Transmission of malaria from one human to another depends upon the successful sporogonic development of the parasite in vector mosquitoes. If the mosquito does not allow the ingested parasites to develop they die, and the transmission of malaria is blocked. Interruption of the malaria parasite development in vector mosquitoes could, therefore, be a useful strategy to block the spread of malaria. To design such strategies, however, understanding of the molecular, biochemical and cellular aspects of parasite development in vector mosquitoes is essential. Development of the malaria parasite in the mosquito is complex. After being ingested by a susceptible mosquito, the parasite follows an elaborate developmental scheme. Expression of stage-specific parasite genes and interaction of the parasite with various tissues and molecules in the mosquitoes, accompany dramatic morphologic changes. Each of the developmental changes is compartmentalized in distinct cellular and biochemically defined region, and occur sequentially. The development in the mosquito, therefore, is a challenge to the parasite. Most parasites do not develop to mature ookinetes in the midgut lumen or fail to invade the in the midgut wall. Therefore, molecules involved with the parasite/mosquito midgut interaction are crucial determinants of the sporogonic development of the parasite. To identify the molecules we investigate the ookinete interaction with the midgut epithelium and the survival of the parasite in the vector. Also of the hundreds of mosquitoes only a few species allow Plasmodium development, and of these a few are vectors. Even in the mosquitoes that are known as good vectors of malaria only a fraction of the ingested parasite survives. These suggest that all mosquitoes are inherently refractory to malaria parasites. Understanding the mechanism of parasite killing by mosquitoes can be useful in designing malaria transmissiojn blocking strategies. We, therefore, study insect responses to malaria parasites. These studies may lead to development of novel strategies to control malaria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000811-04
Application #
6431691
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Shahabuddin, Mohammed (2002) Do Plasmodium ookinetes invade a specific cell type in the mosquito midgut? Trends Parasitol 18:157-61
Silva-Neto, Mario A C; Atella, Georgia C; Shahabuddin, Mohammed (2002) Inhibition of Ca2+/calmodulin-dependent protein kinase blocks morphological differentiation of plasmodium gallinaceum zygotes to ookinetes. J Biol Chem 277:14085-91
Wang, P; Conrad, J T; Shahabuddin, M (2001) Localization of midgut-specific protein antigens from Aedes aegypti (Diptera: Culicidae) using monoclonal antibodies. J Med Entomol 38:223-30
Shahabuddin, M; Costero, A (2001) Spatial distribution of factors that determine sporogonic development of malaria parasites in mosquitoes. Insect Biochem Mol Biol 31:231-40
Park, S S; Shahabuddin, M (2000) Structural organization of posterior midgut muscles in mosquitoes, Aedes aegypti and Anopheles gambiae. J Struct Biol 129:30-7
Killeen, G F; Foy, B D; Shahabuddin, M et al. (2000) Tagging bloodmeals with phagemids allows feeding of multiple-sample arrays to single cages of mosquitoes (Diptera: Culicidae) and the recovery of single recombinant antibody fragment genes from individual insects. J Med Entomol 37:528-33
Schneider, D; Shahabuddin, M (2000) Malaria parasite development in a Drosophila model. Science 288:2376-9
Zieler, H; Garon, C F; Fischer, E R et al. (2000) A tubular network associated with the brush-border surface of the Aedes aegypti midgut: implications for pathogen transmission by mosquitoes. J Exp Biol 203:1599-611
Zieler, H; Nawrocki, J P; Shahabuddin, M (1999) Plasmodium gallinaceum ookinetes adhere specifically to the midgut epithelium of Aedes aegypti by interaction with a carbohydrate ligand. J Exp Biol 202:485-95
Shahabuddin, M; Vinetz, J M (1999) Chitinases of human parasites and their implications as antiparasitic targets. EXS 87:223-34

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