Bacterial symbiosis and paratransgenic control of vector-borne Chagas disease

Abstract

The triatomine vectors of Chagas disease are obligate haematophagous insects, feeding on vertebrate blood throughout their entire developmental cycle. As a result of obtaining their nutrition from a single food source, their diet is devoid of certain vitamins and nutrients. Consequently, these insects harbour populations of bacterial symbionts within their intestinal tract, which provide the required nutrients that are lacking from their diet. We have isolated and characterised symbiont cultures from various triatomine species and developed a method for genetically transforming them. We can then reintroduce them into their original host species, thereby producing stable paratransgenic insects in which we are able to express heterologous gene products. Using this methodology, we have generated paratransgenic Rhodnius prolixus that are refractory for infection with Trypanosoma cruzi. Two examples of potentially refractory genes are currently being expressed in paratransgenic insects. These include the insect immune peptide cecropin A and active single chain antibody fragments. We have also developed an approach that would allow introduction of genetically modified bacterial symbionts into natural populations of Chagas disease vectors. This approach utilises the coprophagic behaviour of these insects, which is the way in which the symbionts are transmitted among bug populations in nature. The production and ultimate release of transgenic or paratransgenic insects for public health applications is potentially very promising but also worthy of much careful consideration with respect to environmental, political, and human safety concerns.

Bacteria of the genus Asaia stably associate with Anopheles stephensi , an Asian malarial mosquito vector

“…There is current interest in the use of microorganisms as biological control agents of vector-borne diseases (6)(7)(8). Microorganisms associated with vectors could exert a direct pathogenic effect on the host (9), interfere with its reproduction (10,11), or reduce vector competence (12,13). Furthermore, the use of genetically modified bacteria to deliver antiparasite molecules has several advantages over the use of genetically modified vectors (14).…”

Facing Malaria Parasite with Mosquito Symbionts

“…R. prolixus harbours in its gut some bacteria that provide nutrients to the insect. These bacteria have been cultivate outside the host, modified to express specific anti-parasite effector molecules and reintroduced within the vector (Beard et al, 2001). These paratransgenic insects have shown to be unable to transmit the parasite.…”

“…A very informative example of advanced studies in genetic manipulation of insect symbionts is Rhodococcus rhodnii, a bacterial symbiont of the reduviid bug Rhodnius prolixus. This bacterium, if manipulated appropriately, can be reintroduced to the vector and inhibit the transmission of Trypanosoma cruzi that causes Chagas disease (Beard et al, 2001). Another example regards the bacterium Alcaligenes, a gut symbiont of the sharpshooter Homalodisca coagulata, the vector of Pierce's crop disease (Bextine et al, 2004).…”

“…These insects harbour populations of bacterial symbionts within their intestinal tract, which provide nutrients that insects do not acquire by the blood source. These symbionts have been isolated, cultured outside the host and genetically transformed to express molecules that render the insect refractory to the infection with Trypanosoma cruzi, the etiological agent of Chagas disease (Beard et al, 2001). Once reintroduced in the vector host, the paratransgenic insect vector showed refractoriness to parasite infection.…”

Secretion of Anti-Plasmodium Effector Proteins from a Natural Pantoea agglomerans Isolate by Using PelB and HlyA Secretion Signals

“…Modifying a resident bacterial species of the mosquito gut to produce effector proteins antagonistic to Plasmodium could prove to be an efficient tool against the spread of Plasmodium to humans during a mosquito blood meal (41). There are several encouraging examples of paratransgenesis used to combat different pathogens in either an insect host or in mammalian cells (2,4,11,40).…”