ArticlePloS one2013
A process similar to autophagy is associated with cytocidal chloroquine resistance in Plasmodium falciparum.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Isolation and characterization ofAntimicrobial agents and chemotherapy · 2025Article
- Cytoprotective autophagy as a pro-survival strategy in ART-resistant malaria parasites.Cell death discovery · 2023Article
- Structures ofBiochemistry · 2023Article
- An Alternative Autophagy-Related Mechanism of Chloroquine Drug Resistance in the Malaria Parasite.Antimicrobial agents and chemotherapy · 2022Article
- Artemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification Pathway.Antimicrobial agents and chemotherapy · 2021Article
- Autophagy in the control and pathogenesis of parasitic infections.Cell & bioscience · 2020Review
- Artemisinin-Based Antimalarial Drug Therapy: Molecular Pharmacology and Evolving Resistance.Tropical medicine and infectious disease · 2019Review
- Structural Analysis ofFrontiers in bioengineering and biotechnology · 2019Article
- Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites.Scientific reports · 2018Article
- Article
- Apicomplexan autophagy and modulation of autophagy in parasite-infected host cells.Biomedical journal · 2017Review
- Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border.Scientific reports · 2016Article
- Article
- Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.Malaria journal · 2016Article
- High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations.Scientific reports · 2015Article
- Functional Comparison of 45 Naturally Occurring Isoforms of the Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT).Biochemistry · 2015Article
- Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter.Molecular microbiology · 2015Article
- Determination of the cytostatic and cytocidal activities of antimalarial compounds and their combination interactions.Current protocols in chemical biology · 2014Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ LD50. Candidate genes in these loci are consistent with a role for autophagy in CQR(CC), leading us to directly examine the autophagy pathway in intraerythrocytic CQR parasites. Indirect immunofluorescence of RBC infected with synchronized CQS vs CQR trophozoite stage parasites reveals differences in the distribution of the autophagy marker protein PfATG8 coinciding with CQR(CC). Taken together, the data show that an unusual autophagy-like process is either activated or inhibited for intraerythrocytic trophozoite parasites at LD50 doses (but not IC50 doses) of CQ, that the pathway is altered in CQR P. falciparum, and that it may contribute along with mutations in PfCRT to confer the CQR(CC) phenotype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.