Transporters As Targets

The work of Dr Henry Staines on transporters is providing new insight into the biology of the malarial parasite, Plasmodium falciparum, and identifying possible new targets for drug development.

Transporters move small substances across cell membranes, performing critical functions that often make them attractive targets for new drugs. With national and international collaborators, Dr Staines has characterised two P. falciparum transporters, the iron transporter, PfVIT, and the calcium transporter, PfCAX. Iron and calcium are both essential to the malarial parasite’s survival but can also be toxic at high levels.

Using rodent models, PfVIT and PfCAX were shown to play critical roles in the parasite in stopping the toxic effects of too much iron and calcium, respectively. PfVIT is particularly important to the parasite during liver cell infection, while PfCAX is essential when the parasite residues within its mosquito vector.

Other recent studies have revealed how increased glucose uptake by mobilisation of host intracellular glucose transporters (GLUT1) to the surface of liver cells and arginine uptake in liver cells by host arginine transporters are both crucial aspects of parasite infection.

Publications

• Slavic K et al. A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium. Nat Commun. 2016;7:10403. doi: 10.1038/ncomms10403.

• Guttery D et al. The Plasmodium berghei Ca²⁺/H⁺ exchanger, PbCAX, is essential for tolerance to environmental Ca²⁺ during sexual development. PLoS Pathog. 2013;9:e1003191. doi: 10.1371/journal.ppat.1003191.

• Meireles P et al. GLUT1-mediated glucose uptake plays a crucial role during Plasmodium hepatic infection. Cell Microbiol. 2017;19: e12646. doi: 10.1111/cmi.12646.

• Meireles P et al. Uptake and metabolism of arginine impact Plasmodium development in the liver. Sci Rep. 2017;7:4072. doi: 10.1038/s41598-017-04424-y.