Publication: Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine
Accepted Date
2011-08-18
Issued Date
2011-08-18
Copyright Date
2011
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Language
eng
ISSN
1475-2875 (electronic)
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Mahidol University
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BioMed Central
Bibliographic Citation
Kritsiriwuthinan K, Chaotheing S, Shaw PJ, Wongsombat C, Chavalitshewinkoon-Petmitr P, Kamchonwongpaisan S. Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine. Malar J. 2011 Aug 18;10:242.
Suggested Citation
Kanyanan Kritsiriwuthinan, กัญญนันทน์ กฤษศิริวุฒินันท์, Sastra Chaotheing, Shaw, Philip J., Chayaphat Wongsombat, Porntip Chavalitshewinkoon-Petmitr, พรทิพย์ เพ็ชรมิตร, Sumalee Kamchonwongpaisan, สุมาลี กำจรวงศ์ไพศาล Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine. Kritsiriwuthinan K, Chaotheing S, Shaw PJ, Wongsombat C, Chavalitshewinkoon-Petmitr P, Kamchonwongpaisan S. Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine. Malar J. 2011 Aug 18;10:242.. doi:10.1186/1475-2875-10-242 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/730
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Title
Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine
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Abstract
BACKGROUND: Pyronaridine (PN) and chloroquine (CQ) are structurally related
anti-malarial drugs with primarily the same mode of action. However, PN is
effective against several multidrug-resistant lines of Plasmodium falciparum,
including CQ resistant lines, suggestive of important operational differences
between the two drugs.
METHODS: Synchronized trophozoite stage cultures of P. falciparum strain K1 (CQ
resistant) were exposed to 50% inhibitory concentrations (IC50) of PN and CQ, and
parasites were harvested from culture after 4 and 24 hours exposure. Global
transcriptional changes effected by drug treatment were investigated using DNA
microarrays.
RESULTS: After a 4 h drug exposure, PN induced a greater degree of
transcriptional perturbation (61 differentially expressed features) than CQ (10
features). More genes were found to respond to 24 h treatments with both drugs,
and 461 features were found to be significantly responsive to one or both drugs
across all treatment conditions. Filtering was employed to remove features
unrelated to primary drug action, specifically features representing genes
developmentally regulated, secondary stress/death related processes and sexual
stage development. The only significant gene ontologies represented among the 46
remaining features after filtering relate to host exported proteins from
multi-gene families.
CONCLUSIONS: The malaria parasite's molecular responses to PN and CQ treatment
are similar in terms of the genes and pathways affected. However, PN appears to
exert a more rapid response than CQ. The faster action of PN may explain why PN
is more efficacious than CQ, particularly against CQ resistant isolates. In
agreement with several other microarray studies of drug action on the parasite,
it is not possible, however, to discern mechanism of drug action from the
drug-responsive genes.