A groundbreaking study led by the Swiss Tropical and Public Health Institute (Swiss TPH) and Griffith University’s Institute for Glycomics has uncovered a crucial mechanism behind the invasion of human red blood cells by the malaria parasite, Plasmodium falciparum. Published in Cell Reports, the research sheds light on the role of a sugar molecule called sialic acid in this invasion process, with significant implications for malaria vaccine and drug development.
Despite global efforts to combat malaria, which recorded 249 million cases and 608,000 deaths in 2022, the disease remains a formidable health threat worldwide.
Plasmodium falciparum, the deadliest malaria parasite, causes severe malaria and accounts for the majority of malaria-related fatalities. Clinical symptoms of malaria are primarily triggered by the multiplication of these parasites within red blood cells.
Key Component Identified for Malaria Invasion
While scientists have long recognized that P. falciparum invades human red blood cells, the specific targets of the parasite’s binding process have remained elusive. In particular, the role of the malaria protein cystein-rich protective antigen (CyRPA) in this invasion has been poorly understood.
A collaborative research team spanning six institutions, led by experts from Swiss TPH in Switzerland and Griffith University’s Institute for Glycomics in Australia, conducted an in-depth examination of CyRPA’s binding properties. Their findings, published in Cell Reports, revealed that sialic acid, a sugar molecule on the surface of red blood cells, plays a pivotal role in the invasion process.
“We have demonstrated that P. falciparum CyRPA specifically binds to a carbohydrate structure containing sialic acid on the surface of red blood cells. This discovery elucidates the critical function of CyRPA in host cell invasion and provides insights into the inhibitory activity of CyRPA-specific antibodies against the parasite,” explained Gerd Pluschke, Group Leader of Molecular Immunology at Swiss TPH and co-corresponding author of the study.
Malaria Parasite Adaptation to Humans
Furthermore, the study uncovered how the malaria parasite has adapted to infect humans specifically. Unlike other primates, humans produce only one type of sialic acid, known as Neu5Ac. The researchers found that P. falciparum exhibits a strong preference for Neu5Ac, underscoring its adaptation to target human hosts.
“This genetic divergence between humans and closely related primates likely contributes to the species-specific targeting of malaria parasites. Our study provides evidence that the human form of sialic acid, Neu5Ac, is favored by P. falciparum, shedding light on the parasite’s adaptation to human hosts,” remarked Michael Jennings, Acting Director of the Institute for Glycomics and co-corresponding author of the paper.
Implications for Vaccine and Drug Development
The discovery of CyRPA’s crucial role in host cell invasion offers promising avenues for malaria vaccine and drug development. Existing vaccines targeting P. falciparum show moderate efficacy, particularly against the blood stage of the disease.
“The identification of CyRPA as a key player in host cell invasion bolsters the rationale for evaluating CyRPA as a blood stage vaccine target,” stated Pluschke.
Moreover, as drug resistance poses a significant challenge in malaria treatment, the study’s findings pave the way for novel antimalarial drugs. Small molecule inhibitors that disrupt CyRPA’s binding activity demonstrated efficacy in inhibiting malaria replication, offering hope for urgently needed therapeutics.
As the global community continues its fight against malaria, advancements in understanding the parasite’s invasion mechanisms hold promise for more effective prevention and treatment strategies.
