Some mutations that enable drug resistance in the malaria-causing parasite Plasmodium falciparum may also help it grow, according to a new study published in PLOS Pathogens.
P. falciparum is a single-celled parasite that infects the human bloodstream and causes the most severe form of malaria. Some strains of P. falciparum have evolved resistance to antimalarial drugs, including the commonly used drug chloroquine. Often, chloroquine resistance mutations hinder P. falciparum's ability to infect the bloodstream and grow.
However, in a previous study, researchers discovered that a uniquely mutated version of the P. falciparum gene known as pfcrt provides drug resistance while avoiding the detrimental impact of growth seen with more widely distributed mutated pfcrt variants.
In the new study, the team investigated this version, or allele, of the pfcrt gene, which is called Cam734 and has been found in certain regions in Southeast Asia. Using DNA-modifying proteins called zinc-finger nucleases, they characterized the individual mutations unique to Cam734 in terms of their effects on drug resistance, metabolism, and growth rates in living parasites.
The researchers found that a mutation called A144F is required for the chloroquine resistance enabled by Cam734 and that this mutation also contributes to resistance to first-line drugs amodiaquine and quinine. Additional mutations were identified that contributed to resistance to chloroquine and impacted the potency of other antimalarials. When the scientists reversed these mutations in living parasites that had the Cam734 allele, growth slowed, indicating that these mutations also enhance infection.
Additional experiments identified specific effects of Cam734 mutations on several metabolic pathways in P. falciparum, including the digestion of human hemoglobin that parasites use to obtain amino acids for protein synthesis.
They also found evidence that Cam734 helps to maintain an electrochemical gradient that allows the protein encoded by the pfcrt gene to thwart the cellular effects of chloroquine.
These new findings significantly broaden scientists' understanding of Cam734, the second most common variant of the pfcrt gene in Southeast Asia. The findings identify multiple intracellular processes and multidrug resistance phenotypes impacted by changes in PfCRT and can help inform future malaria treatment efforts.
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005976
Drug resistance mutations also enhance growth in malaria parasite
- 1,586 views
- Added
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Single brain region links depression and anxiety, heart disease, an…
Read more
Why are some COVID-19 infected people asymptomatic?
Read more
How a common mutation leads to sleep disorder
Read more
Brainstem neuronal gene expression controls both behaviour and misb…
Read more
How the brain manages to adapt without a corpus callosum
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar