A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria (Publications)
selective toward DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drug-resistant parasite isolates. Favorable pharmacokinetic [...] childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy [...] DSM265 has advantages over current treatment options that are dosed daily or are...
Bottlenecks and the maintenance of minor genotypes during the life cycle of <em>Trypanosoma brucei</em> (Publications)
minimum of several hundred parasites survived transmission from a tsetse fly to a mouse, or vice versa, and contributed to the infection in the new host. In contrast, the parasites experienced a pronounced [...] African trypanosomes are digenetic parasites that undergo part of their developmental cycle in mammals and part in tsetse flies. We established a novel technique to monitor the population dynamics of [...] sequences in a non-transcribed region of the genome. Infections were initiated...
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria (Publications)
selective toward DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drug-resistant parasite isolates. Favorable pharmacokinetic [...] childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy [...] DSM265 has advantages over current treatment options that are dosed daily or are...
Critical roles of glycosylphosphatidylinositol for <em>Trypanosoma brucei</em> (Publications)
TbGPI10; therefore, GPI synthesis is essential for growth of mammalian stage parasites. Procyclic form cells (insect stage parasites) lacking the surface coat proteins because of disruption of TbGPI10 are viable [...] Trypanosoma brucei, the protozoan parasite responsible for sleeping sickness, evades the immune response of mammalian hosts and digestion in the gut of the insect vector by means of its coat proteins tethered [...] cell surface via glycosylphosphatidylinositol (GPI) anchors. To...
Analysis of subtelomeric virulence gene families in <em>Plasmodium falciparum</em> by comparative transcriptional profiling (Publications)
Plasmodium falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. Members of these families are uniformly positioned within heterochromatic [...] to variegated expression. The best-studied example is that of the var family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 undergoes antigenic [...] role in endogenous gene transcription by comparative genome-wide...
The developmental lipidome of <em>Nippostrongylus brasiliensis</em> (Publications)
used as a model to study the immunobiology of parasitic nematodes. It is a member of the Strongylida-a large order of socioeconomically important parasitic nematodes of animals. Lipids are known to play [...] of key free-living and parasitic stages of N. brasiliensis. This study provides lipidomic resources to underpin the detailed exploration of lipid biology in this model parasitic nematode.
Life cycle maintenance and drug-sensitivity assays for early drug discovery in <em>Schistosoma mansoni</em> (Publications)
and promote antischistosomal drug discovery, setting up a drug-screening flow with schistosome parasites remains challenging. Whereas numerous different protocols to obtain and cultivate schistosomes have [...] been published, those describing the drug-screening process are scarce, and none gather together parasite cultivation and early drug discovery procedures. To help overcome this hurdle, we provide here a [...] mansoni life cycle in a laboratory setting, as well as the means of retrieving...
The essential malaria protein <em>Pf</em>CyRPA targets glycans to invade erythrocytes (Publications)
studies. Transgenic parasite lines expressing endogenous PfCyRPA with single amino acid exchange mutants indicated that the lectin activity of PfCyRPA has an important role in parasite invasion. Blocking [...] Summary Plasmodium falciparum is a human-adapted apicomplexan parasite that causes the most dangerous form of malaria. P. falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein [...] with small molecules or with lectin-site-specific monoclonal antibodies can...
7-<em>N</em>-substituted-3-oxadiazole quinolones with potent antimalarial activity target the cytochrome <em>bc</em>1 complex (Publications)
antimalarial chemotypes, we screened the Janssen Jumpstarter library against the P. falciparum asexual parasite and identified the 7-N-substituted-3-oxadiazole quinolone hit class. We established the structu [...] pyrimidine biosynthesis and an established antimalarial target. Profiling against drug-resistant parasites confirmed that WJM228 confers resistance to the Q(o) site but not Q(i) site mutations, and in a [...] of cyt b. Consistent with other cyt b targeted antimalarials, WJM228...
Capture-based enrichment of <em>Theileria parva </em>DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional... (Publications)
Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not [...] high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ~54K single [...] 44, reflecting a degree of genetic differentiation between cattle- and...
