Aedes aegypti SGS1 is critical for Plasmodium gallinaceum infection of both the mosquito midgut and salivary glands

BackgroundThe invasion of the mosquito salivary glands byPlasmodiumsporozoites is a critical step that defines the success of malaria transmission and a detailed understanding of the molecules responsible for salivary gland invasion could be leveraged towards control of vector-borne pathogens. Antibodies directed against the mosquito salivary gland protein SGS1 have been shown to reducePlasmodium gallinaceumsporozoite invasion ofAedes aegyptisalivary glands, but the specific role of this protein in sporozoite invasion and in other stages of thePlasmodiumlife cycle remains unknown.MethodsRNA interference and CRISPR/Cas9 were used to evaluate the role ofA. aegyptiSGS1 in theP. gallinaceumlife cycle.ResultsKnockdown and knockout of SGS1 disrupted sporozoite invasion of the salivary gland. Interestingly, mosquitoes lacking SGS1 also displayed fewer oocysts. Proteomic analyses confirmed the abolishment of SGS1 in the salivary gland of SGS1 knockout mosquitoes and revealed that the C-terminus of the protein is absent in the salivary gland of control mosquitoes. In silico analyses indicated that SGS1 contains two potential internal cleavage sites and thus might generate three proteins.ConclusionSGS1 facilitates, but is not essential for, invasion ofA. aegyptisalivary glands byP. gallinaceumand has a dual role as a facilitator of parasite development in the mosquito midgut. SGS1 could, therefore, be part of a strategy to decrease malaria transmission by the mosquito vector, for example in a transgenic mosquito that blocks its interaction with the parasite.