ArticleDNA research : an international journal for rapid publication of reports on genes and genomes2014
Generation of rodent malaria parasites with a high mutation rate by destructing proofreading activity of DNA polymerase δ.
Article in DNA research : an international journal for rapid publication of reports on genes and genomes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Article
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- X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease.Experimental neurology · 2023Review
- Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum.Nature communications · 2023Article
- Analysis of genome instability and implications for the consequent phenotype inMicrobial genomics · 2023Article
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
- The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Traffic (Copenhagen, Denmark) · 2022Article
- A differential equation, deduced from a DNA-type genetic algorithm with the lagging-strand-biased mutagenesis.Heliyon · 2022Article
- Isolation of Mutants With Reduced Susceptibility to Piperaquine From a Mutator of the Rodent Malaria ParasiteFrontiers in cellular and infection microbiology · 2021Article
- The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites.Cell chemical biology · 2020Article
- Draft Genome Sequence ofGenome announcements · 2017Article
- Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ.Scientific reports · 2016Article
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Authors and funding
16 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum malaria imposes a serious public health concern throughout the tropics. Although genetic tools are principally important to fully investigate malaria parasites, currently available forward and reverse tools are fairly limited. It is expected that parasites with a high mutation rate can readily acquire novel phenotypes/traits; however, they remain an untapped tool for malaria biology. Here, we generated a mutator malaria parasite (hereinafter called a 'malaria mutator'), using site-directed mutagenesis and gene transfection techniques. A mutator Plasmodium berghei line with a defective proofreading 3' → 5' exonuclease activity in DNA polymerase δ (referred to as PbMut) and a control P. berghei line with wild-type DNA polymerase δ (referred to as PbCtl) were maintained by weekly passage in ddY mice for 122 weeks. High-throughput genome sequencing analysis revealed that two PbMut lines had 175-178 mutations and a 86- to 90-fold higher mutation rate than that of a PbCtl line. PbMut, PbCtl, and their parent strain, PbWT, showed similar course of infection. Interestingly, PbMut lost the ability to form gametocytes during serial passages. We believe that the malaria mutator system could provide a novel and useful tool to investigate malaria biology.
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