SOAP, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development.
An 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-to-oocyst differentiation in mosquitoes.
Dessens
Johannes T
JT
Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, SW7 2AZ, UK. j.dessens@imperial.ac.uk
Sidén-Kiamos
Inga
I
Mendoza
Jacqui
J
Mahairaki
Vassiliki
V
Khater
Emad
E
Vlachou
Dina
D
Xu
Xiao-Jin
XJ
Kafatos
Fotis C
FC
Louis
Christos
C
Dimopoulos
George
G
Sinden
Robert E
RE
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000852:Anopheles / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D002460:Cell Line; D004064:Digestive System / Q000378:metabolism / Q000382:microbiology; D005260:Female; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008288:Malaria / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D033661:Oocysts / Q000254:growth & development*; D010641:Phenotype; D010962:Plasmodium berghei / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D019476:Insect Proteins; D007797:Laminin; D015800:Protozoan Proteins; C482106:secreted ookinete adhesive protein, Plasmodium