The mechanism of the most commonly used antimalarial drugs unveiled

For centuries, quinoline has been an effective compound in antimalarial drugs, although no one knew its mode of action in vivo.

Today, a team led by the Weizmann Institute has discovered its mechanism in infected red blood cells in near-native conditions, by using the ESRF, Alba Synchrotron and BESSY. They publish their results in PNAS.

Malaria remains one of the biggest killers in low-income countries. Estimates of the number of deaths each year range from 450,000 to 720,000, with the majority of deaths happening in Africa. In the last two decades, the malaria parasite has evolved into drug-resistant strains. “Recently, the increasing geographical spread of the species, as well as resistant strains has concerned the scientific community, and in order to improve antimalarial drugs we need to know how they work precisely”, explains Sergey Kapishnikov, from the University of Copenhagen, in Denmark, and the Weizmann Institute, in Israel, and leader of the study.

Plasmodium parasite, when infecting a human, invades a red blood cell, where it ingests hemoglobin to grow and multiply. Hemoglobin releases then iron-containing heme molecules, which are toxic to the parasite. However, these molecules crystallise into hemozoin, a disposal product formed from the digestion of blood by the parasite that makes the molecules inert. For the parasite to survive, the rate at which the heme molecules are liberated must be slower or the same as the rate of hemozoin crystallization. Otherwise there would be an accumulation of the toxic heme within the parasite.

>Read more on the ESRF website

Image (taken from BESSY II article): The image shows details such as the vacuole of the parasites (colored in blue and green) inside an infected blood cell.
Credit:
S. Kapishnikov

Two other institutes, BESSY II at HZB and ALBA Synchrotron, have participated in this research. Please find here their published articles:

> X-ray microscopy at BESSY II reveal how antimalaria-drugs might work

> The mechanism of the most commonly used antimlalarial drugs in near- native conditions unveiled

Scienstists make breakthrough in creating universal blood type

Enzymes in the human gut can convert A blood type into O.

Half of all Canadians will either need blood or know someone who needs it in their lifetime. Researchers from the University of British Columbia have made a breakthrough in their technique for converting A and B type blood into universal O, the type that is most needed by blood services and hospitals because anyone can receive it.
In a paper published in Nature Microbiology, Stephen Withers and a multidisciplinary team of researchers from the University of British Columbia show how they successfully converted a whole unit of A type blood to O type using their system.  They were able to remove the sugars from the surface of the red blood cells with help from a pair of enzymes that were isolated from the gut microbiome of an AB+ donor.
The Canadian Light Source (CLS) at the University of Saskatchewan (UofS) played a critical role in understanding the structure of a previously unknown enzyme that was part of this pair. The researchers were unable to identify what this unique enzyme looked like from the gene sequence they had.  Crystallography, done at the CLS, was crucial for the researchers to understand how this enzyme works and why it had a particular affinity for the A type blood.

>Read more on the Canadian Light Source website