1. Home ›
  2. Research

Parasite Fitness

A grid of line graphs shows the competitive growth of *Plasmodium falciparum* strains. Each graph plots the ratio of a specific strain over time, measured in days. The strains are labeled with NHP followed by a number and a mutation code if applicable. The graph demonstrates how different strains, both wild-type and mutant, compete and grow over time in various combinations. Each row represents a distinct initial strain pairing, while each column compares one of these strains against others, including NF54 (wild-type) as a control. Different colors are used to represent distinct *P. falciparum* strains.

The fitness of a parasite is strongly associated with its ability to spread in a population in the absence of external selective pressures. However, acquisition of resistance conferring mutations has also been found to come with a cost to parasite fitness. To compensate for this fitness cost, additional genetic modifications can restore the fitness-resistance balance, allowing multidrug resistant parasite lineages to spread.

 

Little is understood about the determinants of malaria parasite fitness outside of the blood stage, due to the difficulty in studying the obligate mosquito stages essential for parasite transmission as well as the crucial liver stage of the life cycle. Further, it is not known if mutations associated with drug resistance affect other stages of the life cycle and the evolutionary consequences of this. Fitness advantages of drug-resistant parasites during the pre- erythrocytic phase of infection could lead to faster spread of resistance mutations.

Publications

Tirrell AR, Vendrely KM, Checkley LA, Davis SZ, McDew-White M, Cheeseman IH, Vaughan AM, Nosten FH, Anderson TJC, Ferdig MT. Pairwise growth competitions identify relative fitness relationships among artemisinin resistant Plasmodium falciparum field isolates. Malar J. 2019 Aug 28;18(1):295. doi: 10.1186/s12936-019-2934-4. PMID: 31462253; PMCID: PMC6714446.

Li X, Kumar S, McDew-White M, Haile M, Cheeseman IH, et al. (2019) Genetic mapping of fitness determinants across the malaria parasite Plasmodium falciparum life cycle. PLOS Genetics 15(10): e1008453. https://doi.org/10.1371/journal.pgen.1008453

Amambua-Ngwa A, Button-Simons KA, Li X, Kumar S, Brenneman KV, Ferrari M, Checkley LA, Haile MT, Shoue DA, McDew-White M, Tindall SM, Reyes A, Delgado E, Dalhoff H, Larbalestier JK, Amato R, Pearson RD, Taylor AB, Nosten FH, D'Alessandro U, Kwiatkowski D, Cheeseman IH, Kappe SHI, Avery SV, Conway DJ, Vaughan AM, Ferdig MT, Anderson TJC. Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1. Nat Microbiol. 2023 Jul;8(7):1213-1226. doi: 10.1038/s41564-023-01377-z. Epub 2023 May 11. PMID: 37169919; PMCID: PMC10322710.

Kane J, Li X, Kumar S, Button-Simons KA, Vendrely Brenneman KM, Dahlhoff H, Sievert MAC, Checkley LA, Shoue DA, Singh PP, Abatiyow BA, Haile MT, Nair S, Reyes A, Tripura R, Peto TJ, Lek D, Mukherjee A,Kappe SHI, Dhorda M, Nkhoma SC, Cheeseman IH,Vaughan AM, Anderson TJC, Ferdig MT.2024. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance. mBio15:e00805-24. https://doi.org/10.1128/mbio.00805-24