Yukino Kobayashi (Gießen / DE), Annika Binder (Heidelberg / DE), Felix Mikus (Heidelberg / DE), Prof. Freddy Frischknecht (Heidelberg / DE), Ross Douglas (Gießen / DE)
Abstract text
Plasmodium requires active motility in order to spread and must traverse and invade mammalian and mosquito organs. Actin-like proteins (Alps) are apicomplexan-specific, highly divergent members of the actin superfamily. Alps are characterised by several unique regions and likely have critical functions during parasite infection. However, the functions and stage specific contributions of Alps in parasite progression are unknown.
The corresponding genes of Alp1 and Alp2b were knocked-out in Plasmodium berghei and the phenotypic impacts of these deletions on the parasites were investigated. Remarkably, the absence of Alp1 or Alp2b led to a drastic reduction or complete block of mosquito midgut colonisation at different steps of transmission respectively. Specifically, Alp1 was essential for the motility of ookinetes, which actively colonise mosquito midguts, while Alp2b was crucial for parasite fertilisation. Alp2b function in P. berghei was partially restored by P. falciparum Alp2b complementation, indicating a degree of cross-species conservation. Mutations of selected unique regions of P. berghei Alp2b prevented exflagellation, implicating these regions as critical contributors to Alp2b function and thus potential targeting regions.
Our study reveals the importance of Alps in Plasmodium transmission and the stage-specific contributions of these members of apicomplexan actin superfamily.