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After the Mosquito Stage, Plasmodium Falciparum Re-Starts its Set Of Var-Genes

As the proteins produced by P. falciparum to attach infected red blood cells to a vessel wall are located on the outer cell surface (p. 55), they are recognised by our immune cells, resulting in the production of antibodies, which may inhibit attachment

Malaria life cycle. Left, composition of the various var genes activated in P. falciparum before feeding a mosquito. Right, composition in human blood after the mosquito bite and the liver stage.
Malaria life cycle. Left, composition of the various var genes activated in P. falciparum before feeding a mosquito. Right, composition in human blood after the mosquito bite and the liver stage.

To circumvent the inhibition, each P. falciparum strain contains a family of about sixty genes – so-called var-genes -, each of which encodes a different surface molecule. During its blood stage, P. falciparum activates these 60 genes in an as yet unknown order to stepwise change its attachment molecules, thereby escaping antibody inhibition. The order and regulation of the stepwise change has remained obscure although being of great importance for both drug and vaccine development. Only by studying a number of volunteers, all infected by mosquito bites with the same P. falciparum isolate in controlled vaccination experiments, enabled us to reveal that, after transmission by a mosquito, P. falciparum in the onset of the blood stage always activates the same group of var genes simultaneously, apparently to test the suitability of several proteins for attachment to the vessel walls, in case the new host carries antibodies against some of them from a previous infection.


Bachmann A. et al., PLoS Pathog 2016, 12:e1005538

Anna Bachmann, Ralf Krumkamp, Judith Scholz, Egbert Tannich and external cooperation partners (see publication)