Evidence map›Paper›PMID 22792308›Full record

ArticlePloS one2012

Functional analysis of Plasmodium vivax dihydrofolate reductase-thymidylate synthase genes through stable transformation of Plasmodium falciparum.

Alyson M Auliff, Bharath Balu, Nanhua Chen, Michael T O'Neil, Qin Cheng, John H Adams

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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 3 institutions in 2 countries.

Alyson M AuliffDrug Resistance and Diagnostics Department, Australian Army Malaria Institute, Enoggera, Queensland, Australia.
Bharath Balu
Nanhua Chen
Michael T O'Neil
Qin Cheng
John H Adams
University of Queensland · AUUniversity of South Florida · USWalter Reed Army Institute of Research · US

Funding

MOLECULAR ANALYSIS OF APICAL ORGANELLES OF PLASMODIUMR01AI033656 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI ADAMS, JOHN H · 2000 to 2009
$2.9M
A large-scale transposon mutagenesis screen of Plasmodium falciparumR01AI094973 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI ADAMS, JOHN H · 2011 to 2015
$1.8M
Developing a Transposon-based Toolkit for Genetic Analysis of Malaria ParasitesR21AI070888 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI ADAMS, JOHN · 2006 to 2007
$372k
NIAID NIH HHS R01 AI033656NIAID NIH HHS R01AI033656NIAID NIH HHS R01 AI094973NIAID NIH HHS R21 AI070888NIAID NIH HHS R21AI070888
6 · The paper itself

Abstract

Mechanisms of drug resistance in Plasmodium vivax have been difficult to study partially because of the difficulties in culturing the parasite in vitro. This hampers monitoring drug resistance and research to develop or evaluate new drugs. There is an urgent need for a novel method to study mechanisms of P. vivax drug resistance. In this paper we report the development and application of the first Plasmodium falciparum expression system to stably express P. vivax dhfr-ts alleles. We used the piggyBac transposition system for the rapid integration of wild-type, single mutant (117N) and quadruple mutant (57L/58R/61M/117T) pvdhfr-ts alleles into the P. falciparum genome. The majority (81%) of the integrations occurred in non-coding regions of the genome; however, the levels of pvdhfr transcription driven by the P. falciparum dhfr promoter were not different between integrants of non-coding and coding regions. The integrated quadruple pvdhfr mutant allele was much less susceptible to antifolates than the wild-type and single mutant pvdhfr alleles. The resistance phenotype was stable without drug pressure. All the integrated clones were susceptible to the novel antifolate JPC-2067. Therefore, the piggyBac expression system provides a novel and important tool to investigate drug resistance mechanisms and gene functions in P. vivax.

Indexed as

Amino Acid SubstitutionAntimalarialsCells, CulturedDrug ResistanceErythrocytesFolic Acid AntagonistsGene DosageHumansInhibitory Concentration 50Mutagenesis, InsertionalPlasmodium falciparumPlasmodium vivaxProguanilProtozoan ProteinsPyrimethamineRecombinant Proteins4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-(2-chloro-4-trifluoromethoxyphenoxy)propyloxy)-1,3,5-triazineAntimalarialsBRL 6231clociguanilcycloguanilFolic Acid AntagonistsProguanilProtozoan ProteinsPyrimethamineRecombinant ProteinsTetrahydrofolate DehydrogenaseThymidylate SynthaseTriazines

Identifiers

PMID22792308
PMCPMC3392216
OpenAlexW2040455050

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.