Sulfadoxine-pyrimethamine resistance in the rodent malaria parasite Plasmodium chabaudi

Hayton, K., Ranford-Cartwright, L. and Walliker, D. (2002) Sulfadoxine-pyrimethamine resistance in the rodent malaria parasite Plasmodium chabaudi. Antimicrobial Agents and Chemotherapy, 46(8), pp. 2482-2489. (doi: 10.1128/AAC.46.8.2482-2489.2002) (PMID:12121922) (PMCID:PMC127344)

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Abstract

We have studied resistance to sulfadoxine-pyrimethamine (S/P) in the rodent malaria parasite Plasmodium chabaudi. A stable S/P-resistant mutant, AS(50S/P), was selected by drug treatment of a clone, AS(PYR), already resistant to pyrimethamine. The sequences of the P. chabaudi dhfr and dhps genes were obtained and found to be identical in AS(50S/P) and AS(PYR), showing that resistance to S/P in AS(50S/P) was not due to additional mutations in either gene. AS(50S/P) was crossed with a drug-sensitive clone, AJ, and 16 independent recombinant progeny were obtained. These clones were phenotyped for their susceptibility to S/P and to sulfadoxine and pyrimethamine separately. Pyrimethamine resistance was invariably associated with S/P resistance, but no correlation was found between resistance to S/P and resistance to sulfadoxine. Quantitative trait locus analysis of the progeny with 31 chromosome-specific markers showed that mutant P. chabaudi dhfr, or one or more genes closely linked to it, was a major determinant of S/P resistance. In addition, the inheritance of genes on chromosomes 5 and 13 from the sensitive parent appeared to contribute to the level of resistance observed. These results demonstrate that the S/P resistance of the AS(50S/P) mutant of P. chabaudi does not involve mutation in dhps and is not due simply to a combination of two genes determining resistance to pyrimethamine and sulfadoxine separately.

Item Type:Articles
Additional Information:A correction to this article is available at https://doi.org/10.1128/aac.48.8.3215.2004.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ranford-Cartwright, Dr Lisa
Authors: Hayton, K., Ranford-Cartwright, L., and Walliker, D.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Antimicrobial Agents and Chemotherapy
Journal Abbr.:Antimicrob Agents Chemother
Publisher:American Society for Microbiology
ISSN:0066-4804
ISSN (Online):1098-6596
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