Journal article
Complex inheritance of the plasmodial surface anion channel in a Plasmodium falciparum genetic cross
Molecular microbiology, v 72(2), pp 459-469
Apr 2009
PMID: 19320831
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human erythrocytes infected with the malaria parasite
P. falciparum
have increased permeabilities to many solutes. The plasmodial surface anion channel (PSAC) may mediate these changes. Despite good understanding of the biochemical and biophysical properties, the genetic basis of PSAC activity remains unknown. Functional polymorphisms in laboratory isolates and two mutants generated by
in vitro
selection implicate a parasite-encoded channel, though parasite-induced modifications of endogenous channels have not been formally excluded. Here, we identified stable differences in furosemide efficacy against PSAC activity induced by HB3 and 3D7A parasites. This difference was apparent in both single PSAC patch-clamp recordings and in sorbitol-mediated osmotic lysis measurements, confirming that Cl
−
and sorbitol are transported by a single channel type. Examination of 19 progeny from a genetic cross between HB3 and 3D7A revealed complex inheritance with some cloned progeny exhibiting furosemide affinities outside the range of parental values. Isolates generated by selfing of the 3D7A clone also exhibited altered furosemide affinities, implicating changes in one or more alleles during meiosis or passage through a primate host. PSAC may be encoded by multiple parasite genes (e.g. a multi-gene family or multiple genes that encode distinct channel subunits) or a single polymorphic gene under strong selective pressure.
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Details
- Title
- Complex inheritance of the plasmodial surface anion channel in a Plasmodium falciparum genetic cross
- Creators
- Abdulnaser Alkhalil - The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852Ajay D Pillai - The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852Abdullah A.B Bokhari - The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852Akhil B Vaidya - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Sanjay A Desai - The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852
- Publication Details
- Molecular microbiology, v 72(2), pp 459-469
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000265014500016
- Scopus ID
- 2-s2.0-64149119179
- Other Identifier
- 991014877679404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Microbiology