Comparison of analytical methods for the evaluation of antibody responses against epitopes of polymorphic protein antigens (Publications)
exposed protein antigens of the malaria parasite Plasmodium falciparum frequently harbor multiple dimorphic amino acid positions. These are associated with parasite immune evasion and represent a major obstacle [...] scence analysis (IFA) and Western blotting analysis, the mAbs nevertheless stained all analyzed parasite clones expressing MSP-1(43-53) variant sequences. When used for the evaluation of humoral immune
A <em>var</em> gene promoter controls allelic exclusion of virulence genes in <em>Plasmodium falciparum</em> malaria (Publications)
used by many organisms to mediate phenotypic variation of surface proteins. In the apicomplexan parasite Plasmodium falciparum, responsible for the severe form of malaria in humans, this is exemplified [...] represents a major virulence factor due to its central role in immune evasion and intravascular parasite sequestration. Mutually exclusive expression of PfEMP1 is controlled by epigenetic mechanisms involving [...] for our understanding of antigenic variation in P. falciparum. Furthermore,...
Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target (Publications)
small-molecule inhibitors of the enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) from parasitic protozoa. The successful synthesis of a variety of analogues of dUMP is described in which the [...] enzyme to give a measure of selectivity. The compounds were also tested in vitro against the intact parasites P. falciparum and L. donovani. A number of potent and selective inhibitors of the P. falciparum [...] determined. The correlation observed between the inhibition of the...
The N'-terminal domain of glyceraldehyde-3-phosphate dehydrogenase of the apicomplexan <em>Plasmodium falciparum</em> mediates GTPase Rab2-dependent... (Publications)
trophozoite stages of both liver and asexual blood stage parasites. During schizogony, pfGAPDH became associated with the periphery of the parasites and eventually accumulated in the apical region of merozoites [...] d that pfGAPDH was found in both the membrane-containing pellet and the supernatant fraction of parasite lysates. In contrast, pfAldolase was only found in the supernatant fraction. A quantitative binding
Improved inhibitors of trypanothione reductase by combination of motifs: synthesis, inhibitory potency, binding mode, and antiprotozoal activities (Publications)
reductase (TR) is an essential enzyme in the trypanothione-based redox metabolism of trypanosomatid parasites. This system is absent in humans and, therefore, offers a promising target for the development of [...] Chagas' disease. Over the past two decades, a variety of nonpeptidic small-molecule ligands of the parasitic enzyme were discovered. A current goal is to decipher the binding mode of these known inhibitors [...] d conjugates exhibit K(ic) values for TR as low as 0.51+/-0.1 muM and...
Global metabolic responses of NMRI mice to an experimental <em>Plasmodium berghei</em> infection (Publications)
disturbance of the gut microbial community caused by the parasite. Although several of the observed metabolic changes are also associated with other parasitic infections, the combination of metabolic changes and [...] Twelve female NMRI mice were infected intravenously with approximately 20 million P. berghei-parasitized erythrocytes. Urine and plasma samples were collected 4-6 h before infection, and at days 1, 2
Drug interaction studies of cabamiquine: ganaplacide combination against hepatic <em>Plasmodium berghei</em> (Publications)
against the liver and blood stages of Plasmodium infection. Cabamiquine (DDD107498, M5717) inhibits parasite protein synthesis, and ganaplacide (KAF156) inhibits protein trafficking, blocks the establishment [...] infection platform based on human hepatic cell lines that sustain infection by rodent P. berghei parasites. The in vivo efficacy of this drug combination was assessed against the liver stage of the P. berghei [...] viability. The drug combination was fully effective in preventing the...
Molecular assays for antimalarial drug resistance surveillance: a target product profile (Publications)
Artemisinin-based combination therapy is now the mainstay for malaria treatment. However, delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong [...] these studies are complex and both time- and resource-intensive. For multiple common antimalarials, parasite drug resistance has been correlated with specific genetic mutations, and the molecular markers [...] drug resistance offer a simple and powerful tool to monitor the emergence and...
Assessment of dual life stage antiplasmodial activity of British seaweeds (Publications)
collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds [...] generally had high selectivity indices (> 10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and [...] incurvus, all LS-active extracts showed dual activity versus both malarial...
Resistance to Artemisinin Combination Therapies (ACTs): do not forget the partner drug! (Publications)
remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased [...] discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious
