WASHINGTON — British researchers said Thursday that they had identified a possible new target for the development of novel drugs against mosquito-borne malaria.
When malaria parasites invade red blood cells, they form an internal compartment in which they replicate many times before bursting out of the cell and infecting more cells, according to their study published in the journal PLOS Pathogens.
In order to escape red blood cells, the parasites have to break through both the internal compartment and the cell membrane using various proteins and enzymes.
Scientists at the Francis Crick Institute and the London School of Hygiene & Tropical Medicine have identified a key protein involved in this process.
Disrupting this protein reduces the efficiency of parasite escape, slowing down the rate of infection, they found.
“The parasite sits in its internal compartment inside the cell, surrounded by lots of proteins, a bit like a baby surrounded by amniotic fluid,” Mike Blackman, group leader at the Francis Crick Institute, said in a statement. “We focused on the most common protein, known as SERA5, assuming that it probably has an important role since there is so much of it.”
The team used genetic tools to knock out the gene responsible for producing SERA5 in malaria parasites and then took time-lapse video of the cells under a microscope.
They found that the parasites broke through the membranes faster than normal but many got stuck on their way out, meaning that they were less likely to invade other red blood cells.
Since malaria parasites don’t survive for long outside red blood cells, getting stuck on their way out means that they might die before they have a chance to infect another cell, the team said.
It turned out that parasites lacking SERA5 were about half as efficient as normal parasites at escaping and infecting new cells.
The team is now working with British pharmaceutical company GSK to see if SERA5 or one of the enzymes that it controls could be a potential drug target.
“Drug resistant malaria is a huge problem, so there is a real push to develop new drugs that work in a different way,” Blackman said. “None of the current antimalarials work by preventing the parasites from escaping red blood cells, so we think that the proteins and enzymes that help the parasites break free could be valuable new targets that we can design drugs for.” Xinhua-northboundasia.com