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Updated: Mar 22, 2026
Protocol for Plasmodium falciparum Infections in Mosquitoes and Infection Phenotype Determination
Published on: July 4, 2007
Mosquito Passage Dramatically Changes var Gene Expression in Controlled Human Plasmodium falciparum Infections
Anna Bachmann1, Michaela Petter2, Ralf Krumkamp3
1Bernhard Nocht Institute for Tropical Medicine, Department of Molecular Parasitology, Hamburg, Germany.
Abstract:
Virulence of the most deadly malaria parasite Plasmodium falciparum is linked to the variant surface antigen PfEMP1, which is encoded by about 60 var genes per parasite genome. Although the expression of particular variants has been associated with different clinical outcomes, little is known about var gene expression at the onset of infection. By analyzing controlled human malaria infections via quantitative real-time PCR, we show that parasite populations from 18 volunteers expressed virtually identical transcript patterns that were dominated by the subtelomeric var gene group B and, to a lesser extent, group A. Furthermore, major changes in composition and frequency of var gene transcripts were detected between the parental parasite culture that was used to infect mosquitoes and Plasmodia recovered from infected volunteers, suggesting that P. falciparum resets its var gene expression during mosquito passage and starts with the broad expression of a specific subset of var genes when entering the human blood phase.
Insights
The deadly malaria parasite Plasmodium falciparum shows consistent var gene expression patterns at infection onset. This suggests P. falciparum resets its gene expression after mosquito passage, beginning human infection with a specific subset of genes.
Area of Science:
- Molecular Parasitology
- Infectious Diseases
- Genomics
Background:
- The virulence of Plasmodium falciparum, the deadliest malaria parasite, is associated with the variant surface antigen PfEMP1.
- PfEMP1 is encoded by approximately 60 var genes per parasite genome, and specific variant expression correlates with clinical outcomes.
- Little is understood about var gene expression patterns at the very beginning of a malaria infection.
Purpose of the Study:
- To investigate var gene expression profiles in Plasmodium falciparum at the onset of controlled human malaria infections.
- To determine if P. falciparum alters its var gene expression during the mosquito transmission stage.
Main Methods:
- Controlled human malaria infections were established in 18 volunteers.
- Quantitative real-time PCR was employed to analyze var gene transcript patterns in Plasmodium parasites.
- Transcript profiles were compared between the parental parasite culture and parasites recovered from infected volunteers.
Main Results:
- Parasite populations from all 18 volunteers exhibited remarkably similar transcript patterns.
- These patterns were predominantly characterized by the expression of subtelomeric var gene group B, followed by group A.
- Significant shifts in the composition and frequency of var gene transcripts were observed between the initial culture and parasites in infected humans.
Conclusions:
- Plasmodium falciparum demonstrates a conserved and specific var gene expression profile at the initiation of human blood-stage infection.
- The data strongly suggest that P. falciparum resets its var gene expression during the mosquito passage.
- Upon entering the human bloodstream, the parasite begins infection by broadly expressing a defined subset of var genes.
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