Scientists have identified a protein that plays a key role in the lifecycle of the malaria parasite, paving the way for novel treatments that could save thousands of lives worldwide.
Malaria remains a significant threat to human health with approximately 216 million cases annually and over 400,000 deaths worldwide, according to researchers from University of Glasgow in the UK.
It is caused by the Plasmodium parasite, which has a complex lifecycle involving transmission to humans via the Anopheles mosquito.
Researchers including those from the Wellcome Sanger Institute in the UK showed that a regulator protein, AP2-G, may hold the key to finding new approaches to prevent the disease.
The study, published in the journal Nature Microbiology, found that AP2-G is the master switch in the parasite that controls a pattern of gene expression essential for the parasite to successfully infect mosquitoes.
The findings highlight a potential new target for approaches that may unlock a new potential way to prevent the spread of this devastating disease.
"This new experimental approach enabled us to confirm that AP2-G controls vitally important developmental pathways in gametocytes, and that it controls further gene expression and development," said Andy Waters, from the University of Glasgow.
"We also showed that both male and female specific genes are expressed and that blocking the expression of one of these genes resulted in parasites that could not make male gametocytes, thus ending the parasite lifecycle," said Waters.
"Foremost, our work has the potential to uncover further novel biology as well as strategies that will prevent the spread of this devastating disease," he said.
The Plasmodium parasite has a complex lifecycle, which relies on a cycle of transmission between humans and mosquitoes.
The disease-causing forms grow asexually inside red blood cells of an infected human host. These forms are not infectious to mosquitoes.
At a key stage in the lifecycle, specialised forms of the parasites called gametocytes are produced in the blood.
These gametocytes exist as male and female forms and they can initiate the mosquito phase of the parasite life cycle when they get taken up by a female mosquito biting an infected human.
"What led us to the breakthrough was that we designed a new experimental parasite line in which we could dial the amount of AP2-G up and down," said Oliver Billker, from the Wellcome Sanger Institute.
"By dialing AP2-G up, we managed to turn all blood stage parasites into parasites that were able to infect mosquitoes. This is how we know AP2-G is the master regulator," said Billker.
By switching on the gene, researchers were able to convert almost all parasites into gametocytes.
"Even the parasites that have already invaded the red blood cells and were just hours away from asexual division could change into fully functional sexual forms -- an act that was previously thought to require at least one cycle of further multiplication in preparation," Katarzyna Modrzynska, from the University of Glasgow.
