Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter

Molecular Microbiology

Volumn 97, Issue 2, 2015, Pages 381-395

  Petersen, Ines ^a,b   Gabryszewski, Stanislaw J ^a   Johnston, Geoffrey L ^a,c   Dhingra, Satish K ^a,d   Ecker, Andrea ^a   Lewis, Rebecca E ^a   de Almeida, Mariana Justino ^a   Straimer, Judith ^a   Henrich, Philipp P ^a   Palatulan, Eugene ^a   Johnson, David J ^a   Coburn Flynn, Olivia ^a   Sanchez, Cecilia ^b   Lehane, Adele M ^a,e   Lanzer, Michael ^b   Fidock, David A ^a  

^a Department of Medicine   (United States)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c Columbia University ^*  (United States)

^d BINGHAMTON UNIVERSITY   (United States)

^e AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ARTEMISININ; BENFLUMETOL; CHLOROQUINE; CARRIER PROTEIN; PFCRT PROTEIN, PLASMODIUM FALCIPARUM; PROTOZOAL PROTEIN;

ANTIMALARIAL DRUG RESISTANCE; ARTICLE; CAMBODIA; COCULTURE; CONTROLLED STUDY; CROSS RESISTANCE; GENE EXPRESSION; GENE FREQUENCY; GENE LOCUS; GENETIC ENGINEERING; GENETIC VARIABILITY; HAPLOTYPE; IC50; IN VITRO STUDY; MICROBIAL GROWTH; NONHUMAN; PHILIPPINES; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; DRUG EFFECTS; DRUG RESISTANCE; ERYTHROCYTE; GENETICS; HUMAN; MALARIA FALCIPARUM; METABOLISM; MUTATION; PARASITOLOGY;

PLASMODIUM FALCIPARUM;

CHLOROQUINE; DRUG RESISTANCE; ERYTHROCYTES; GENE FREQUENCY; HAPLOTYPES; HUMANS; MALARIA, FALCIPARUM; MEMBRANE TRANSPORT PROTEINS; MUTATION; PLASMODIUM FALCIPARUM; PROTOZOAN PROTEINS;

EID: 84935754128     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/mmi.13035     Document Type: Article

References (86)

1. Alifrangis, M., Dalgaard, M.B., Lusingu, J.P., Vestergaard, L.S., Staalsoe, T., Jensen, A.T., etal. (2006) Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania. J Infect Dis 193: 1738-1741.
2. Ariey, F., Fandeur, T., Durand, R., Randrianarivelojosia, M., Jambou, R., Legrand, E., etal. (2006) Invasion of Africa by a single pfcrt allele of South East Asian type. Malar J 5: 34.
3. Ariey, F., Witkowski, B., Amaratunga, C., Beghain, J., Langlois, A.C., Khim, N., etal. (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50-55.
4. Baro, N.K., Callaghan, P.S., and Roepe, P.D. (2013) Function of resistance conferring Plasmodium falciparum chloroquine resistance transporter isoforms. Biochemistry 52: 4242-4249.
5. Bellanca, S., Summers, R.L., Meyrath, M., Dave, A., Nash, M.N., Dittmer, M., etal. (2014) Multiple drugs compete for transport via the Plasmodium falciparum chloroquine resistance transporter at distinct but interdependent sites. J Biol Chem 289: 36336-36351.
6. Beshir, K., Sutherland, C.J., Merinopoulos, I., Durrani, N., Leslie, T., Rowland, M., and Hallett, R.L. (2010) Amodiaquine resistance in Plasmodium falciparum malaria in Afghanistan is associated with the pfcrt SVMNT allele at codons 72 to 76. Antimicrob Agents Chemother 54: 3714-3716.
7. Brown, K.M., Costanzo, M.S., Xu, W., Roy, S., Lozovsky, E.R., and Hartl, D.L. (2010) Compensatory mutations restore fitness during the evolution of dihydrofolate reductase. Mol Biol Evol 27: 2682-2690.
8. Cabrera, M., Paguio, M.F., Xie, C., and Roepe, P.D. (2009) Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity. Biochemistry 48: 11152-11154.
9. Chen, N., Kyle, D.E., Pasay, C., Fowler, E.V., Baker, J., Peters, J.M., and Cheng, Q. (2003) pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines. Antimicrob Agents Chemother 47: 3500-3505.
10. Chen, N., Wilson, D.W., Pasay, C., Bell, D., Martin, L.B., Kyle, D., and Cheng, Q. (2005) Origin and dissemination of chloroquine-resistant Plasmodium falciparum with mutant pfcrt alleles in the Philippines. Antimicrob Agents Chemother 49: 2102-2105.
11. Chen, N., Gao, Q., Wang, S., Wang, G., Gatton, M., and Cheng, Q. (2008) No genetic bottleneck in Plasmodium falciparum wild-type pfcrt alleles reemerging in Hainan Island, China, following high-level chloroquine resistance. Antimicrob Agents Chemother 52: 345-347.
12. Cooper, R.A., Ferdig, M.T., Su, X.Z., Ursos, L.M., Mu, J., Nomura, T., etal. (2002) Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum. Mol Pharmacol 61: 35-42.
13. Cooper, R.A., Lane, K.D., Deng, B., Mu, J., Patel, J.J., Wellems, T.E., etal. (2007) Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine. Mol Microbiol 63: 270-282.
14. Dondorp, A.M., Fairhurst, R.M., Slutsker, L., Macarthur, J.R., Breman, J.G., Guerin, P.J., etal. (2011) The threat of artemisinin-resistant malaria. N Engl J Med 365: 1073-1075.
15. Durrand, V., Berry, A., Sem, R., Glaziou, P., Beaudou, J., and Fandeur, T. (2004) Variations in the sequence and expression of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and their relationship to chloroquine resistance in vitro. Mol Bochem Parasitol 136: 273-285.
16. Eastman, R.T., and Fidock, D.A. (2009) Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol 7: 864-874.
17. Eastman, R.T., Dharia, N.V., Winzeler, E.A., and Fidock, D.A. (2011) Piperaquine resistance is associated with a copy number variation on chromosome 5 in drug-pressured Plasmodium falciparum parasites. Antimicrob Agents Chemother 55: 3908-3916.
18. Ecker, A., Lakshmanan, V., Sinnis, P., Coppens, I., and Fidock, D.A. (2011) Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes. J Infect Dis 203: 228-236.
19. Ecker, A., Lehane, A.M., Clain, J., and Fidock, D.A. (2012) PfCRT and its role in antimalarial drug resistance. Trends Parasitol 28: 504-514.
20. Ekland, E.H., and Fidock, D.A. (2008) In vitro evaluations of antimalarial drugs and their relevance to clinical outcomes. Int J Parasitol 38: 743-747.
21. Ferdig, M.T., Cooper, R.A., Mu, J., Deng, B., Joy, D., Su, X.Z., and Wellems, T.E. (2004) Dissecting the loci of low-level quinine resistance in malaria parasites. Mol Microbiol 52: 985-997.
22. Fidock, D.A., Nomura, T., and Wellems, T.E. (1998) Cycloguanil and its parent compound proguanil demonstrate distinct activities against Plasmodium falciparum malaria parasites transformed with human dihydrofolate reductase. Mol Pharmacol 54: 1140-1147.
23. Fidock, D.A., Nomura, T., Talley, A.K., Cooper, R.A., Dzekunov, S.M., Ferdig, M.T., etal. (2000) Mutations in the P.falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6: 861-871.
24. Fitch, C.D. (2004) Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci 74: 1957-1972.
25. Frosch, A.E., Venkatesan, M., and Laufer, M.K. (2011) Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data. Malar J 10: 116.
26. Gama, B.E., Pereira-Carvalho, G.A., Lutucuta Kosi, F.J., Almeida de Oliveira, N.K., Fortes, F., Rosenthal, P.J., etal. (2010) Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene. Malar J 9: 174.
27. Gaviria, D., Paguio, M.F., Turnbull, L.B., Tan, A., Siriwardana, A., Ghosh, D., etal. (2013) A process similar to autophagy is associated with cytocidal chloroquine resistance in Plasmodium falciparum. PLoS ONE 8: e79059.
28. Gligorijevic, B., Purdy, K., Elliott, D.A., Cooper, R.A., and Roepe, P.D. (2008) Stage independent chloroquine resistance and chloroquine toxicity revealed via spinning disk confocal microscopy. Mol Biochem Parasitol 159: 7-23.
29. Griffing, S., Syphard, L., Sridaran, S., McCollum, A.M., Mixson-Hayden, T., Vinayak, S., etal. (2010) pfmdr1 amplification and fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum in Venezuela. Antimicrob Agents Chemother 54: 1572-1579.
30. Hastings, I.M., and Donnelly, M.J. (2005) The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance. Drug Resist Updat 8: 43-50.
31. Hrycyna, C.A., Summers, R.L., Lehane, A.M., Pires, M.M., Namanja, H., Bohn, K., etal. (2014) Quinine dimers are potent inhibitors of the Plasmodium falciparum chloroquine resistance transporter and are active against quinoline-resistant P.falciparum. ACS Chem Biol 9: 722-730.
32. Isozumi, R., Uemura, H., Le, D.D., Truong, V.H., Nguyen, D.G., Ha, V.V., etal. (2010) Longitudinal survey of Plasmodium falciparum infection in Vietnam: characteristics of antimalarial resistance and their associated factors. J Clin Microbiol 48: 70-77.
33. Juliano, J.J., Kwiek, J.J., Cappell, K., Mwapasa, V., and Meshnick, S.R. (2007) Minority-variant pfcrt K76T mutations and chloroquine resistance, Malawi. Emerg Infect Dis 13: 872-877.
34. Kidgell, C., Volkman, S.K., Daily, J., Borevitz, J.O., Plouffe, D., Zhou, Y., etal. (2006) A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog 2: e57.
35. Krogstad, D.J., Gluzman, I.Y., Kyle, D.E., Oduola, A.M., Martin, S.K., Milhous, W.K., and Schlesinger, P.H. (1987) Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science 238: 1283-1285.
36. Kublin, J.G., Cortese, J.F., Njunju, E.M., Mukadam, R.A., Wirima, J.J., Kazembe, P.N., etal. (2003) Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870-1875.
37. Lakshmanan, V., Bray, P.G., Verdier-Pinard, D., Johnson, D.J., Horrocks, P., Muhle, R.A., etal. (2005) A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance. EMBO J 24: 2294-2305.
38. Laufer, M.K., Takala-Harrison, S., Dzinjalamala, F.K., Stine, O.C., Taylor, T.E., and Plowe, C.V. (2010) Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites. J Infect Dis 202: 801-808.
39. Levin, B.R., Perrot, V., and Walker, N. (2000) Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria. Genetics 154: 985.
40. Lewis, I.A., Wacker, M., Olszewski, K.L., Cobbold, S.A., Baska, K.S., Tan, A., etal. (2014) Metabolic QTL analysis links chloroquine resistance in Plasmodium falciparum to impaired hemoglobin catabolism. PLoS Genet 10: e1004085.
41. Maree, A.F., Keulen, W., Boucher, C.A., and De Boer, R.J. (2000) Estimating relative fitness in viral competition experiments. J Virol 74: 11067-11072.
42. Martin, R.E., Marchetti, R.V., Cowan, A.I., Howitt, S.M., Broer, S., and Kirk, K. (2009) Chloroquine transport via the malaria parasite's chloroquine resistance transporter. Science 325: 1680-1682.
43. Martin, S.K., Oduola, A.M., and Milhous, W.K. (1987) Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science 235: 899-901.
44. Mehlotra, R.K., Fujioka, H., Roepe, P.D., Janneh, O., Ursos, L.M., Jacobs-Lorena, V., etal. (2001) Evolution of a unique Plasmodium falciparum chloroquine-resistance phenotype in association with pfcrt polymorphism in Papua New Guinea and South America. Proc Natl Acad Sci USA 98: 12689-12694.
45. Mharakurwa, S., Sialumano, M., Liu, K., Scott, A., and Thuma, P. (2013) Selection for chloroquine-sensitive Plasmodium falciparum by wild Anopheles arabiensis in Southern Zambia. Malar J 12: 453.
46. Mita, T., Kaneko, A., Lum, J.K., Bwijo, B., Takechi, M., Zungu, I., etal. (2003) Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg 68: 413-415.
47. Mita, T., Kaneko, A., Lum, J., Zungu, I., Tsukahara, T., Eto, H., etal. (2004) Expansion of wild type allele rather than back mutation in pfcrt explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi. Mol Biochem Parasitol 135: 159-163.
48. Mitchell-Olds, T., Willis, J.H., and Goldstein, D.B. (2007) Which evolutionary processes influence natural genetic variation for phenotypic traits? Nat Rev Genet 8: 845-856.
49. Mixson-Hayden, T., Jain, V., McCollum, A.M., Poe, A., Nagpal, A.C., Dash, A.P., etal. (2010) Evidence of selective sweeps in genes conferring resistance to chloroquine and pyrimethamine in Plasmodium falciparum isolates in India. Antimicrob Agents Chemother 54: 997-1006.
50. Mu, J., Myers, R.A., Jiang, H., Liu, S., Ricklefs, S., Waisberg, M., etal. (2010) Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet 42: 268-271.
51. Mwai, L., Ochong, E., Abdirahman, A., Kiara, S.M., Ward, S., Kokwaro, G., etal. (2009) Chloroquine resistance before and after its withdrawal in Kenya. Malar J 8: 106.
52. Nash, D., Nair, S., Mayxay, M., Newton, P.N., Guthmann, J.P., Nosten, F., and Anderson, T.J. (2005) Selection strength and hitchhiking around two anti-malarial resistance genes. Proc Biol Sci 272: 1153-1161.
53. Olliaro, P., and Mussano, P. (2000) Amodiaquine for treating malaria. Cochrane Database Syst Rev (2): CD000016.
54. Ord, R., Alexander, N., Dunyo, S., Hallett, R., Jawara, M., Targett, G., etal. (2007) Seasonal carriage of pfcrt and pfmdr1 alleles in Gambian Plasmodium falciparum imply reduced fitness of chloroquine-resistant parasites. J Infect Dis 196: 1613-1619.
55. Osman, M.E., Mockenhaupt, F.P., Bienzle, U., Elbashir, M.I., and Giha, H.A. (2007) Field-based evidence for linkage of mutations associated with chloroquine (pfcrt/pfmdr1) and sulfadoxine-pyrimethamine (pfdhfr/pfdhps) resistance and for the fitness cost of multiple mutations in P.falciparum. Infect Genet Evol 7: 52-59.
56. Park, D.J., Lukens, A.K., Neafsey, D.E., Schaffner, S.F., Chang, H.H., Valim, C., etal. (2012) Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite. Proc Natl Acad Sci USA 109: 13052-13057.
57. Pascual, A., Madamet, M., Bertaux, L., Amalvict, R., Benoit, N., Travers, D., etal. (2013) In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene. Malar J 12: 431.
58. Patel, J.J., Thacker, D., Tan, J.C., Pleeter, P., Checkley, L., Gonzales, J.M., etal. (2010) Chloroquine susceptibility and reversibility in a Plasmodium falciparum genetic cross. Mol Microbiol 78: 770-787.
59. Price, R.N., Tjitra, E., Guerra, C.A., Yeung, S., White, N.J., and Anstey, N.M. (2007) Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 79-87.
60. Rosario, V.E., Hall, R., Walliker, D., and Beale, G.H. (1978) Persistence of drug-resistant malaria parasites. Lancet 1: 185-187.
61. Rosenthal, P.J. (2013) The interplay between drug resistance and fitness in malaria parasites. Mol Microbiol 89: 1025-1038.
62. Sa, J.M., and Twu, O. (2010) Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type. Malar J 9: 374.
63. Sa, J.M., Twu, O., Hayton, K., Reyes, S., Fay, M.P., Ringwald, P., and Wellems, T.E. (2009) Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine. Proc Natl Acad Sci USA 106: 18883-18889.
64. Saliba, K.J., Folb, P.I., and Smith, P.J. (1998) Role for the Plasmodium falciparum digestive vacuole in chloroquine resistance. Biochem Pharmacol 56: 313-320.
65. Sanchez, C.P., Stein, W., and Lanzer, M. (2003) Trans stimulation provides evidence for a drug efflux carrier as the mechanism of chloroquine resistance in Plasmodium falciparum. Biochemistry 42: 9383-9394.
66. Sanchez, C.P., Mayer, S., Nurhasanah, A., Stein, W.D., and Lanzer, M. (2011) Genetic linkage analyses redefine the roles of PfCRT and PfMDR1 in drug accumulation and susceptibility in Plasmodium falciparum. Mol Microbiol 82: 865-878.
67. Sanchez, C.P., Liu, C.H., Mayer, S., Nurhasanah, A., Cyrklaff, M., Mu, J., etal. (2014) A HECT ubiquitin-protein ligase as a novel candidate gene for altered quinine and quinidine responses in Plasmodium falciparum. PLoS Genet 10: e1004382.
68. Sidhu, A.B., Verdier-Pinard, D., and Fidock, D.A. (2002) Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298: 210-213.
69. Sisowath, C., Petersen, I., Veiga, M.I., Mortensson, A., Premji, Z., Bjorkman, A., etal. (2009) In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis 199: 750-757.
70. Snow, R.W., Trape, J.F., and Marsh, K. (2001) The past, present and future of childhood malaria mortality in Africa. Trends Parasitol 17: 593-597.
71. Straimer, J., Lee, M.C., Lee, A.H., Zeitler, B., Williams, A.E., Pearl, J.R., etal. (2012) Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleases. Nat Methods 9: 993-998.
72. Straimer, J., Gnadig, N.F., Witkowski, B., Amaratunga, C., Duru, V., Ramadani, A.P., etal. (2015) Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428-431.
73. Su, X., Kirkman, L.A., Fujioka, H., and Wellems, T.E. (1997) Complex polymorphisms in an approximately 330kDa protein are linked to chloroquine-resistant P.falciparum in Southeast Asia and Africa. Cell 91: 593-603.
74. Summers, R.L., Dave, A., Dolstra, T.J., Bellanca, S., Marchetti, R.V., Nash, M.N., etal. (2014) Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite's chloroquine resistance transporter. Proc Natl Acad Sci USA 111: E1759-E1767.
75. Trape, J.F. (2001) The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64: 12-17.
76. Valderramos, S.G., and Fidock, D.A. (2006) Transporters involved in resistance to antimalarial drugs. Trends Pharmacol Sci 27: 594-601.
77. Valderramos, S.G., Valderramos, J.C., Musset, L., Purcell, L.A., Mercereau-Puijalon, O., Legrand, E., and Fidock, D.A. (2010) Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum. PLoS Pathog 6: e1000887.
78. Volkman, S., Sabeti, P., Decaprio, D., Neafsey, D., Schaffner, S., Milner, D., etal. (2007) A genome-wide map of diversity in Plasmodium falciparum. Nat Genet 39: 113-119.
79. Walliker, D., Hunt, P., and Babiker, H. (2005) Fitness of drug-resistant malaria parasites. Acta Trop 94: 251-259.
80. Wang, X., Mu, J., Li, G., Chen, P., Guo, X., Fu, L., etal. (2005) Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P.falciparum malaria in Hainan, People's Republic of China. Am J Trop Med Hyg 72: 410-414.
81. Wellems, T.E., and Plowe, C.V. (2001) Chloroquine-resistant malaria. J Infect Dis 184: 770-776.
82. Wellems, T.E., Panton, L.J., Gluzman, I.Y., do Rosario, V.E., Gwadz, R.W., Walker-Jonah, A., and Krogstad, D.J. (1990) Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature 345: 253-255.
83. Wells, T.N., Alonso, P.L., and Gutteridge, W.E. (2009) New medicines to improve control and contribute to the eradication of malaria. Nat Rev Drug Discov 8: 879-891.
84. White, N.J. (2008) Qinghaosu (artemisinin): the price of success. Science 320: 330-334.
85. WHO (2014) World Malaria Report 2014. URL http://www.who.int/malaria/publications/world_malaria_report_2014/report/en
86. Wootton, J.C., Feng, X., Ferdig, M.T., Cooper, R.A., Mu, J., Baruch, D.I., etal. (2002) Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418: 320-323.