Plasmodium falciparum: effect of anti-malarial drugs on the production and secretion characteristics of histidine-rich protein II.
Plasmodium falciparum histidine-rich protein II (HRP2) is one of the best documented malaria proteins. However, little is known about the development of HRP2 concentrations under the influence of anti-malarial drugs. HRP2 levels were determined in cell medium mixture, cellular compartment, and in culture supernatant using a double-site sandwich ELISA specific for HRP2. Characteristic increases in the overall HRP2 levels were found during the later ring and the trophozoite stages. Throughout the later schizont development, rupture, and reinvasion, however, the HRP2 levels remained comparatively stable. When the cultures were exposed to serial dilutions of anti-malarial drugs, a distinct inhibition of HRP2 production was seen with increasing concentrations of drugs, resulting in sigmoid dose-response curves, similar to those obtained from conventional drug sensitivity assays. HRP2 therefore allows for a very accurate estimation of parasite development and its inhibition and may therefore be ideally suited for use in drug sensitivity or bioassays.
Noedl
Harald
H
Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. harald.noedl@univie.ac.at
Wongsrichanalai
Chansuda
C
Miller
Robert Scott
RS
Myint
Khin Saw Aye
KS
Looareesuwan
Sornchai
S
Sukthana
Yaowalark
Y
Wongchotigul
Varee
V
Kollaritsch
Herwig
H
Wiedermann
Gerhard
G
Wernsdorfer
Walther H
WH
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D000099053:Histidine-Rich Glycoprotein
D000962:Antimalarials; D037621:Artemisinins; D011506:Proteins; D015800:Protozoan Proteins; D012717:Sesquiterpenes; D000099053:Histidine-Rich Glycoprotein; D000077332:Artesunate; D015767:Mefloquine