Paratransgenic Control of Vector Borne Diseases

Abstract

Conventional methodologies to control vector borne diseases with chemical pesticides are often associated with environmental toxicity, adverse effects on human health and the emergence of insect resistance. In the paratransgenic strategy, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases the host's ability to transmit the pathogen. We have successfully utilized this strategy to reduce carriage rates of Trypanosoma cruzi, the causative agent of Chagas disease, in the triatomine bug, Rhodnius prolixus, and are currently developing this methodology to control the transmission of Leishmania donovani by the sand fly Phlebotomus argentipes. Several effector molecules, including antimicrobial peptides and highly specific single chain antibodies, are currently being explored for their anti-parasite activities in these two systems. In preparation for eventual field use, we are actively engaged in risk assessment studies addressing the issue of horizontal gene transfer from the modified bacteria to environmental microbes.

Differential Pattern of Infection of Sylvatic Nymphs and Domiciliary Adults of Triatoma infestans with Trypanosoma cruzi Genotypes in Chile

“…14,23,51 We cannot discard the route of direct transmission between triatomines by coprophagy or cannibalism, 25,[52][53][54] given that all triatomines must obtain their symbionts at least once in their lifetime, probably by coprophagy. 25,55 Most of the time, field insects are starving, which enhances their cannibalistic behavior towards other triatomines that were able to feed, probably acquiring T. cruzi in the process, in case that the engorged insect was infected. 53 We report high infection rates with T. cruzi in adults found in sylvatic and domiciliary habitats, and lower levels of infection among the nymphal instars found in the sylvatic foci.…”

Dynamics of Mosquitoes Populations with Different Strategies for Releasing Sterile Mosquitoes

“…The paratransgenesis strategy is to introduce genes into bacteria of the mosquito midgut, instead of into the mosquito itself, and to genetically modify the bacteria, whose products also inhibit parasite development. Both of these techniques aim to replace the wild mosquitoes by disease resistant mosquitoes [8,14,22,25].…”

Symbiotic control of mosquito borne disease

“…9 Moreover, semi-field trials have demonstrated the controlled spread of genetically modified symbionts in natural populations of triatominae vectors, thus reinforcing the feasibility of paratransgenesis as part of an integrated vector control program. 10,11 These achievements in insect vectors other than mosquito have strongly encouraged researchers to develop similar approaches to control MBD.…”