Using bacteria to express and display anti-Plasmodium molecules in the mosquito midgut.
Bacteria capable of colonizing mosquito midguts are attractive vehicles for delivering anti-malaria molecules. We genetically engineered Escherichia coli to display two anti-Plasmodium effector molecules, SM1 and phospholipase-A(2), on their outer membrane. Both molecules significantly inhibited Plasmodium berghei development when engineered bacteria were fed to mosquitoes 24h prior to an infective bloodmeal (SM1=41%, PLA2=23%). Furthermore, prevalence and numbers of engineered bacteria increased dramatically following a bloodmeal. However, E. coli survived poorly in mosquitoes. Therefore, Enterobacter agglomerans was isolated from mosquitoes and selected for midgut survival by multiple passages through mosquitoes. After four passages, E. agglomerans survivorship increased from 2 days to 2 weeks. Since E. agglomerans is non-pathogenic and widespread, it is an excellent candidate for paratransgenic control strategies.
Riehle
Michael A
MA
Department of Microbiology and Molecular Immunology, Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.
Moreira
Cristina K
CK
Lampe
David
D
Lauzon
Carol
C
Jacobs-Lorena
Marcelo
M
D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000913:Antibodies, Protozoan / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005818:Genetic Engineering; D010962:Plasmodium berghei / Q000276:immunology*
D000913:Antibodies, Protozoan