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Sequence and gene expression of chloroquine resistance transporter (pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum.

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Chaijaroenkul, Wanna, Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192, Mungthin, Mathirut, Johnson, David, Owen, Andrew, Bray, Patrick and Na-Bangchang, Kesara (2011) 'Sequence and gene expression of chloroquine resistance transporter (pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum.'. Malaria Journal, Vol 10, Issue 1, p. 42.

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Abstract

Background
Plasmodium falciparum chloroquine resistance (CQR) transporter protein (PfCRT) is known to be the important key of CQR. Recent studies have definitively demonstrated a link between mutations in the gene pfcrt and resistance to chloroquine in P. falciparum. Although these mutations are predictive of chloroquine resistance, they are not quantitatively predictive of the degree of resistance.

Methods
In this study, a total of 95 recently adapted P. falciparum isolates from Thailand were included in the analysis. Parasites were characterized for their drug susceptibility phenotypes and genotypes with respect to pfcrt. From the original 95 isolates, 20 were selected for complete pfcrt sequence analysis.

Results
Almost all of the parasites characterized carried the previously reported mutations K76T, A220S, Q271E, N326S, I356T and R371I. On complete sequencing, isolates were identified with novel mutations at K76A and E198K. There was a suggestion that parasites carrying E198K were less resistant than those that did not. In addition, pfcrt and pfmdr1 gene expression were investigated by real-time PCR. No relationship between the expression level of either of these genes and response to drug was observed.

Conclusion
Data from the present study suggest that other genes must contribute to the degree of resistance once the resistance phenotype is established through mutations in pfcrt.

Item Type: Article
Additional Information: The electronic version of this article is the complete one and can be found online at: http://www.malariajournal.com/content/10/1/42
Subjects: QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1186/1475-2875-10-42
Depositing User: Mary Creegan
Date Deposited: 03 Jun 2011 08:25
Last Modified: 06 Feb 2018 13:03
URI: https://archive.lstmed.ac.uk/id/eprint/2018

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