Malaria is a major human disease that has shown no evidence of declining despite years of drug therapy to treat infected humans and efforts to control its mosquito vectors. Alternative strategies to deal with this problem are clearly needed. Work has progressed in the area of antimalarial effector genes that can prevent the establishment of Plasmodium parasites in their mosquito hosts, but there is currently no way to deliver these genes and their products to mosquitoes in the wild. One method to deliver such genes is by transforming bacteria that normally live in mosquito midguts, like the gamma proteobacterium Enterobacter agglomerans, into gene product delivery vehicles. This proposal seeks to tackle one aspect of modifying E. agglomerans into an effective antimalarial reagent, namely the development of efficient protein secretion systems for this bacterium and the testing of these systems to determine whether E. agglomerans that secrete antimalarial proteins can block the transmission of malaria from mosquitoes to their hosts in a rodent malaria model system. Both Type I and Type II secretion systems will be developed and tested. ? ? ?
