In the past decade, national and international efforts to control and eradicate malaria allowed to reduce the number of cases and deaths worldwide. Control programs mostly rely on vector control through the use of insecticides and personal protection, employing repellents and insecticide treated bed nets. According to WHO, despite these efforts and the encouraging results achieved, 212 million cases and more than 400000 deaths still occurred in 2015. Insecticide efficacy is threatened by the insurgence of resistance mechanisms in vector mosquitoes all around the world, representing an increasing danger for people living in endemic areas. Anopheles stephensi, vector of the pathogen Plasmodium, is one of the three anopheline species responsible for malaria transmission in the south of Asia. To understand molecular and regulatory mechanisms of insecticide action, we performed a transcriptomic analysis on larvae of An. stephensi exposed for 6, 24 and 48 hours to a LD50 of permethrin, one of the most used insecticides for vector control. We created a dataset of gene families relevant in the response to toxicants such as P450, ABC-transporters, cuticular genes, glutathione S-transferase and carboxylesterases, both characterizing sequences de novo and employing already annotated sequences from the literature. ABC-transporters confirmed their major role in detoxification in insects and their potential as target for novel control strategies. Indeed, our analysis allowed us to identify ABCG4, a highly expressed ABC-transporter, as a target for the gene silencing through RNA interference (RNAi) with the goal to increase insecticide efficacy. We performed bioassays on larvae of An. stephensi exposed to a LD50 of permethrin alone and in combination with siRNAs for 6 and 24 hours. The increased mortality in siRNA treated larvae confirms the role of ABC-G4 in insecticide detoxification and the potential of RNAi for vector control.

Temporal patterns of insecticide response in Anopheles stephensi and identification of molecular targets for gene silencing / M. Ferrari, L.D. Marco, D. Porretta, V. Mastrantonio, A. Negri, S. Urbanelli, G. Favia, D. Sassera, C. Bandi, S. Epis. ((Intervento presentato al convegno Annual meeting of the Italian Malaria Network tenutosi a Roma nel 2017.

Temporal patterns of insecticide response in Anopheles stephensi and identification of molecular targets for gene silencing

M. Ferrari
Primo
;
D. Sassera;C. Bandi
Penultimo
;
S. Epis
Ultimo
2017

Abstract

In the past decade, national and international efforts to control and eradicate malaria allowed to reduce the number of cases and deaths worldwide. Control programs mostly rely on vector control through the use of insecticides and personal protection, employing repellents and insecticide treated bed nets. According to WHO, despite these efforts and the encouraging results achieved, 212 million cases and more than 400000 deaths still occurred in 2015. Insecticide efficacy is threatened by the insurgence of resistance mechanisms in vector mosquitoes all around the world, representing an increasing danger for people living in endemic areas. Anopheles stephensi, vector of the pathogen Plasmodium, is one of the three anopheline species responsible for malaria transmission in the south of Asia. To understand molecular and regulatory mechanisms of insecticide action, we performed a transcriptomic analysis on larvae of An. stephensi exposed for 6, 24 and 48 hours to a LD50 of permethrin, one of the most used insecticides for vector control. We created a dataset of gene families relevant in the response to toxicants such as P450, ABC-transporters, cuticular genes, glutathione S-transferase and carboxylesterases, both characterizing sequences de novo and employing already annotated sequences from the literature. ABC-transporters confirmed their major role in detoxification in insects and their potential as target for novel control strategies. Indeed, our analysis allowed us to identify ABCG4, a highly expressed ABC-transporter, as a target for the gene silencing through RNA interference (RNAi) with the goal to increase insecticide efficacy. We performed bioassays on larvae of An. stephensi exposed to a LD50 of permethrin alone and in combination with siRNAs for 6 and 24 hours. The increased mortality in siRNA treated larvae confirms the role of ABC-G4 in insecticide detoxification and the potential of RNAi for vector control.
gen-2017
Settore BIO/11 - Biologia Molecolare
Settore VET/06 - Parassitologia e Malattie Parassitarie degli Animali
Temporal patterns of insecticide response in Anopheles stephensi and identification of molecular targets for gene silencing / M. Ferrari, L.D. Marco, D. Porretta, V. Mastrantonio, A. Negri, S. Urbanelli, G. Favia, D. Sassera, C. Bandi, S. Epis. ((Intervento presentato al convegno Annual meeting of the Italian Malaria Network tenutosi a Roma nel 2017.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/474141
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