An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei

PLoS Pathogens

Volumn 11, Issue 5, 2015, Pages

  de Macêdo, Juan P ^a   Schumann Burkard, Gabriela ^a   Niemann, Moritz ^a   Barrett, Michael P ^b   Vial, Henri ^c   Mäser, Pascal ^d,e   Roditi, Isabel ^a   Schneider, André ^a   Bütikofer, Peter ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

^c UNIVERSITÉ DE MONTPELLIER   (France)

^d SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^e UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CHOLINE DERIVATIVE; G25; GLUCOSE; LIOTHYRONINE; MESSENGER RNA; PENTAMIDINE; PROLINE; PROTEIN; PYRROLINE 5 CARBOXYLATE DEHYDROGENASE; T4; TBMCP14; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT ANION CHANNEL; ANTITRYPANOSOMAL AGENT; CARRIER PROTEIN; DELTA-1-PYRROLINE-5-CARBOXYLATE; PROTOZOAL PROTEIN; PYRROLE DERIVATIVE; RECOMBINANT PROTEIN;

ARTICLE; DRUG MECHANISM; DRUG SENSITIVITY; ENERGY METABOLISM; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; GENE SILENCING; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; RNA INTERFERENCE; TRYPANOSOMA BRUCEI; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENE INACTIVATION; GENETICS; METABOLISM; METABOLOMICS; MITOCHONDRION; MULTIDRUG RESISTANCE; PROTEIN TERTIARY STRUCTURE; TRANSPORT AT THE CELLULAR LEVEL; TRYPANOSOMA BRUCEI BRUCEI;

MAMMALIA; TRYPANOSOMA BRUCEI; TRYPANOSOMATIDAE;

BIOLOGICAL TRANSPORT; CELL PROLIFERATION; DRUG RESISTANCE, MULTIPLE; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GENE KNOCKOUT TECHNIQUES; MEMBRANE POTENTIAL, MITOCHONDRIAL; METABOLOMICS; MITOCHONDRIA; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; PARASITIC SENSITIVITY TESTS; PENTAMIDINE; PROLINE; PROTEIN STRUCTURE, TERTIARY; PROTOZOAN PROTEINS; PYRROLES; RECOMBINANT PROTEINS; RNA INTERFERENCE; TRYPANOCIDAL AGENTS; TRYPANOSOMA BRUCEI BRUCEI;

EID: 84930343963     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1004875     Document Type: Article

References (66)

1. (1998) A field guide for the diagnosis, treatment and prevention of African animal Trypanosomosis. Food and Agriculture Organization (FAO) http://www.fao.org/docrep/006/x0413e/X0413E00.htm#TOC (accessed in: May.2014).
2. Brun R, Blum J, Chappuis F, Burri C, (2010) Human African trypanosomiasis. Lancet 375: 148–159. doi: 10.1016/S0140-6736(09)60829-1 19833383
3. Rollo IM, Williamson J, (1951) Acquired resistance to 'Melarsen', tryparsamide and amidines in pathogenic trypanosomes after treatment with 'Melarsen' alone. Nature 167: 147–148. 14806401
4. de Koning HP, (2008) Ever-increasing complexities of diamidine and arsenical crossresistance in African trypanosomes. Trends Parasitol 24: 345–349. doi: 10.1016/j.pt.2008.04.006 18599351
5. Mäser P, Sütterlin C, Kralli A, Kaminsky R, (1999) A nucleoside transporter from Trypanosoma brucei involved in drug resistance. Science 285: 242–244. 10398598
6. Baker N, Glover L, Munday JC, Aguinaga Andrés D, Barrett MP, et al. (2012) Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes. Proc Natl Acad Sci USA 109: 10996–11001. doi: 10.1073/pnas.1202885109 22711816
7. Vincent IM, Creek DJ, Watson DG, Kamleh MA, Woods DJ, et al. (2010) A molecular mechanism for eflornithine resistance in African trypanosomes. PLoS Pathogens 6(11): e1001204. doi: 10.1371/journal.ppat.1001204 21124824
8. Baker N, Alsford S, Horn D, (2011) Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6. Mol Biochem Parasitol 176: 55–57. doi: 10.1016/j.molbiopara.2010.11.010 21093499
9. Schumann Burkard G, Jutzi P, Roditi I, (2011) Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters. Mol Biochem Parasitol 175: 91–94. doi: 10.1016/j.molbiopara.2010.09.002 20851719
10. Munday JC, Eze AA, Baker N, Glover L, Clucas C, et al. (2014) Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs. J Antimicrob Chemother 69: 651–663. doi: 10.1093/jac/dkt442 24235095
11. Lanteri CA, Stewart ML, Brock JM, Alibu VP, Meshnick SR, et al. (2006) Roles for the Trypanosoma brucei P2 transporter in DB75 uptake and resistance. Mol Pharmacol 70: 1585–1592. 16912218
12. Lüscher A, Onal P, Schweingruber A-M, Mäser P, (2007) Adenosine kinase of Trypanosoma brucei and its role in susceptibility to adenosine antimetabolites. Antimicrob Agents Chemother 51: 3895–3901. 17698621
13. Matovu E, Stewart ML, Geiser F, Brun R, Mäser P, et al. (2003) Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei. Eukaryotic Cell 2: 1003–1008. 14555482
14. Agbe A, Yielding KL, (1995) Kinetoplasts play an important role in the drug responses of Trypanosoma brucei. J Parasitol 81: 968–973. 8544073
15. Lanteri CA, Tidwell RR, Meshnick SR, (2008) The mitochondrion is a site of trypanocidal action of the aromatic diamidine DB75 in bloodstream forms of Trypanosoma brucei. Antimicrob Agents Chemother 52: 875–882. 18086841
16. Gould MK, Schnaufer AC, (2014) Independence from Kinetoplast DNA maintenance and expression is associated with multidrug resistance in Trypanosoma brucei in vitro. Antimicrobial Agents Chemother 58: 2925–2928. doi: 10.1128/AAC.00122-14 24550326
17. Smith TK, Bütikofer P, (2010) Lipid metabolism in Trypanosoma brucei. Mol Biochem Parasitol 172: 66–79. doi: 10.1016/j.molbiopara.2010.04.001 20382188
18. Patnaik PK, Field MC, Menon AK, Cross GA, Yee MC, et al. (1993) Molecular species analysis of phospholipids from Trypanosoma brucei bloodstream and procyclic forms. Mol Biochem Parasitol 58: 97–105. 8459838
19. Bowes AE, Samad AH, Jiang P, Weaver B, Mellors A, (1993) The acquisition of lysophosphatidylcholine by African trypanosomes. J Biol Chem 268: 13885–13892. 8314756
20. Macêdo JP, Schmidt RS, Mäser P, Rentsch D, Vial HJ, et al. (2013) Characterization of choline uptake in Trypanosoma brucei procyclic and bloodstream forms. Mol Biochem Parasitol 190: 16–22. doi: 10.1016/j.molbiopara.2013.05.007 23747277
21. Vial HJ, Ancelin ML, (1992) Malarial lipids. An overview. Subcell Biochem 18: 259–306. 1485354
22. Déchamps S, Shastri S, Wengelnik K, Vial HJ, (2010) Glycerophospholipid acquisition in Plasmodium—a puzzling assembly of biosynthetic pathways. Int J Parasitol 40: 1347–1365. doi: 10.1016/j.ijpara.2010.05.008 20600072
23. Ramakrishnan S, Serricchio M, Striepen B, Bütikofer P, (2013) Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans. Prog Lipid Res 52: 488–512. doi: 10.1016/j.plipres.2013.06.003 23827884
24. Déchamps S, Wengelnik K, Berry-Sterkers L, Cerdan R, Vial HJ, et al. (2010) The Kennedy phospholipid biosynthesis pathways are refractory to genetic disruption in Plasmodium berghei and therefore appear essential in blood stages. Mol Biochem Parasitol 173: 69–80. doi: 10.1016/j.molbiopara.2010.05.006 20478340
25. Biagini GA, Pasini EM, Hughes R, de Koning HP, Vial HJ, et al. (2004) Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs. Blood 104: 3372–3377. 15205262
26. Ancelin ML, Vial HJ, (1986) Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport. Antimicrob Agents Chemother 29: 814–820. 3524430
27. Calas M, Cordina G, Bompart J, Ben Bari M, Jei T, et al. (1997) Antimalarial activity of molecules interfering with Plasmodium falciparum phospholipid metabolism. Structure-activity relationship analysis. J Med Chem 40: 3557–3566. 9357523
28. Ancelin ML, Calas M, Vidal-Sailhan V, Herbuté S, Ringwald P, et al. (2003) Potent inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities. Antimicrob Agents Chemother 47: 2590–2597. 12878524
29. Ancelin ML, Calas M, Bompart J, Cordina G, Martin D, et al. (1998) Antimalarial activity of 77 phospholipid polar head analogs: close correlation between inhibition of phospholipid metabolism and in vitro Plasmodium falciparum growth. Blood 91: 1426–1437. 9454774
30. Wein S, Maynadier M, Bordat Y, Perez J, Maheshwari S, et al. (2012) Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate. Br J Pharmacol 166: 2263–2276. doi: 10.1111/j.1476-5381.2012.01966.x 22471905
31. Biagini GA, Richier E, Bray PG, Calas M, Vial H, et al. (2003) Heme binding contributes to antimalarial activity of bis-quaternary ammoniums. Antimicrob Agents Chemother 47: 2584–2589. 12878523
32. Roggero R, Zufferey R, Minca M, Richier E, Calas M, et al. (2004) Unraveling the mode of action of the antimalarial choline analog G25 in Plasmodium falciparum and Saccharomyces cerevisiae. Antimicrob Agents Chemother 48: 2816–2824. 15273086
33. Ibrahim HMS, Al-Salabi MI, El Sabbagh N, Quashie NB, Alkhaldi AAM, et al. (2011) Symmetrical choline-derived dications display strong anti-kinetoplastid activity. J Antimicrob Chemother 66: 111–125. doi: 10.1093/jac/dkq401 21078603
34. Wengelnik K, Vidal V, Ancelin ML, Cathiard A-M, Morgat JL, et al. (2002) A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science 295: 1311–1314. 11847346
35. Vial HJ, Wein S, Farenc C, Kocken C, Nicolas O, et al. (2004) Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc Natl Acad Sci USA 101: 15458–15463. 15492221
36. Colasante C, Peña Diaz P, Clayton C, Voncken F, (2009) Mitochondrial carrier family inventory of Trypanosoma brucei brucei: Identification, expression and subcellular localisation. Mol Biochem Parasitol 167: 104–117. doi: 10.1016/j.molbiopara.2009.05.004 19463859
37. Nilsson D, Gunasekera K, Mani J, Osteras M, Farinelli L, et al. (2010) Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei. PLoS Pathog 6(8): e1001037. doi: 10.1371/journal.ppat.1001037 20700444
38. Siegel TN, Hekstra DR, Wang X, Dewell S, Cross GA, (2010) Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Res 38: 4946–4957. doi: 10.1093/nar/gkq237 20385579
39. Peña-Diaz P, Pelosi L, Ebikeme C, Colasante C, Gao F, et al. (2012) Functional characterization of TbMCP5, a conserved and essential ADP/ATP carrier present in the mitochondrion of the human pathogen Trypanosoma brucei. J Biol Chem 287: 41861–41874. doi: 10.1074/jbc.M112.404699 23074217
40. Mathis AM, Holman JL, Sturk LM, Ismail MA, Boykin DW, et al. (2006) Accumulation and intracellular distribution of antitrypanosomal diamidine compounds DB75 and DB820 in African trypanosomes. Antimicrob Agents Chemother 50: 2185–2191. 16723581
41. Basselin M, Denise H, Coombs GH, Barrett MP, (2002) Resistance to pentamidine in Leishmania mexicana involves exclusion of the drug from the mitochondrion. Antimicrob Agents Chemother 46: 3731–3738. 12435669
42. Stewart ML, Krishna S, Burchmore RJS, Brun R, de Koning HP, et al. (2005) Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test. Lancet 366: 486–487. 16084257
43. Creek DJ, Anderson J, McConville MJ, Barrett MP, (2012) Metabolomic analysis of trypanosomatid protozoa. Mol Biochem Parasitol 181: 73–84. doi: 10.1016/j.molbiopara.2011.10.003 22027026
44. Lamour N, Rivière L, Coustou V, Coombs GH, Barrett MP, et al. (2005) Proline metabolism in procyclic Trypanosoma brucei is down-regulated in the presence of glucose. J Biol Chem 280: 11902–11910. 15665328
45. Tan THP, Pach R, Crausaz A, Ivens A, Schneider A, (2002) tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial import. Mol Cell Biol 22: 3707–3717. 11997507
46. Bochud-Allemann N, Schneider A, (2002) Mitochondrial substrate level phosphorylation is essential for growth of procyclic Trypanosoma brucei. J Biol Chem 277: 32849–32854. 12095995
47. Jain E, Bairoch A, Duvaud S, Phan I, Redaschi N, et al. (2009) Infrastructure for the life sciences: design and implementation of the UniProt website. BMC Bioinformatics 10: 136. doi: 10.1186/1471-2105-10-136 19426475
48. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ, (1990) Basic local alignment search tool. J Mol Biol 215: 403–410. 2231712
49. Edgar RC, (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797. 15034147
50. Aquila H, Link TA, Klingenberg M, (1987) Solute carriers involved in energy transfer of mitochondria form a homologous protein family. FEBS Lett 212: 1–9. 3026849
51. Saraste M, Walker JE, (1982) Internal sequence repeats and the path of polypeptide in mitochondrial ADP/ATP translocase. FEBS Lett 144: 250–254. 6288471
52. Palmieri F, Pierri CL, De Grassi A, Nunes-Nesi A, Fernie AR, (2011) Evolution, structure and function of mitochondrial carriers: a review with new insights. Plant J 66: 161–181. doi: 10.1111/j.1365-313X.2011.04516.x 21443630
53. Cross GA, Klein RA, Linstead DJ, (1975) Utilization of amino acids by Trypanosoma brucei in culture: L-threonine as a precursor for acetate. Parasitology 71: 311–326. 1187188
54. Wirtz E, Leal S, Ochatt C, Cross GA, (1999) A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei. Mol Biochem Parasitol 99: 89–101. 10215027
55. Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R, (1997) The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro. Acta Trop 68: 139–147. 9386789
56. Serricchio M, Bütikofer P, (2013) Phosphatidylglycerophosphate synthase associates with a mitochondrial inner membrane complex and is essential for growth of Trypanosoma brucei. Mol Microbiol 87: 569–579. doi: 10.1111/mmi.12116 23190171
57. Oberholzer M, Morand S, Kunz S, Seebeck T, (2006) A vector series for rapid PCR-mediated C-terminal in situ tagging of Trypanosoma brucei genes. Mol Biochem Parasitol 145: 117–120. 16269191
58. Lamb JR, Fu V, Wirtz E, Bangs JD, (2001) Functional analysis of the trypanosomal AAA protein TbVCP with trans-dominant ATP hydrolysis mutants. J Biol Chem 276: 21512–21520. 11279035
59. Allemann N, Schneider A, (2000) ATP production in isolated mitochondria of procyclic Trypanosoma brucei. Mol Biochem Parasitol 111: 87–94. 11087919
60. t’Kindt R, Jankevics A, Scheltema RA, Zheng L, Watson DG, et al. (2010) Towards an unbiased metabolic profiling of protozoan parasites: optimisation of a Leishmania sampling protocol for HILIC-orbitrap analysis. Anal Bioanal Chem 398: 2059–2069. doi: 10.1007/s00216-010-4139-0 20824428
61. Tautenhahn R, Böttcher C, Neumann S, (2008) Highly sensitive feature detection for high resolution LC/MS. BMC Bioinformatics 9: 504. doi: 10.1186/1471-2105-9-504 19040729
62. Scheltema RA, Jankevics A, Jansen RC, Swertz MA, Breitling R, (2011) PeakML/mzMatch: a file format, Java library, R library, and tool-chain for mass spectrometry data analysis. Anal Chem 83: 2786–2793. doi: 10.1021/ac2000994 21401061
63. Creek DJ, Jankevics A, Burgess KEV, Breitling R, Barrett MP, (2012) IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data. Bioinformatics 28: 1048–1049. doi: 10.1093/bioinformatics/bts069 22308147
64. Creek DJ, Jankevics A, Breitling R, Watson DG, Barrett MP, et al. (2011) Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction. Anal Chem 83: 8703–8710. doi: 10.1021/ac2021823 21928819
65. Eddy SR, (2011) Accelerated Profile HMM Searches. PLoS Comp Biol 7: e1002195. doi: 10.1371/journal.pcbi.1002195 22039361
66. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, et al. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 2731–2739. doi: 10.1093/molbev/msr121 21546353