Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion (PNAS), Dinglasan et al.

This is a recent paper from the same group that demonstrated that disruption of Anopheles gambiae aminopeptidase N in the mosquito midgut prevented the development of P. falciparum. In this paper, they demonstrated a few key principles:

1) Condroitan sulfate proteoglycans localized to the luminal surface of A. gambiae mosquito midgut epithelial cells
2) Condroitan sulfate A and E bound to P. falciparum ookinetes after overnight co-incubation
3) Knockdown of the upstream enzyme Anopheles gambiae peptide O-xylosyltransferase (AgOXT1) with RNAi reduced expression of CS but (interestingly) not HS in the mosquito midgut.
4) Compared with the GFP control group, the AgOXT1 knockdown group had less oocyst formation in the mosquito midgut after the mosquitoes were fed a P. falciparum bloodmeal, implying that ookinete invasion was thwarted due to the lack of CS.

The overall conclusion is that Plasmodium ookinetes may use structurally specific chondroitan sulfate moieties to attach to and invade mosquito midgut epithelial cells. The authors note that the CS that they investigated is structurally different than the CS that Plasmodium infected RBCs use to adhere to during sequestration in the placenta.

Reference: PNAS. 2007 Sep 14
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