SOAP, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development

Abstract

SummaryAn essential, but poorly understood part of malaria transmission by mosquitoes is the development of the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall. For successful oocyst formation newly formed ookinetes in the midgut lumen must enter, traverse, and exit the midgut epithelium to reach the midgut basal lamina, processes collectively known as midgut invasion. After invasion ookinete-to-oocyst transition must occur, a process believed to require ookinete interactions with basal lamina components. Here, we report on a novel extracellular malaria protein expressed in ookinetes and young oocysts, named secreted ookinete adhesive protein (SOAP). The SOAP gene is highly conserved amongst Plasmodium species and appears to be unique to this genus. It encodes a predicted secreted and soluble protein with a modular structure composed of two unique cysteine-rich domains. Using the rodent malaria parasite Plasmodium berghei we show that SOAP is targeted to the micronemes and forms high molecular mass complexes via disulphide bonds. Moreover, SOAP interacts strongly with mosquito laminin in yeast-two-hybrid assays. Targeted disruption of the SOAP gene gives rise to ookinetes that are markedly impaired in their ability to invade the mosquito midgut and form oocysts. These results identify SOAP as a key molecule for ookinete-tooocyst differentiation in mosquitoes.

Essential role of membrane-attack protein in malarial transmission to mosquito host

“…A cDNA library was made from the mRNA as described (5). Sequence analysis using the BLAST program showed that this database includes ESTs of known ookinete stage-specific genes: 33 circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP); 18 von Willebrand factor A domain-related protein; 91 chitinase; and 216 secreted ookinete adhesive protein (9)(10)(11)(12).…”

The development of malaria parasites in the mosquito midgut

“…Other microneme proteins assigned to midgut traversal of P . berghei ookinetes include SOAP, WARP and CelTOS (cell‐traversal protein for ookinetes and sporozoites) (Yuda et al ., 2001; Dessens et al ., 2003; Kadota et al ., 2004; Li et al ., 2004; Kariu et al ., 2006; Ecker et al ., 2007, 2008; Kaneko et al ., 2015; Wirth et al ., 2015) (Table 1). …”

Laminin and the malaria parasite's journey through the mosquito midgut

“…Moreover, it was later shown that the same laminin could also bind to the SOAP (Dessens et al, 2003) and CTRP (Mahairaki et al, 2005) proteins of the ookinete. In order to investigate whether these biochemical laminin-parasite interactions and the association described above also serve a biological role in the survival of the parasite during the invasion of the mosquito midgut by P. berghei parasites, we took advantage of the dsRNA gene silencing technology (Fire et al, 1998).…”

“…Although very thorough descriptions exist for this process involving two different organisms, the specific molecular partners that make these interactions possible have not yet been identified (see Sinden, 2002). Several ookinete surface molecules, such as P25 and P28 (Siden-Kiamos et al, 2000), SOAP (secreted ookinete adhesive protein; Dessens et al, 2003) and CTRP (circumsporozoite protein and thrombospondin-related adhesive protein; Dessens et al, 1999), have been implicated in the process of midgut invasion but, to date, no putative receptor has been identified or proposed on the midgut epithelium. Direct or indirect binding to Plasmodium surface proteins has only been demonstrated for laminin (Vlachou et al, 2001;Arrighi and Hurd, 2002;Dessens et al, 2003;Adini and Warburg, 1999) and collagen IV (Arrighi and Hurd, 2002;Adini and Warburg, 1999), both components of all vertebrate (Miosge, 2001) and invertebrate (Hynes and Zhao, 2000) basal laminae, including the one surrounding the insect midgut on its haemocoel side.…”