Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.
The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions.
Yoshida
Shigeto
S
Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan. shigeto@jichi.ac.jp
Shimada
Yohei
Y
Kondoh
Daisuke
D
Kouzuma
Yoshiaki
Y
Ghosh
Anil K
AK
Jacobs-Lorena
Marcelo
M
Sinden
Robert E
RE
D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism / Q000469:parasitology; D003001:Cloning, Molecular; D048016:Cucumaria / Q000737:chemistry / Q000378:metabolism*; D004064:Digestive System; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D015870:Gene Expression; D006461:Hemolysis; D053878:Hemolytic Agents / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D066298:In Vitro Techniques; D007303:Insect Vectors / Q000235:genetics / Q000378:metabolism / Q000469:parasitology; D037102:Lectins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008288:Malaria; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D010963:Plasmodium falciparum / Q000472:pathogenicity; D051381:Rats; D011914:Rats, Inbred BN
C402644:CEL-III lectin, Cucumaria echinata; D053878:Hemolytic Agents; D037102:Lectins