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Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018), Scientific Reports
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- Artemisinin is the most rapidly effective drug for Plasmodium falciparum malaria treatment currently in clinical use. Emerging artemisinin-resistant parasites pose a great global health risk. At present, the level of artemisinin resistance is still relatively low with evidence pointing towards a trade-off between artemisinin resistance and fitness loss. Here we show that artemisinin-resistant P. falciparum isolates from Cambodia manifested fitness loss, showing fewer progenies during the intra-erythrocytic developmental cycle. The loss in fitness was exacerbated under the condition of low exogenous amino acid supply. The resistant parasites failed to undergo maturation, whereas their drug-sensitive counterparts were able to complete the erythrocytic cycle under conditions of amino acid deprivation. The artemisinin-resistant phenotype was not stable, and loss of the phenotype was associated with changes in the expression of a putative target, Exp1, a membrane glutathione transferase. Analysis of SNPs in haemoglobin processing genes revealed associations with parasite clearance times, suggesting changes in haemoglobin catabolism may contribute to artemisinin resistance. These findings on fitness and protein homeostasis could provide clues on how to contain emerging artemisinin-resistant parasites.
- Subjects :
- 0301 basic medicine
Genotype
Plasmodium falciparum
Drug Resistance
lcsh:Medicine
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Article
Antimalarials
03 medical and health sciences
0302 clinical medicine
parasitic diseases
medicine
Humans
Amino Acids
Malaria, Falciparum
Artemisinin
lcsh:Science
Gene
2. Zero hunger
Genetics
chemistry.chemical_classification
Multidisciplinary
biology
lcsh:R
medicine.disease
biology.organism_classification
Phenotype
Artemisinins
3. Good health
Amino acid
030104 developmental biology
chemistry
Starvation
lcsh:Q
Genetic Fitness
Cambodia
030217 neurology & neurosurgery
Malaria
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....6abd4a22d60d3ae2f0b9e33adc031a1f