Malaria vector control in the third millennium: progress and perspectives of molecular approaches

Catteruccia, Flaminia

doi:10.1002/ps.1324

Cited by 43 publications

(32 citation statements)

References 70 publications

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“…At the present time, there is no satisfactory way to completely block malaria transmission, and new approaches are needed (2). To control the transmission of malaria and other vector-borne diseases, diverse new control strategies are being developed for the reduction or elimination of vector populations (3)(4)(5)(6). Toward this aim, the sterile male insect technique provides a safe and efficient strategy that limits the growth of insect pest populations (7).…”

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confidence: 99%

“…In mosquitoes, and more generally in insects, male fertility depends not only on fertile spermatozoa, but also upon secretions transferred to the female during mating to enhance her reproductive success (8,9). A better knowledge of the reproductive biology of A. gambiae, including hormonal regulation of reproduction, would be beneficial, as this could lead to the identification of new target genes for manipulating male and/or female reproductive success (4,5,10).…”

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confidence: 99%

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Anopheles gambiaemales produce and transfer the vitellogenic steroid hormone 20-hydroxyecdysone to females during mating

Pondeville

Maria

Jacques

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

127

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In female insects, the steroid hormone 20-hydroxyecdysone (20E) plays a major role in activating vitellogenesis, a process required for egg development. By contrast with vertebrates, production of large amounts of hormonal steroids has not been reported in adult male insects. In the present study, we analyzed steroidogenesis in both male and female adult of the malaria mosquito Anopheles gambiae and we found that A. gambiae male mosquitoes produce high amounts of the steroid hormone 20E. Importantly, we found that male accessory glands, but not testes, are the source of 20E. Moreover, this steroid hormone is stored in male accessory glands and delivered to females during mating. These findings suggest that male 20E may not act as a true male sex steroid, but more likely as an allohormone. Our results give new insights into speciesspecific physiological processes that govern the reproductive success of the malaria mosquito. This could thus lead to the identification of new target genes for manipulating male and/or female reproductive success, a promising way to reduce or eliminate mosquito population and therefore to control malaria transmission.allohormone ͉ ecdysteroids ͉ malaria ͉ male accessory glands ͉ mosquito

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confidence: 99%

mentioning

confidence: 99%

Anopheles gambiaemales produce and transfer the vitellogenic steroid hormone 20-hydroxyecdysone to females during mating

Pondeville

Maria

Jacques

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

127

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“…Genetic strategies for the population replacement of vector mosquitoes with those that are unable to transmit malaria parasites have recently been proposed as one of the new strategies for malaria control [2,38,39]. Transgenic mosquitoes expressing antimalarial effector molecules, such as a single-chain antibody (scFv) to malaria parasite antigens and antimicrobial peptides, have been reported [6,40–42].…”

Section: Discussionmentioning

confidence: 99%

“…Insecticide resistance has recently been reported in mosquitoes in endemic areas, and, thus, new strategies to control mosquitoes are expected [1]. Population replacement with genetically engineered mosquitoes to block malaria transmission is anticipated to become a new vector control strategy [2,3]. …”

Section: Introductionmentioning

confidence: 99%

Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells

et al. 2016

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Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control.

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“…Vector control strategies based on genetically modified mosquitoes have been advocated for over 15 years to complement existing anti-malaria interventions (reviewed by [4] and [5]). Interventions based on the sterile insect technique (SIT) [6,7] or its transgenic variants, such as the Release of Insects carrying a Dominant Lethal (RIDL) technique deployed in recent years against the dengue vector mosquito Aedes aegypti [8,9,10], are unpractical on the vast geographical scales of malaria transmission.…”

Section: Introductionmentioning

confidence: 99%

Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae

et al. 2017

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Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1) is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes. Using a GFP reporter transgene, we determined that the fat body is the main site of TEP1 expression. We generated transgenic mosquitoes that express TEP1r, a potent refractory allele of TEP1, in the fat body and examined the activity of the transgenic protein in wild-type or TEP1 mutant genetic backgrounds. Transgenic TEP1r rescued loss-of-function mutations, but did not increase parasite resistance in the presence of a wild-type susceptible allele. Consistent with previous reports, TEP1 protein expressed from the transgene in the fat body was taken up by hemocytes upon a challenge with injected bacteria. Furthermore, although maturation of transgenic TEP1 into the cleaved form was impaired in one of the TEP1 mutant lines, it was still sufficient to reduce parasite numbers and induce parasite melanization. We also report here the first use of Transcription Activator Like Effectors (TALEs) in Anopheles gambiae to stimulate expression of endogenous TEP1. We found that artificial elevation of TEP1 expression remains moderate in vivo and that enhancement of endogenous TEP1 expression did not result in increased resistance to Plasmodium. Taken together, our results reveal the difficulty of artificially influencing TEP1-mediated Plasmodium resistance, and contribute to further our understanding of the molecular mechanisms underlying mosquito resistance to Plasmodium parasites.

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Malaria vector control in the third millennium: progress and perspectives of molecular approaches

Cited by 43 publications

References 70 publications

Anopheles gambiaemales produce and transfer the vitellogenic steroid hormone 20-hydroxyecdysone to females during mating

Anopheles gambiaemales produce and transfer the vitellogenic steroid hormone 20-hydroxyecdysone to females during mating

Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells

Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae

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