth. Parasite. 2017;24.
Ashwinder K, Kho MT, Chee PM, Lim WZ, Yap IK, Choi SB, Yam WK. Targeting heat shock proteins 60 and 70 of Toxoplasma gondii as a potential drug target: In silico approach. Interdisciplinary Sciences: Computational Life Sciences. 2016;8(4): 374-387.
Toursel C, Dzierszinski F, Bernigaud A, Mortuaire M, Tomavo S. Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii. Molecular and Biochemical Parasitology. 2000;111(2): 319-332.
Dobbin CA, Smith NC, Johnson AM. Heat shock protein 70 is a potential virulence factor in murine Toxoplasma infection via immunomodulation of host NF-κB and nitric oxide. The Journal of Immunology. 2002;169(2):958-965.
Müller S, Liebau E, Walter RD, Krauth-Siegel RL. Thiol-based redox metabolism of protozoan parasites. Trends in Parasitology. 2003;19(7):320-328.
Weiss LM, Kim K. The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci. 2011;5:D391-D405.
Denton H, Robert CW, Alexander J, Thong KW, Coombs GH. Enzymes of energy metabolism in the bradyzoite and tachyzoites of Toxoplasma gondii. FEMS Microbio Lett. 1996;137:103-8.
Al-Anouti F, Tomavo S, Parmley S, Ananvoranich S. The expression of lactate dehydrogenase is important for the cell cycle of Toxoplasma gondii. Journal of Biological Chemistry. 2004;279(50):52300-52311.
Abdelbaset AE, Fox BA, Karram MH, Ellah MRA, Bzik DJ, Igarashi M. Lactate dehydrogenase in Toxoplasma gondii controls virulence, bradyzoite differentiation and chronic infection. PloS One. 2017; 12(3):e0173745.
Kim YA, Sharon A, Chu CK, Rais RH, Al Safarjalani ON, Naguib FN, el Kouni MH. Structure− activity relationships of 7-deaza-6-benzylthioinosine analogues as ligands of Toxoplasma gondii adenosine kinase. Journal of Medicinal Chemistry. 2008;51(13):3934-3945.
Blume M, Nitzsche R, Sternberg U, Gerlic M, Masters SL, Gupta N, McConville MJ. A Toxoplasma gondii gluconeogenic enzyme contributes to robust central carbon metabolism and is essential for replication and virulence. Cell Host & Microbe. 2015; 18(2):210-220.
Coppens I, Sinai AP, Joiner KA. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated en ocytosis for cholesterol acquisition. J Cell Bio. 2000;149:167-180.
Sanfelice RA, da Silva SS, Bosqui LR, Miranda-Sapla MM, Barbosa BF, Silva RJ, Conchon-Costa I. Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells. Acta Tropica. 2017; 167:208-215.
Gupta Nishith, Matthew M. Zahn, Isabelle Coppens, Keith A. Joiner, Dennis R. Voelker. Selective disruption of phos-phatidylcholine metabolism of the intracellular parasite Toxoplasma gondii arrests its growth. The Journal of Biological Chemistry. 2005;280(16): 16345–16353.
Ancelin ML, Vial HJ. Quartenary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport. Anti-microbial Agents and Chemotherapy. 1986;29(5):814-820.
Tipparaju SK, Muench SP, Mui EJ, Ruzheinikov SN, Lu JZ, Hutson SL, Kozikowski AP. Identification and develop-ment of novel inhibitors of Toxoplasma gondii enoyl reductase. Journal of Medicinal Chemistry. 2010;53(17):6287-6300.
Cheng G, Muench SP, Zhou Y, Afanador GA, Mui EJ, Fomovska A, Hickman MR. Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase. Bioorganic & Medicinal Chemistry Letters. 2013;23(7):2035-2043.
-
Abstract View: 2165 times
PDF Download: 651 times
