Toxoplasma gondii Relies on Both Host and Parasite Isoprenoids and Can Be Rendered Sensitive to Atorvastatin

PLoS Pathogens

Volumn 9, Issue 10, 2013, Pages

  Li, Zhu Hong ^a   Ramakrishnan, Srinivasan ^a   Striepen, Boris ^a   Moreno, Silvia N J ^a  

^a UNIVERSITY OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; FARNESYL DIPHOSPHATE; FARNESYL TRANS TRANSFERASE; FOSMIDOMYCIN; GERANYLGERANYL PYROPHOSPHATE; GERANYLTRANSFERASE; ISOPRENOID; MEVALONIC ACID; ZOLEDRONIC ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DROWTH INHIBITION; DRUG POTENTIATION; HOST PARASITE INTERACTION; HUMAN; HUMAN CELL; IC 50; MOUSE; NONHUMAN; SOUTHERN BLOTTING; TACHYZOITE; THIN LAYER CHROMATOGRAPHY; TOXOPLASMA GONDII; TOXOPLASMOSIS; WESTERN BLOTTING;

ANIMALS; APICOPLASTS; DIPHOSPHATES; DITERPENES; FARNESYLTRANSTRANSFERASE; FEMALE; GENE KNOCKDOWN TECHNIQUES; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MICE; MICE, INBRED BALB C; POLYISOPRENYL PHOSPHATES; PROTOZOAN PROTEINS; PYRROLES; SESQUITERPENES; TOXOPLASMA; TOXOPLASMOSIS;

EID: 84887301097     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003665     Document Type: Article

References (43)

1. Israelski DM, Remington JS, (1993) Toxoplasmosis in patients with cancer. Clin Infect Dis 17 Suppl 2: S423-435.
2. Luft BJ, Hafner R, Korzun AH, Leport C, Antoniskis D, et al. (1993) Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. New Engl J Med 329: 995-1000.
3. Wong SY, Remington JS, (1994) Toxoplasmosis in pregnancy. Clin Infect Dis 18: 853-861; quiz 862.
4. Holland GN, (2004) Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophtalmol 137: 1-17.
5. Blader IJ, Manger ID, Boothroyd JC, (2001) Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells. J Biol Chem 276: 24223-24231.
6. Oldfield E, (2010) Targeting isoprenoid biosynthesis for drug discovery: bench to bedside. Accounts Chem Res 43: 1216-1226.
7. Nair SC, Brooks CF, Goodman CD, Strurm A, McFadden GI, et al. (2011) Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii. J Exp Med 208: 1547-1559.
8. Ling Y, Li ZH, Miranda K, Oldfield E, Moreno SN, (2007) The farnesyl-diphosphate/geranylgeranyl-diphosphate synthase of Toxoplasma gondii is a bifunctional enzyme and a molecular target of bisphosphonates. J Biol Chem 282: 30804-30816.
9. Jordao FM, Gabriel HB, Alves JM, Angeli CB, Bifano TD, et al. (2013) Cloning and characterization of bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase from Plasmodium falciparum. Malaria J 12: 184.
10. Szabo CM, Matsumura Y, Fukura S, Martin MB, Sanders JM, et al. (2002) Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J Med Chem 45: 2185-2196.
11. Ling Y, Sahota G, Odeh S, Chan JM, Araujo FG, et al. (2005) Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations. J Med Chem 48: 3130-3140.
12. Fox BA, Ristuccia JG, Gigley JP, Bzik DJ, (2009) Efficient gene replacements in Toxoplasma gondii strains deficient for nonhomologous end joining. Eukaryotic cell 8: 520-529.
13. Huynh MH, Carruthers VB, (2009) Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80. Euk Cell 8: 530-539.
14. Brooks CF, Johnsen H, van Dooren GG, Muthalagi M, Lin SS, et al. (2010) The toxoplasma apicoplast phosphate translocator links cytosolic and apicoplast metabolism and is essential for parasite survival. Cell Host Microbe 7: 62-73.
15. Mazumdar J, E HW, Masek K, C AH, Striepen B, (2006) Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. P Natl Acad Sci USA 103: 13192-13197.
16. Morisaki JH, Heuser JE, Sibley LD, (1995) Invasion of Toxoplasma gondii occurs by active penetration of the host cell. J Cell Sci 108 (Pt 6):: 2457-2464.
17. Meissner M, Schluter D, Soldati D, (2002) Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science 298: 837-840.
18. Francia ME, Wicher S, Pace DA, Sullivan J, Moreno SN, et al. (2011) A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion. Exper Cell Res 317: 1382-1396.
19. Urbina JA, Concepcion JL, Montalvetti A, Rodriguez JB, Docampo R, (2003) Mechanism of action of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the causative agent of Chagas' disease. Antimicrob Agents Ch 47: 2047-2050.
20. Coppens I, Sinai AP, Joiner KA, (2000) Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition. J Cell Biol 149: 167-180.
21. Robibaro B, Stedman TT, Coppens I, Ngo HM, Pypaert M, et al. (2002) Toxoplasma gondii Rab5 enhances cholesterol acquisition from host cells. Cell Microbiol 4: 139-152.
22. Charron AJ, Sibley LD, (2002) Host cells: mobilizable lipid resources for the intracellular parasite Toxoplasma gondii. J Cell Sci 115: 3049-3059.
23. Kozuki M, Kurata T, Miyazaki K, Morimoto N, Ohta Y, et al. (2011) Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-alpha. Brain Res 1388: 32-38.
24. Barone E, Cenini G, Di Domenico F, Martin S, Sultana R, et al. (2011) Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress in a preclinical model of Alzheimer disease: a novel mechanism of action. Pharmacol Res 63: 172-180.
25. Fox BA, Bzik DJ, (2002) De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii. Nature 415: 926-929.
26. Widler L, Jaeggi KA, Glatt M, Muller K, Bachmann R, et al. (2002) Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J Med Chem 45: 3721-3738.
27. Pillai SK, Moellering R.C. jr, and Eliopoulos G.M. (2005) Antibiotics in laboratory medicine; VLorian tE, editor. Philadelphia, PA.: Lippincott Williams & Wilkins Co.
28. Sabath LD, (1967) Synergy of antibacterial substances by apparently known mechanisms. Antimicrob Agents Ch 7: 210-217.
29. Garrod LP, Waterworth PM, (1962) Methods of testing combined antibiotic bactericidal action and the significance of the results. J Clin Pathol 15: 328-338.
30. Seeber F, Soldati-Favre D, (2010) Metabolic pathways in the apicoplast of apicomplexa. Int Rev Cell Mol Biol 281: 161-228.
31. Wiesner J, Reichenberg A, Heinrich S, Schlitzer M, Jomaa H, (2008) The plastid-like organelle of apicomplexan parasites as drug target. Curr Pharm Design 14: 855-871.
32. Nair SC, Striepen B, (2011) What do human parasites do with a chloroplast anyway? PLoS Biol 9: e1001137.
33. Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, et al. (1999) Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285: 1573-1576.
34. Baumeister S, Wiesner J, Reichenberg A, Hintz M, Bietz S, et al. (2011) Fosmidomycin uptake into Plasmodium and Babesia-infected erythrocytes is facilitated by parasite-induced new permeability pathways. PloS One 6: e19334.
35. Yeh E, DeRisi JL, (2011) Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. PLoS Biol 9: e1001138.
36. Okomo-Adhiambo M, Beattie C, Rink A, (2006) cDNA microarray analysis of host-pathogen interactions in a porcine in vitro model for Toxoplasma gondii infection. Infect Immun 74: 4254-4265.
37. Taoufiq Z, Pino P, N'Dilimabaka N, Arrouss I, Assi S, et al. (2011) Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage. Malaria J 10: 52.
38. Catron DM, Lange Y, Borensztajn J, Sylvester MD, Jones BD, et al. (2004) Salmonella enterica serovar Typhimurium requires nonsterol precursors of the cholesterol biosynthetic pathway for intracellular proliferation. Infect Immun 72: 1036-1042.
39. Krause BR, Princen HM, (1998) Lack of predictability of classical animal models for hypolipidemic activity: a good time for mice? Atherosclerosis 140: 15-24.
40. Vercesi AE, Rodrigues CO, Uyemura SA, Zhong L, Moreno SN, (1998) Respiration and oxidative phosphorylation in the apicomplexan parasite Toxoplasma gondii. J Biol Chem 273: 31040-31047.
41. MacRae JI, Sheiner L, Nahid A, Tonkin C, Striepen B, McConville MJ, (2012) Toxoplasma gondii depends on a complete 1 tricarboxylic acid cycle for intracellular growth and employs a GABA shunt to sustain extracellular motility. Cell Host Microbe 12: 682-692.
42. Pace DA, Fang J, Cintron R, Docampo MD, Moreno SN, (2011) Overexpression of a cytosolic pyrophosphatase (TgPPase) reveals a regulatory role of PP(i) in glycolysis for Toxoplasma gondii. Biochem J 440: 229-240.
43. Berenbaum MC, (1978) A method for testing for synergy with any number of agents. J Infect Dis 137: 122-130.