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Plasmodium falciparum
Image from CDC/Mae Melvin
Some mutations that enable drug resistance in the malaria parasite Plasmodium falciparum may also help it grow, according to a study published in PLOS Pathogens.
Some strains of P falciparum have evolved to become resistant to antimalarial drugs, including 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 pfcrt provides drug resistance while avoiding the detrimental impact of growth seen with other mutated pfcrt variants.
In the new study, the same group of researchers—Stanislaw Gabryszewski, of Columbia University Medical Center in New York, and his colleagues—investigated this version of the pfcrt gene, which is called Cam734 and has been found in certain regions in Southeast Asia.
Using zinc-finger nucleases, the team 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 this mutation also contributes to resistance to the drugs amodiaquine and quinine.
The team identified additional mutations that contribute to resistance to chloroquine and impact the potency of other antimalarials as well.
When the researchers reversed these mutations in living parasites that had the Cam734 allele, growth slowed, indicating that these mutations also enhance infection.
Additional experiments revealed 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.
The researchers also found evidence suggesting that Cam734 helps to maintain an electrochemical gradient that allows the protein encoded by the pfcrt gene to thwart the cellular effects of chloroquine.
The team said these findings broaden our 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. 
Plasmodium falciparum
Image from CDC/Mae Melvin
Some mutations that enable drug resistance in the malaria parasite Plasmodium falciparum may also help it grow, according to a study published in PLOS Pathogens.
Some strains of P falciparum have evolved to become resistant to antimalarial drugs, including 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 pfcrt provides drug resistance while avoiding the detrimental impact of growth seen with other mutated pfcrt variants.
In the new study, the same group of researchers—Stanislaw Gabryszewski, of Columbia University Medical Center in New York, and his colleagues—investigated this version of the pfcrt gene, which is called Cam734 and has been found in certain regions in Southeast Asia.
Using zinc-finger nucleases, the team 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 this mutation also contributes to resistance to the drugs amodiaquine and quinine.
The team identified additional mutations that contribute to resistance to chloroquine and impact the potency of other antimalarials as well.
When the researchers reversed these mutations in living parasites that had the Cam734 allele, growth slowed, indicating that these mutations also enhance infection.
Additional experiments revealed 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.
The researchers also found evidence suggesting that Cam734 helps to maintain an electrochemical gradient that allows the protein encoded by the pfcrt gene to thwart the cellular effects of chloroquine.
The team said these findings broaden our 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.
Plasmodium falciparum
Image from CDC/Mae Melvin
Some mutations that enable drug resistance in the malaria parasite Plasmodium falciparum may also help it grow, according to a study published in PLOS Pathogens.
Some strains of P falciparum have evolved to become resistant to antimalarial drugs, including 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 pfcrt provides drug resistance while avoiding the detrimental impact of growth seen with other mutated pfcrt variants.
In the new study, the same group of researchers—Stanislaw Gabryszewski, of Columbia University Medical Center in New York, and his colleagues—investigated this version of the pfcrt gene, which is called Cam734 and has been found in certain regions in Southeast Asia.
Using zinc-finger nucleases, the team 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 this mutation also contributes to resistance to the drugs amodiaquine and quinine.
The team identified additional mutations that contribute to resistance to chloroquine and impact the potency of other antimalarials as well.
When the researchers reversed these mutations in living parasites that had the Cam734 allele, growth slowed, indicating that these mutations also enhance infection.
Additional experiments revealed 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.
The researchers also found evidence suggesting that Cam734 helps to maintain an electrochemical gradient that allows the protein encoded by the pfcrt gene to thwart the cellular effects of chloroquine.
The team said these findings broaden our 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.