Scientists have identified a protein which allows malaria parasites to invade red blood cells, and could be targeted to stop the spread of the deadly infection. The finding paves the way for developing new drugs that can treat drug-resistant 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.
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 and Tropical Medicine in the UK have identified a key protein involved in this process.
Disrupting this protein reduces the efficiency of parasite escape, slowing down the rate of infection. The study was published in the journal PLOS Pathogens.
“The parasite sits in its internal compartment inside the cell, surrounded by lots of proteins, a bit like a baby surrounded by amniotic fluid,” said Mike Blackman, Group Leader at the Francis Crick Institute.
“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,” said Blackman.
The team used genetic tools to knock out the gene responsible for producing SERA5 in malaria parasites and then took a time-lapse video of the cells under a microscope.
The researchers 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. “Malaria parasites do not survive for long outside red blood cells, so if they get stuck on their way out, they might die before they have a chance to infect another cell,” said Christine Collins, the researcher at the Francis Crick Institute.
“We found that parasites lacking SERA5 were about half as efficient as normal parasites at escaping and infecting new cells,” Collins said.
The team are now working with 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,” said Blackman. “None of the current anti-malarials works 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,” he said.