Solute carriers affect Anopheles stephensi survival and Plasmodium berghei infection in the salivary glands

Abstract

Malaria is caused by mosquito-borne Plasmodium spp. parasites that must infect and survive within mosquito salivary glands (SGs) prior to host transmission. Recent advances in transcriptomics and the complete genome sequencing of mosquito vectors have increased our knowledge of the SG genes and proteins involved in pathogen infection and transmission. Membrane solute carriers are key proteins involved in drug transport and are useful in the development of new interventions for transmission blocking. Herein, we applied transcriptomics analysis to compare SGs mRNA levels in Anopheles stephensi fed on non-infected and P. berghei-infected mice. The A. stephensi solute carriers prestinA and NDAE1 were up-regulated in response to infection. These molecules are predicted to interact with each other, and are reportedly involved in the maintenance of cell homeostasis. To further evaluate their functions in mosquito survival and parasite infection, these genes were knocked down by RNA interference. Knockdown of prestinA and NDAE1 resulted in reduction of the number of sporozoites in mosquito SGs. Moreover, NDAE1 knockdown strongly impacted mosquito survival, resulting in the death of half of the treated mosquitoes. Overall, our findings indicate the importance of prestinA and NDAE1 in interactions between mosquito SGs and Plasmodium, and suggest the need for further research.Over the last 15 years, massive prevention measures and new treatment tools have greatly decreased the global malaria burden. However, despite these advances, about 214 million new malaria cases and 438,000 associated deaths were registered in 2015 alone 1 . Malaria is caused by mosquito-borne Plasmodium parasites. In particular, adult female mosquitoes of the genus Anopheles are efficient Plasmodium vectors in many diverse ecosystems 2, 3 . Anopheles stephensi is a competent vector for both Plasmodium falciparum and P. vivax, the most virulent malaria-associated species 3 , as well as for Plasmodium species that infect rodents and, thus, this mosquito species is widely used as a laboratory model. A. stephensi is found throughout the Indian subcontinent-with its territory extending from the Arabian Peninsula, Iran, and Iraq, to Bangladesh, southern China, Myanmar, and Thailand 4 .Malaria transmission from mosquitoes to vertebrate hosts occurs through the mosquito's salivary glands (SGs), and for this reason many studies have focused on this organ to develop new malaria control measures [5][6][7][8][9] . Sporozoite invasion of mosquito SGs is receptor-mediated, and involves several parasite and SG proteins 10,11 . Characterization of the salivary components involved in parasite infection and transmission would greatly enhance our understanding of the mosquito-host-pathogen interface, and potentially reveal candidate targets for malaria prevention and control.

Rhipicephalus bursa Sialotranscriptomic Response to Blood Feeding and Babesia ovis Infection: Identification of Candidate Protective Antigens

“…Thirty female ticks per group were injected in the trochanter-coxae articulation with 69 nL of gene specific dsRNA (1 × 10 11 to 1 × 10 12 molecules) or unrelated dsRNA as control, using the nano-injector (Nanoject, Drummond Scientific, PA, USA). The mouse β- 2-microglobulin dsRNA (dsβ 2M ) (GenBank: NM_009735 ) was used as control (Couto et al, 2017 ). After dsRNA injection, female ticks were held in a humidity chamber for 4 h after which they were allowed to feed on the splenectomized lamb infected with B. ovis together with 30 male ticks per feeding cell.…”

Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi

“…Its knockdown decreased the number of sporozoites in mosquito salivary glands. [19,20,21]. Asteglut1 help to defend against P. berghei might through regulating midgut glucose level.…”

Glucose transporter Glut1 influences Plasmodium berghei infection in Anopheles stephensi

“…Knockdown of both genes reduces the burden of P. berghei sporozoites in the salivary glands. [18,19,20].…”

“…Blocking AGAP007752 in mosquito salivary glands inhibits Plasmodium sporozoite infection [18,19,20]. However, the function of other GLUTs remains unknown.…”