A5056082984- Malaria Research and Control
- Drug Transport and Resistance Mechanisms
- Trypanosoma species research and implications
- Parasites and Host Interactions
- HIV/AIDS drug development and treatment
- Invertebrate Immune Response Mechanisms
- Parasite Biology and Host Interactions
- Insect Resistance and Genetics
- Toxoplasma gondii Research Studies
- Hepatitis Viruses Studies and Epidemiology
- Pharmacological Effects and Toxicity Studies
- Phytochemicals and Antioxidant Activities
- Research on Leishmaniasis Studies
- Tea Polyphenols and Effects
- Morinda citrifolia extract uses
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Parasitic Infections and Diagnostics
- Iron Metabolism and Disorders
University of Lisbon
2013-2022
Instituto de Medicina Molecular João Lobo Antunes
2016-2021
St George's Hospital
2016
University of London
2016
University of Belgrade
2011-2015
St George's, University of London
2009-2013
A Plasmodium falciparum hexose transporter (PfHT) has previously been shown to be a facilitative glucose and fructose transporter. Its expression in Xenopus laevis oocytes the use of analogue inhibitor permitted chemical validation PfHT as novel drug target. Following recent re-annotations P. genome, other putative sugar transporters have identified. To investigate further if is key supplier extend studies different stages spp., we functionally analysed both human parasite rodent berghei...
Abstract Iron is an essential micronutrient but also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family proteins. Here we study VIT homologue from malaria parasites Plasmodium falciparum (PfVIT) berghei (PbVIT). PfVIT-mediated transport in heterologous expression system saturable ( K m ∼14.7 μM), selective for Fe 2+ over other divalent...
During blood infection, malarial parasites use D-glucose as their main energy source. The Plasmodium falciparum hexose transporter (PfHT), which mediates the uptake of into parasites, is essential for survival asexual blood-stage parasites. Recently, genetic studies in rodent malaria model, berghei, found that orthologous (PbHT) expressed throughout parasite's development within mosquito vector, addition to being during intraerythrocytic development. Here, using a D-glucose-derived specific...
Ca2+ contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due its varied essential roles, free is tightly regulated by complex mechanisms. These mechanisms are therefore interest as putative drug targets. One pathway homeostatic control apicomplexans uses Ca2+/H+ exchanger (a member cation family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised asexual blood stage parasites. To determine...
Background.The mechanism of action artemisinins against malaria is unclear, despite their widespread use in combination therapies and the emergence resistance.Results.Here, we report expression PfATP6 (a SERCA pump) yeast demonstrate its inhibition by artemisinins.Mutations identified field isolates (such as S769N) laboratory clones L263E) decrease susceptibility to artemisinins, whereas they increase unrelated inhibitors such cyclopiazonic acid.As predicted from model, Plasmodium falciparum...
Here we have investigated the inhibitory properties of green tea catechins on Plasmodium falciparum hexose transporter (PfHT), Babesia bovis 1 (BboHT1) and mammalian facilitative glucose transporters, GLUT1 GLUT5, expressed in Xenopus laevis oocytes. (-)-Epicatechin-gallate (ECG) (-)-epigallocatechin-gallate (EGCG) inhibited D-glucose transport by PfHT, D-fructose with apparent K(i) values between 45 117 microM. BboHT1 was more potently ungallated (-)-epicatechin (EC) (-)-epigallocatechin...
We sought to establish if methylene homologues of artemisone are biologically more active and stable than artemisone. The analogy is drawn with the conversion natural O- N-glycosides into C-glycosides that may possess enhanced biological activities stabilities. Dihydroartemisinin was converted 10β-cyano-10-deoxyartemisinin hydrolyzed α-primary amide. Reduction β-cyanide α-amide provided respective methylamine epimers upon treatment divinyl sulfone gave β- α-methylene homologues,...
Parasite-derived PVM-resident proteins are critical for complete parasite development inside hepatocytes, although the function of most these remains unknown. Here, we show that upregulated in infectious sporozoites 4 (UIS4) protein, resident at PVM, interacts with host cell actin. By suppressing filamentous actin formation, UIS4 avoids elimination. Host dynamics increases around UIS4-deficient parasites, which is associated subsequent Notably, elimination impaired significantly by...
Apicomplexa are a large group of eukaryotic, single-celled parasites, with complex life cycles that occur within wide range different microenvironments. They include important human pathogens such as Plasmodium, the causal agent malaria, and Toxoplasma, which causes toxoplasmosis most often in immunocompromised individuals. Despite environmental differences their cycles, these parasites retain ability to obtain nutrients, remove waste products, control ion balances. achieve this flexibility...
Parasite-derived PVM-resident proteins are critical for complete parasite development inside hepatocytes (Hanson et al., 2013; Mueller 2005), although the function of most these remains unknown. Here, we show that Up-Regulated in Infectious Sporozoites 4 (UIS4) protein, resident at PVM, interacts with host-cell actin. By suppressing filamentous actin formation UIS4 avoids elimination. Host-cell dynamics increases around UIS4-deficient parasites, which is associated subsequent Notably,...