Malaria is a disease caused by protozoan parasites that are transmitted to humans by mosquitoes in the genus Anopheles. There are nearly 220 million new cases of malaria every year, and 500,000 people die from the disease while millions of others are severely debilitated (2016 data). About half the human population is at risk of contracting malaria, and its range may spread as global warming accelerates. The broad, long term objectives of this proposal are to create new methods of combating malaria to complement the current methods of control, namely insecticides to kill mosquito vectors and drugs to kill parasites in infected people. This project seeks to develop the means to create strains of bacteria that can interfere with the ability of mosquitoes to transmit malaria thus reducing its overall health burden and aiding in the goal of eradicating this disease.
The specific aims of this research project are as follows:
Aim 1. Creation of genetically-stable antimalarial strains of Asaia bogorensis For eventual field use, paratransgenic strains of Asaia must be genetically stable. Because these systems cannot be based on laboratory plasmids that use drug selection, we will develop methods to create strains that contain genes that are inserted in the chromosome or are borne on plasmids that require no drug selection and that cannot be horizontally transferred to other bacteria.
Aim 2. Assessing combinations of antimalarial effector genes for effectiveness against Plasmodium. Field strains of Asaia will have to express multiple antiplasmodial effector gene encoding products that act against parasites by different routes to avoid the evolution of resistance by the parasites. We will evaluate different combinations of effector genes in the same strain of Asaia for effectiveness at killing Plasmodium and for their effect on the fitness of the Asaia strains.
Malaria is a global health problem that infects about 250 million people each year. The mainstays of malaria control, insecticides to kill mosquitoes and drugs to treat infected people, are becoming ineffective and must be supplemented with new strategies. This proposal describes approaches to create antiplasmodial bacterial strains that can inhibit the ability of mosquitoes to transmit malaria and thus lower the incidence of the disease. The strains proposed in this grant would be genetically stable and capable of spreading in a wild mosquito population, thus transforming that population from one capable of transmitting malaria to one that could not.
| Shane, Jackie L; Grogan, Christina L; Cwalina, Caroline et al. (2018) Blood meal-induced inhibition of vector-borne disease by transgenic microbiota. Nat Commun 9:4127 |
| Bongio, Nicholas J; Lampe, David J (2015) Inhibition of Plasmodium berghei Development in Mosquitoes by Effector Proteins Secreted from Asaia sp. Bacteria Using a Novel Native Secretion Signal. PLoS One 10:e0143541 |
