ArticleBMC genomics2018
Altered expression of K13 disrupts DNA replication and repair in Plasmodium falciparum.
Article in BMC genomics, 2018. 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.
- Russian Dolls of Heme Metabolism in Malaria-Infected Red Blood Cells: Nested Vulnerabilities and Therapeutic Opportunities.Pathogens (Basel, Switzerland) · 2026Review
- Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.Nature communications · 2024Article
- Unraveling the complexities of ApiAP2 regulation in Plasmodium falciparum.Trends in parasitology · 2024Review
- Epidemiology, Detection and Treatment of Malaria.Tropical medicine and infectious disease · 2024Article
- Impact of different mutations on Kelch13 protein levels, ART resistance, and fitness cost inmBio · 2024Article
- Article
- What exactly does the PfK13 C580Y mutation in Plasmodium falciparum influence?Parasites & vectors · 2023Article
- MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites.Genome biology · 2023Article
- A novel Modulator of Ring Stage Translation (MRST) gene alters artemisinin sensitivity inmSphere · 2023Article
- Chemogenomic Profiling of a Plasmodium falciparum Transposon Mutant Library Reveals Shared Effects of Dihydroartemisinin and Bortezomib on Lipid Metabolism and Exported Proteins.Microbiology spectrum · 2023Article
- Structural Modelling Prediction of RecombinantPathogens (Basel, Switzerland) · 2022Article
- Naturally Acquired Kelch13 Mutations in Plasmodium falciparum Strains ModulateMicrobiology spectrum · 2022Article
- Label-free quantitative proteomic analysis of ethanamizuril-resistant versus -sensitive strains of Eimeria tenella.Parasites & vectors · 2022Article
- Article
- Transcriptome-module phenotype association study implicates extracellular vesicles biogenesis inFrontiers in cellular and infection microbiology · 2022Article
- Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2021Article
- The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.Nature communications · 2021Article
- Essential Genes of the Parasitic Apicomplexa.Trends in parasitology · 2021Review
- Molecular Mechanisms of Drug Resistance inAnnual review of microbiology · 2020Review
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10 authors.
Funding
Abstract
backgroundPlasmodium falciparum exhibits resistance to the artemisinin component of the frontline antimalarial treatment Artemisinin-based Combination Therapy in South East Asia. Millions of lives will be at risk if artemisinin resistance (ART-R) spreads to Africa. Single non-synonymous mutations in the propeller region of PF3D7_1343700,"K13" are implicated in resistance. In this work, we use transcriptional profiling to characterize a laboratory-generated k13 insertional mutant previously demonstrated to have increased sensitivity to artemisinins to explore the functional role of k13.
resultsA set of RNA-seq and microarray experiments confirmed that the expression profile of k13 is specifically altered during the early ring and early trophozoite stages of the mutant intraerythrocytic development cycle. The down-regulation of k13 transcripts in this mutant during the early ring stage is associated with a transcriptome advance towards a more trophozoite-like state. To discover the specific downstream effect of k13 dysregulation, we developed a new computational method to search for differential gene expression while accounting for the temporal sequence of transcription. We found that the strongest biological signature of the transcriptome shift is an up-regulation of DNA replication and repair genes during the early ring developmental stage and a down-regulation of DNA replication and repair genes during the early trophozoite stage; by contrast, the expressions of housekeeping genes are unchanged. This effect, due to k13 dysregulation, is antagonistic, such that k13 levels are negatively correlated with DNA replication and repair gene expression.
conclusionOur results support a role for k13 as a stress response regulator consistent with the hypothesis that artemisinins mode of action is oxidative stress and k13 as a functional homolog of Keap1 which in humans regulates DNA replication and repair genes in response to oxidative stress.
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