Hemolytic C-Type Lectin CEL-III from Sea Cucumber Expressed in Transgenic Mosquitoes Impairs Malaria Parasite Development

PLoS Pathogens

Yoshiaki Kouzuma¹  Marcelo Jacobs-Lorena²  Anil K Ghosh²  Daisuke Kondoh³  Shigeto Yoshida³  Yohei Shimada³  Robert E Sinden⁴ 

[1] College of Agriculture, Ibaraki University, Ami-machi, Inashiki-gun, Ibaraki, Japan;Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America;Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan;Infection and Immunity Section, Division of Cell and Molecular Biology, Imperial College London, South Kensington, London, United Kingdom

关键词: Mosquitoes;    Red blood cells;    Plasmodium;    Malarial parasites;    Blood;    Malaria;    Oocysts;    Parasitic diseases;   

DOI  :  10.1371/journal.ppat.0030192

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 IC50 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.

【 授权许可】

CC BY