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Section: Evolutionary Biology
Topic: Evolution, Genetics/Genomics, Microbiology

Fitness costs and benefits in response to artificial artesunate selection in Plasmodium

Villa, Manon1; Berthomieu, Arnaud1 ; Rivero, Ana1  
1 MIVEGEC (CNRS, Université de Montpellier, IRD) – Montpellier, France

10.24072/pcjournal.200 - Peer Community Journal, Volume 2 (2022), article no. e74.

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Drug resistance is a major issue in the control of malaria. Mutations linked to drug resistance often target key metabolic pathways and are therefore expected to be associated with biological costs. The spread of drug resistance depends on the balance between the benefits that these mutations provide in the drug-treated host and the costs they incur in the untreated host. The latter may therefore be expressed both in the vertebrate host and in the vector. Research on the costs of drug resistance focusses on interactions with vertebrate host, yet whether they are also expressed in the vector has been overlooked. In this study, we aim to identify the costs and benefits of resistance against artesunate (AS), one of the main artemisinin derivatives used in malaria-endemic countries. For this purpose, we compared different AS-selected lines of the avian malaria parasite Plasmodium relictum to their ancestral (unselected) counterpart.  We tested their within host dynamics and virulence both in the vertebrate host and in its natural vector, the mosquito Culex quinquefasciatus. The within-host dynamics of the AS-selected lines in the treated birds was consistent with the phenotype of resistance described in human P. falciparum malaria: a clearance delay during the treatment followed by a recrudescence once the treatment was interrupted. In the absence of treatment, however, we found no significant costs of resistance in the bird. The results of the two experiments to establish the infectivity of the lines to mosquitoes point towards a decreased infectivity of the drug-selected lines as compared to the ancestral, reference one. We discuss the potential implication of these results on the spread of artesunate resistance in the field

Published online:
DOI: 10.24072/pcjournal.200
Type: Research article
Villa, Manon 1; Berthomieu, Arnaud 1; Rivero, Ana 1

1 MIVEGEC (CNRS, Université de Montpellier, IRD) – Montpellier, France
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights 
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Villa, Manon; Berthomieu, Arnaud; Rivero, Ana. Fitness costs and benefits in response to artificial artesunate selection in Plasmodium. Peer Community Journal, Volume 2 (2022), article  no. e74. doi : 10.24072/pcjournal.200. https://peercommunityjournal.org/articles/10.24072/pcjournal.200/

Peer reviewed and recommended by PCI : 10.24072/pci.evolbiol.100156

Conflict of interest of the recommender and peer reviewers:
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

[1] Babiker, H. A. Seasonal fluctuation of drug-resistant malaria parasites: a sign of fitness cost, Trends in Parasitology, Volume 25 (2009) no. 8, pp. 351-352 | DOI

[2] Beaudoin, R.; Strome, C.; Huff, C. Persistence of pyrimethamine resistance in the exoerythrocytic stages of Plasmodium gallinaceum, Experimental Parasitology, Volume 20 (1967) no. 2, pp. 156-159 | DOI

[3] Bolker, B. M. Ecological Models and Data in R, Princeton University Press, 2008 | DOI

[4] Coppée, R.; Jeffares, D. C.; Miteva, M. A.; Sabbagh, A.; Clain, J. Comparative structural and evolutionary analyses predict functional sites in the artemisinin resistance malaria protein K13, Scientific Reports, Volume 9 (2019) no. 1 | DOI

[5] Crawley, M. The R book, John Wiley & Sons, Chichester, 2007

[6] de Roode, J. C.; Culleton, R.; Bell, A. S.; Read, A. F. Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections, Malaria Journal, Volume 3 (2004) no. 1 | DOI

[7] de Roode, J. C.; Pansini, R.; Cheesman, S. J.; Helinski, M. E. H.; Huijben, S.; Wargo, A. R.; Bell, A. S.; Chan, B. H. K.; Walliker, D.; Read, A. F. Virulence and competitive ability in genetically diverse malaria infections, Proceedings of the National Academy of Sciences, Volume 102 (2005) no. 21, pp. 7624-7628 | DOI

[8] Dondorp, A. M.; Nosten, F.; Yi, P.; Das, D.; Phyo, A. P.; Tarning, J.; Lwin, K. M.; Ariey, F.; Hanpithakpong, W.; Lee, S. J.; Ringwald, P.; Silamut, K.; Imwong, M.; Chotivanich, K.; Lim, P.; Herdman, T.; An, S. S.; Yeung, S.; Singhasivanon, P.; Day, N. P.; Lindegardh, N.; Socheat, D.; White, N. J. Artemisinin Resistance in Plasmodium falciparum Malaria, New England Journal of Medicine, Volume 361 (2009) no. 5, pp. 455-467 | DOI

[9] Fairhurst, R. M. Understanding artemisinin-resistant malaria, Current Opinion in Infectious Diseases, Volume 28 (2015) no. 5, pp. 417-425 | DOI

[10] Greenberg, J. Mixed lethal strains of Plasmodium gallinaceum: Drug-sensitive, transferable (SP) × drug-resistant, non-transferable (BI), Experimental Parasitology, Volume 5 (1956) no. 4, pp. 359-370 | DOI

[11] Hastings, I.; Donnelly, M. The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance, Drug Resistance Updates, Volume 8 (2005) no. 1-2, pp. 43-50 | DOI

[12] Hewitt, R. Bird Malaria, American Journal of Hygiene, The American journal of hygiene; monographic series. no. 15., 1940

[13] Hott, A.; Tucker, M. S.; Casandra, D.; Sparks, K.; Kyle, D. E. Fitness of artemisinin-resistant Plasmodium falciparum in vitro, Journal of Antimicrobial Chemotherapy, Volume 70 (2015) no. 10, pp. 2787-2796 | DOI

[14] Huijben, S.; Nelson, W. A.; Wargo, A. R.; Sim, D. G.; Drew, D. R.; Read, A. F. Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites, Evolution (2010) | DOI

[15] Huijben, S.; Sim, D. G.; Nelson, W. A.; Read, A. F. The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection, Journal of Evolutionary Biology, Volume 24 (2011) no. 11, pp. 2410-2422 | DOI

[16] Koella, J. Costs and Benefits of Resistance against Antimalarial Drugs, Parasitology Today, Volume 14 (1998) no. 9, pp. 360-364 | DOI

[17] Laufer, M.; Plowe, C. Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies, Drug Resistance Updates, Volume 7 (2004) no. 4-5, pp. 279-288 | DOI

[18] Mathieu, L. C.; Cox, H.; Early, A. M.; Mok, S.; Lazrek, Y.; Paquet, J.-C.; Ade, M.-P.; Lucchi, N. W.; Grant, Q.; Udhayakumar, V.; Alexandre, J. S.; Demar, M.; Ringwald, P.; Neafsey, D. E.; Fidock, D. A.; Musset, L. Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance, eLife, Volume 9 (2020) | DOI

[19] Menard, D.; Dondorp, A. Antimalarial Drug Resistance: A Threat to Malaria Elimination, Cold Spring Harbor Perspectives in Medicine, Volume 7 (2017) no. 7 | DOI

[20] Mok, S.; Ashley, E. A.; Ferreira, P. E.; Zhu, L.; Lin, Z.; Yeo, T.; Chotivanich, K.; Imwong, M.; Pukrittayakamee, S.; Dhorda, M.; Nguon, C.; Lim, P.; Amaratunga, C.; Suon, S.; Hien, T. T.; Htut, Y.; Faiz, M. A.; Onyamboko, M. A.; Mayxay, M.; Newton, P. N.; Tripura, R.; Woodrow, C. J.; Miotto, O.; Kwiatkowski, D. P.; Nosten, F.; Day, N. P. J.; Preiser, P. R.; White, N. J.; Dondorp, A. M.; Fairhurst, R. M.; Bozdech, Z. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance, Science, Volume 347 (2015) no. 6220, pp. 431-435 | DOI

[21] Nair, S.; Li, X.; Arya, G. A.; McDew-White, M.; Ferrari, M.; Nosten, F.; Anderson, T. J. C. Fitness Costs and the Rapid Spread of kelch13-C580Y Substitutions Conferring Artemisinin Resistance, Antimicrobial Agents and Chemotherapy, Volume 62 (2018) no. 9 | DOI

[22] O’Neill, P. M.; Barton, V. E.; Ward, S. A. The Molecular Mechanism of Action of Artemisinin—The Debate Continues, Molecules, Volume 15 (2010) no. 3, pp. 1705-1721 | DOI

[23] Ord, R.; Alexander, N.; Dunyo, S.; Hallett, R.; Jawara, M.; Targett, G.; Drakeley, C. J.; Sutherland, C. J. Seasonal Carriage of pfcrt and pfmdr1 Alleles in Gambian Plasmodium falciparum Imply Reduced Fitness of Chloroquine‐Resistant Parasites, The Journal of Infectious Diseases, Volume 196 (2007) no. 11, pp. 1613-1619 | DOI

[24] Pollitt, L. C.; Huijben, S.; Sim, D. G.; Salathé, R. M.; Jones, M. J.; Read, A. F. Rapid Response to Selection, Competitive Release and Increased Transmission Potential of Artesunate-Selected Plasmodium chabaudi Malaria Parasites, PLoS Pathogens, Volume 10 (2014) no. 4 | DOI

[25] Read, A. F.; Huijben, S. Evolutionary biology and the avoidance of antimicrobial resistance, Evolutionary Applications, Volume 2 (2009) no. 1, pp. 40-51 | DOI

[26] Rivero, A.; Gandon, S. Evolutionary Ecology of Avian Malaria: Past to Present, Trends in Parasitology, Volume 34 (2018) no. 8, pp. 712-726 | DOI

[27] Sirawaraporn, W.; Sathitkul, T.; Sirawaraporn, R.; Yuthavong, Y.; Santi, D. V. Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase, Proceedings of the National Academy of Sciences, Volume 94 (1997) no. 4, pp. 1124-1129 | DOI

[28] St. Laurent, B.; Miller, B.; Burton, T. A.; Amaratunga, C.; Men, S.; Sovannaroth, S.; Fay, M. P.; Miotto, O.; Gwadz, R. W.; Anderson, J. M.; Fairhurst, R. M. Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa, Nature Communications, Volume 6 (2015) no. 1 | DOI

[29] Straimer, J.; Gnädig, N. F.; Witkowski, B.; Amaratunga, C.; Duru, V.; Ramadani, A. P.; Dacheux, M.; Khim, N.; Zhang, L.; Lam, S.; Gregory, P. D.; Urnov, F. D.; Mercereau-Puijalon, O.; Benoit-Vical, F.; Fairhurst, R. M.; Ménard, D.; Fidock, D. A. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates, Science, Volume 347 (2014) no. 6220, pp. 428-431 | DOI

[30] Tirrell, A. R.; Vendrely, K. M.; Checkley, L. A.; Davis, S. Z.; McDew-White, M.; Cheeseman, I. H.; Vaughan, A. M.; Nosten, F. H.; Anderson, T. J. C.; Ferdig, M. T. Pairwise growth competitions identify relative fitness relationships among artemisinin resistant Plasmodium falciparum field isolates, Malaria Journal, Volume 18 (2019) no. 1 | DOI

[31] Uhlemann, A.-C.; Fidock, D. A. Loss of malarial susceptibility to artemisinin in Thailand, The Lancet, Volume 379 (2012) no. 9830, pp. 1928-1930 | DOI

[32] Uwimana, A.; Legrand, E.; Stokes, B. H.; Ndikumana, J.-L. M.; Warsame, M.; Umulisa, N.; Ngamije, D.; Munyaneza, T.; Mazarati, J.-B.; Munguti, K.; Campagne, P.; Criscuolo, A.; Ariey, F.; Murindahabi, M.; Ringwald, P.; Fidock, D. A.; Mbituyumuremyi, A.; Menard, D. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda, Nature Medicine, Volume 26 (2020) no. 10, pp. 1602-1608 | DOI

[33] Walliker, D.; Hunt, P.; Babiker, H. Fitness of drug-resistant malaria parasites, Acta Tropica, Volume 94 (2005) no. 3, pp. 251-259 | DOI

[34] Wargo, A. R.; Huijben, S.; de Roode, J. C.; Shepherd, J.; Read, A. F. Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model, Proceedings of the National Academy of Sciences, Volume 104 (2007) no. 50, pp. 19914-19919 | DOI

[35] World Health Organization World Malaria Report 2021, Geneva, 2021

[36] Witkowski, B.; Khim, N.; Chim, P.; Kim, S.; Ke, S.; Kloeung, N.; Chy, S.; Duong, S.; Leang, R.; Ringwald, P.; Dondorp, A. M.; Tripura, R.; Benoit-Vical, F.; Berry, A.; Gorgette, O.; Ariey, F.; Barale, J.-C.; Mercereau-Puijalon, O.; Menard, D. Reduced Artemisinin Susceptibility of Plasmodium falciparum Ring Stages in Western Cambodia, Antimicrobial Agents and Chemotherapy, Volume 57 (2013) no. 2, pp. 914-923 | DOI

[37] Zélé, F.; Nicot, A.; Berthomieu, A.; Weill, M.; Duron, O.; Rivero, A. Wolbachia increases susceptibility to Plasmodium infection in a natural system, Proceedings of the Royal Society B: Biological Sciences, Volume 281 (2014) no. 1779 | DOI

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