ArticleMicrobiology spectrum2022
The Knock-Down of the Chloroquine Resistance Transporter PfCRT Is Linked to Oligopeptide Handling in Plasmodium falciparum.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- PfATG18 links V-ATPase assembly to endocytic membrane dynamics in malaria parasites.PLoS pathogens · 2026Article
- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- Gain-of-function PfAAT1 mutations compensate for impaired PfCRT function inResearch square · 2026Article
- Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum.Nature communications · 2026Article
- The impact of Iso-mukaadial acetate on Plasmodium falciparum transcriptional gene regulation.Scientific reports · 2025Article
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
- Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance Are Infrequent and Impart a Major Fitness Cost.The Journal of infectious diseases · 2025Article
- Identification of a large anion channel required for digestive vacuole acidification and amino acid export in Plasmodium falciparum.PLoS biology · 2025Article
- Deletion of theAntimicrobial agents and chemotherapy · 2025Article
- Molecular basis of the functional conflict between chloroquine and peptide transport in the Malaria parasite chloroquine resistance transporter PfCRT.Nature communications · 2025Article
- Identification of Malaria-Selective Proteasome β5 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation.International journal of molecular sciences · 2024Article
- A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.PLoS pathogens · 2024Article
- Antimalarial Activity of Aqueous Extracts of Nasturtium (Molecules (Basel, Switzerland) · 2024Article
- Transforming the CRISPR/dCas9-based gene regulation technique into a forward screening tool iniScience · 2024Article
- Novel quinolinepiperazinyl-aryltetrazoles targeting the blood stage ofRSC medicinal chemistry · 2024Article
- Article
- Mapping the genomic landscape of multidrug resistance inScience advances · 2023Article
- pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.Nature communications · 2023Article
- PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport.PLoS pathogens · 2023Article
- Structures ofBiochemistry · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chloroquine resistance transporter, PfCRT, is an essential factor during intraerythrocytic development of the human malaria parasite Plasmodium falciparum. PfCRT resides at the digestive vacuole of the parasite, where hemoglobin taken up by the parasite from its host cell is degraded. PfCRT can acquire several mutations that render PfCRT a drug transporting system expelling compounds targeting hemoglobin degradation from the digestive vacuole. The non-drug related function of PfCRT is less clear, although a recent study has suggested a role in oligopeptide transport based on studies conducted in a heterologous expression system. The uncertainty about the natural function of PfCRT is partly due to a lack of a null mutant and a dearth of functional assays in the parasite. Here, we report on the generation of a conditional PfCRT knock-down mutant in P. falciparum. The mutant accumulated oligopeptides 2 to at least 8 residues in length under knock-down conditions, as shown by comparative global metabolomics. The accumulated oligopeptides were structurally diverse, had an isoelectric point between 4.0 and 5.4 and were electrically neutral or carried a single charge at the digestive vacuolar pH of 5.2. Fluorescently labeled dipeptides and live cell imaging identified the digestive vacuole as the compartment where oligopeptides accumulated. Our findings suggest a function of PfCRT in oligopeptide transport across the digestive vacuolar membrane in P. falciparum and associated with it a role in nutrient acquisition and the maintenance of the colloid osmotic balance.
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