Evidence map›Paper›PMID 17583362›Full record

ArticleMolecular and biochemical parasitology2007

The role of DNA mismatch repair in generating genetic diversity and drug resistance in malaria parasites.

Lara Bethke, Susan Thomas, Kerone Walker, Ronak Lakhia, Radha Rangarajan, Dyann Wirth

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 26% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 26 citations in OpenAlex.

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  10. Genome WideFrontiers in microbiology · 2017
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Lara BethkeDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, United States. lara.bethke@icr.ac.uk
Susan Thomas
Kerone Walker
Ronak Lakhia
Radha Rangarajan
Dyann Wirth
Harvard University · USHarvard University Press · US

Funding

GENETIC POLYMORPHISMS AND DIVERSITY IN MALARIAR01GM061351 · NIGMS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WIRTH, DYANN F · 2000 to 2007
$3.7M
Plasmodium Sporozoites Motility and Cell InvasionR01AI050689 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WIRTH, DYANN F · 2002 to 2006
$1.6M
NIAID NIH HHS R01 AI050689NIAID NIH HHS R01-AI050689-03NIGMS NIH HHS R01 GM061351NIGMS NIH HHS R01-GM061351
6 · The paper itself

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.

Indexed as

DNA Mismatch RepairGenetic VariationAnimalsDrug ResistanceMicrosatellite RepeatsMutationOrotic AcidParasitic Sensitivity TestsPlasmodium bergheiPlasmodium falciparumPolymorphism, GeneticProtozoan ProteinsRats5-fluoroorotic acidOrotic AcidProtozoan Proteins

Identifiers

PMID17583362
PMCPMC3683857
OpenAlexW2076161107

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.