ArticleMolecular and biochemical parasitology2007
The role of DNA mismatch repair in generating genetic diversity and drug resistance in malaria parasites.
Article in Molecular and biochemical parasitology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 26 citations in OpenAlex.
- Evolutionary Rate Covariation Across Malaria Parasite Species Enables Inference of Protein Interactions.Genome biology and evolution · 2026Article
- Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?Malaria journal · 2026Review
- Evolutionary rate covariation across malaria parasite species enables inference of protein interactions.bioRxiv : the preprint server for biology · 2026Article
- Analysis of genome instability and implications for the consequent phenotype inMicrobial genomics · 2023Article
- Mutators Enhance Adaptive Micro-Evolution in Pathogenic Microbes.Microorganisms · 2022Review
- An SR protein is essential for activating DNA repair in malaria parasites.Journal of cell science · 2021Article
- Article
- Genome-wide microsatellite characteristics of five human Plasmodium species, focusing on Plasmodium malariae and P. ovale curtisi.Parasite (Paris, France) · 2020Article
- ATPase activity of Plasmodium falciparum MLH is inhibited by DNA-interacting ligands and dsRNAs of MLH along with UvrD curtail malaria parasite growth.Protoplasma · 2017Article
- Genome WideFrontiers in microbiology · 2017Article
- Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity.Nucleic acids research · 2014Article
- Higher microsatellite diversity in Plasmodium vivax than in sympatric Plasmodium falciparum populations in Pursat, Western Cambodia.Experimental parasitology · 2013Article
- Antigenic variation and the generation of diversity in malaria parasites.Current opinion in microbiology · 2012Review
- Malaria drug resistance is associated with defective DNA mismatch repair.Molecular and biochemical parasitology · 2011Article
- Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response.Molecular and biochemical parasitology · 2011Article
- Variable numbers of tandem repeats in Plasmodium falciparum genes.Journal of molecular evolution · 2010Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although the mechanisms by which malaria parasites develop resistance to drugs are unclear, current knowledge suggests a main mechanism of resistance is the alteration of target enzymes by point mutation. In other organisms, defects in DNA mismatch repair have been linked to increased mutation rates and drug resistance. We have identified an unusual complement of mismatch repair genes in the Plasmodium genome. An initial functional test of two of these genes (PfMSH2-1 and PfMSH2-2) using a dominant mutator assay showed an elevation in mutation frequency with the PfMSH2-2 homolog, indirectly demonstrating a role for this gene in mismatch repair. We successfully disrupted PbMSH2-2 in the Plasmodium berghei laboratory isolate NK65, and showed that this gene is not essential for parasite growth in either the asexual (rodent) or sexual (mosquito) stages of the lifecycle. Although we observed some differences in levels of drug resistance between wild type and mutant parasites, no uniform trend emerged and preliminary evidence does not support a strong link between PbMSH2-2 disruption and dramatically increased drug resistance. We found microsatellite polymorphism in the PbMSH2-2 disrupted parasites in less than 40 life cycles post-transfection, but not in PbMap2K disrupted controls or mosquito-passaged wild type parasites, which suggests a possible role for PbMSH2-2 in preventing microsatellite slippage, similar to MSH2 in other organisms. Our studies suggest that Plasmodium species may have evolved a unique variation on the highly conserved system of DNA repair compared to the mismatch repair systems in other eukaryotes.
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