Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae
Abstract Background The widespread use of pyrethroid insecticides in Africa has led to the development of strong resistance in Anopheles mosquitoes. Introducing new active ingredients can contribute to overcome this phenomenon and ensure the effectiveness of vector control strategies. Transfluthrin...
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| Format: | Article |
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BMC
2023-09-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-023-04673-5 |
| _version_ | 1797453833875488768 |
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| author | Marius Gonse Zoh Jean-Marc Bonneville Frederic Laporte Jordan Tutagata Christabelle G. Sadia Behi K. Fodjo Chouaibou S. Mouhamadou Justin McBeath Frederic Schmitt Sebastian Horstmann Stéphane Reynaud Jean-Philippe David |
| author_facet | Marius Gonse Zoh Jean-Marc Bonneville Frederic Laporte Jordan Tutagata Christabelle G. Sadia Behi K. Fodjo Chouaibou S. Mouhamadou Justin McBeath Frederic Schmitt Sebastian Horstmann Stéphane Reynaud Jean-Philippe David |
| author_sort | Marius Gonse Zoh |
| collection | DOAJ |
| description | Abstract Background The widespread use of pyrethroid insecticides in Africa has led to the development of strong resistance in Anopheles mosquitoes. Introducing new active ingredients can contribute to overcome this phenomenon and ensure the effectiveness of vector control strategies. Transfluthrin is a polyfluorinated pyrethroid whose structural conformation was thought to prevent its metabolism by cytochrome P450 monooxygenases in malaria vectors, thus representing a potential alternative for managing P450-mediated resistance occurring in the field. In this study, a controlled selection was used to compare the dynamics of resistance between transfluthrin and the widely used pyrethroid deltamethrin in the mosquito Anopheles gambiae. Then, the associated molecular mechanisms were investigated using target-site mutation genotyping and RNA-seq. Methods A field-derived line of An. gambiae carrying resistance alleles at low frequencies was used as starting material for a controlled selection experiment. Adult females were selected across 33 generations with deltamethrin or transfluthrin, resulting in three distinct lines: the Delta-R line (selected with deltamethrin), the Transflu-R line (selected with transfluthrin) and the Tiassale-S line (maintained without selection). Deltamethrin and transfluthrin resistance levels were monitored in each selected line throughout the selection process, as well as the frequency of the L1014F kdr mutation. At generation 17, cross-resistance to other public health insecticides was investigated and transcriptomes were sequenced to compare gene transcription variations and polymorphisms associated with adaptation to each insecticide. Results A rapid increase in resistance to deltamethrin and transfluthrin was observed throughout the selection process in each selected line in association with an increased frequency of the L1014F kdr mutation. Transcriptomic data support a broader response to transfluthrin selection as compared to deltamethrin selection. For instance, multiple detoxification enzymes and cuticle proteins were specifically over-transcribed in the Transflu-R line including the known pyrethroid metabolizers CYP6M2, CYP9K1 and CYP6AA1 together with other genes previously associated with resistance in An. gambiae. Conclusion This study confirms that recurrent exposure of adult mosquitoes to pyrethroids in a public health context can rapidly select for various resistance mechanisms. In particular, it indicates that in addition to target site mutations, the polyfluorinated pyrethroid transfluthrin can select for a broad metabolic response, which includes some P450s previously associated to resistance to classical pyrethroids. This unexpected finding highlights the need for an in-depth study on the adaptive response of mosquitoes to newly introduced active ingredients in order to effectively guide and support decision-making programmes in malaria control. |
| first_indexed | 2024-03-09T15:28:35Z |
| format | Article |
| id | doaj.art-c271951ea22e424c9e9dc965f0974f0a |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-03-09T15:28:35Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-c271951ea22e424c9e9dc965f0974f0a2023-11-26T12:24:24ZengBMCMalaria Journal1475-28752023-09-0122111310.1186/s12936-023-04673-5Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiaeMarius Gonse Zoh0Jean-Marc Bonneville1Frederic Laporte2Jordan Tutagata3Christabelle G. Sadia4Behi K. Fodjo5Chouaibou S. Mouhamadou6Justin McBeath7Frederic Schmitt8Sebastian Horstmann9Stéphane Reynaud10Jean-Philippe David11Laboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSLaboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSLaboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSLaboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSCentre Suisse de Recherches ScientifiquesCentre Suisse de Recherches ScientifiquesCentre Suisse de Recherches ScientifiquesEnvu, Milton HallEnvu, 2022 Environmental Science FR S.A.SEnvu, 2022 ES Deutschland GmbHLaboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSLaboratoire d’Ecologie Alpine (LECA), Grenoble-Alpes University, Savoie Mont-Blanc University, CNRSAbstract Background The widespread use of pyrethroid insecticides in Africa has led to the development of strong resistance in Anopheles mosquitoes. Introducing new active ingredients can contribute to overcome this phenomenon and ensure the effectiveness of vector control strategies. Transfluthrin is a polyfluorinated pyrethroid whose structural conformation was thought to prevent its metabolism by cytochrome P450 monooxygenases in malaria vectors, thus representing a potential alternative for managing P450-mediated resistance occurring in the field. In this study, a controlled selection was used to compare the dynamics of resistance between transfluthrin and the widely used pyrethroid deltamethrin in the mosquito Anopheles gambiae. Then, the associated molecular mechanisms were investigated using target-site mutation genotyping and RNA-seq. Methods A field-derived line of An. gambiae carrying resistance alleles at low frequencies was used as starting material for a controlled selection experiment. Adult females were selected across 33 generations with deltamethrin or transfluthrin, resulting in three distinct lines: the Delta-R line (selected with deltamethrin), the Transflu-R line (selected with transfluthrin) and the Tiassale-S line (maintained without selection). Deltamethrin and transfluthrin resistance levels were monitored in each selected line throughout the selection process, as well as the frequency of the L1014F kdr mutation. At generation 17, cross-resistance to other public health insecticides was investigated and transcriptomes were sequenced to compare gene transcription variations and polymorphisms associated with adaptation to each insecticide. Results A rapid increase in resistance to deltamethrin and transfluthrin was observed throughout the selection process in each selected line in association with an increased frequency of the L1014F kdr mutation. Transcriptomic data support a broader response to transfluthrin selection as compared to deltamethrin selection. For instance, multiple detoxification enzymes and cuticle proteins were specifically over-transcribed in the Transflu-R line including the known pyrethroid metabolizers CYP6M2, CYP9K1 and CYP6AA1 together with other genes previously associated with resistance in An. gambiae. Conclusion This study confirms that recurrent exposure of adult mosquitoes to pyrethroids in a public health context can rapidly select for various resistance mechanisms. In particular, it indicates that in addition to target site mutations, the polyfluorinated pyrethroid transfluthrin can select for a broad metabolic response, which includes some P450s previously associated to resistance to classical pyrethroids. This unexpected finding highlights the need for an in-depth study on the adaptive response of mosquitoes to newly introduced active ingredients in order to effectively guide and support decision-making programmes in malaria control.https://doi.org/10.1186/s12936-023-04673-5An. gambiaeTransfluthrinDeltamethrinMetabolic resistanceTranscriptomics |
| spellingShingle | Marius Gonse Zoh Jean-Marc Bonneville Frederic Laporte Jordan Tutagata Christabelle G. Sadia Behi K. Fodjo Chouaibou S. Mouhamadou Justin McBeath Frederic Schmitt Sebastian Horstmann Stéphane Reynaud Jean-Philippe David Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae Malaria Journal An. gambiae Transfluthrin Deltamethrin Metabolic resistance Transcriptomics |
| title | Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae |
| title_full | Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae |
| title_fullStr | Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae |
| title_full_unstemmed | Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae |
| title_short | Deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector Anopheles gambiae |
| title_sort | deltamethrin and transfluthrin select for distinct transcriptomic responses in the malaria vector anopheles gambiae |
| topic | An. gambiae Transfluthrin Deltamethrin Metabolic resistance Transcriptomics |
| url | https://doi.org/10.1186/s12936-023-04673-5 |
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