Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum
Publication Date
May 26, 2016
Journal
PLOS Pathogens
Authors
Sudipta Das, Suyash Bhatanagar, Joanne M. Morrisey, Thomas M. Daly, et al
Volume
12
Issue
5
Pages
e1005647
DOI
https://dx.plos.org/10.1371/journal.ppat.1005647
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005647
Web of Science
000379344500037
Scopus
84973345447
Mendeley
http://www.mendeley.com/research/na-influx-induced-new-antimalarials-causes-rapid-alterations-cholesterol-content-morphology-plasmodi
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Mendeley | Further Information

{"title"=>"Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum", "type"=>"journal", "authors"=>[{"first_name"=>"Sudipta", "last_name"=>"Das", "scopus_author_id"=>"57188557643"}, {"first_name"=>"Suyash", "last_name"=>"Bhatanagar", "scopus_author_id"=>"57189591518"}, {"first_name"=>"Joanne M.", "last_name"=>"Morrisey", "scopus_author_id"=>"7003392953"}, {"first_name"=>"Thomas M.", "last_name"=>"Daly", "scopus_author_id"=>"7005411939"}, {"first_name"=>"James M.", "last_name"=>"Burns", "scopus_author_id"=>"35498834400"}, {"first_name"=>"Isabelle", "last_name"=>"Coppens", "scopus_author_id"=>"6604095394"}, {"first_name"=>"Akhil B.", "last_name"=>"Vaidya", "scopus_author_id"=>"7103078700"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"27227970", "doi"=>"10.1371/journal.ppat.1005647", "sgr"=>"84973345447", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "scopus"=>"2-s2.0-84973345447", "issn"=>"15537374", "pui"=>"610667685"}, "id"=>"fdddf09f-cb48-367a-82af-5ac686294ab7", "abstract"=>"Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2), glycosylphosphotidylinositol (GPI)-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble \"rhoptries\" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise.", "link"=>"http://www.mendeley.com/research/na-influx-induced-new-antimalarials-causes-rapid-alterations-cholesterol-content-morphology-plasmodi", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>6, "Student > Master"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>6, "Student > Master"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>12, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>1}

Scopus | Further Information

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