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Gene silencing through RNAi and antisense Vivo-Morpholino increases the efficacy of pyrethroids on larvae of Anopheles stephensi.
Negri, Agata; Ferrari, Marco; Nodari, Riccardo; Coppa, Edoardo; Mastrantonio, Valentina; Zanzani, Sergio; Porretta, Daniele; Bandi, Claudio; Urbanelli, Sandra; Epis, Sara.
Afiliación
  • Negri A; Department of Environmental Biology, Sapienza University of Rome, Via dei Sardi 70, 00185, Rome, Italy.
  • Ferrari M; Department of Biosciences and Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", University of Milan, Via Celoria 26, 20133, Milan, Italy.
  • Nodari R; Centro Interuniversitario di Ricerca sulla Malaria/Italian Malaria Network, Via del Giochetto, 06126, Perugia, Italy.
  • Coppa E; Department of Biosciences and Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", University of Milan, Via Celoria 26, 20133, Milan, Italy.
  • Mastrantonio V; Texas Biomedical Research Institute, San Antonio, 7620 NW Loop 410, San Antonio, TX, 78227-5301, USA.
  • Zanzani S; Department of Biosciences and Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", University of Milan, Via Celoria 26, 20133, Milan, Italy.
  • Porretta D; Centro Interuniversitario di Ricerca sulla Malaria/Italian Malaria Network, Via del Giochetto, 06126, Perugia, Italy.
  • Bandi C; Department of Biosciences and Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", University of Milan, Via Celoria 26, 20133, Milan, Italy.
  • Urbanelli S; Department of Environmental Biology, Sapienza University of Rome, Via dei Sardi 70, 00185, Rome, Italy.
  • Epis S; Department of Veterinary Medicine-DIMEVET, Università degli Studi di Milano, Via Celoria, 10, 20133, Milan, Italy.
Malar J ; 18(1): 294, 2019 Aug 28.
Article en En | MEDLINE | ID: mdl-31462239
ABSTRACT

BACKGROUND:

Insecticides are still at the core of insect pest and vector control programmes. Several lines of evidence indicate that ABC transporters are involved in detoxification processes against insecticides, including permethrin and other pyrethroids. In particular, the ABCG4 gene, a member of the G subfamily, has consistently been shown to be up-regulated in response to insecticide treatments in the mosquito malaria vector Anopheles stephensi (both adults and larvae).

METHODS:

To verify the actual involvement of this transmembrane protein in the detoxification process of permethrin, bioassays on larvae of An. stephensi, combining the insecticide with a siRNA, specifically designed for the inhibition of ABCG4 gene expression were performed. Administration to larvae of the same siRNA, labeled with a fluorescent molecule, was effected to investigate the systemic distribution of the inhibitory RNA into the larval bodies. Based on siRNA results, similar experiments using antisense Vivo-Morpholinos (Vivo-MOs) were effected. These molecules, compared to siRNA, are expected to guarantee a higher stability in environmental conditions and in the insect gut, and present thus a higher potential for future in-field applications.

RESULTS:

Bioassays using two different concentrations of siRNA, associated with permethrin, led to an increase of larval mortality, compared with results with permethrin alone. These outcomes confirm that ABCG4 transporter plays a role in the detoxification process against the selected insecticide. Moreover, after fluorescent labelling, it was shown the systemic dissemination of siRNA in different body districts of An. stephensi larvae, which suggest a potential systemic effect of the molecule. At the same time, results of Vivo-MO experiments were congruent with those obtained using siRNA, thus confirming the potential of ABCG4 inhibition as a strategy to increase permethrin susceptibility in mosquitoes. For the first time, Vivo-MOs were administered in water to larvae, with evidence for a biological effect.

CONCLUSIONS:

Targeting ABCG4 gene for silencing through both techniques resulted in an increased pyrethroid efficacy. These results open the way toward the possibility to exploit ABCG4 inhibition in the context of integrated programmes for the control An. stephensi mosquitoes and malaria transmission.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piretrinas / Resistencia a los Insecticidas / ARN sin Sentido / Morfolinos / Insecticidas / Anopheles Límite: Animals Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2019 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piretrinas / Resistencia a los Insecticidas / ARN sin Sentido / Morfolinos / Insecticidas / Anopheles Límite: Animals Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2019 Tipo del documento: Article País de afiliación: Italia