Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya
Abstract Background The emergence and spread of insecticide resistance in malaria vectors threatens vector control efforts. The use of spatial repellent products (SR) containing volatile insecticides such as transfluthrin offer a promising complementary strategy to current vector control tools. Here...
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2025-06-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-025-11755-y |
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| author | Stephen Okeyo Dieunel Derilus Lucy Mackenzie Impoinvil Nsa Dada Diana Omoke Helga Saizonou Cynthia Awuor Odhiambo Nicola Mulder Gerald Juma Benard W. Kulohoma John E. Gimnig Luc S. Djogbénou Audrey Lenhart Eric Ochomo |
| author_facet | Stephen Okeyo Dieunel Derilus Lucy Mackenzie Impoinvil Nsa Dada Diana Omoke Helga Saizonou Cynthia Awuor Odhiambo Nicola Mulder Gerald Juma Benard W. Kulohoma John E. Gimnig Luc S. Djogbénou Audrey Lenhart Eric Ochomo |
| author_sort | Stephen Okeyo |
| collection | DOAJ |
| description | Abstract Background The emergence and spread of insecticide resistance in malaria vectors threatens vector control efforts. The use of spatial repellent products (SR) containing volatile insecticides such as transfluthrin offer a promising complementary strategy to current vector control tools. Here, we employed whole transcriptome analysis to investigate the molecular mechanisms underlying reduced behavioral sensitivity to transfluthrin in two pyrethroid-resistant populations of Anopheles gambiae s.s. Using a high-throughput screening system (HITSS), we evaluated 600 mosquitoes across three populations (Bungoma field population, the insecticide-resistant Pimperena lab strain, and the susceptible Kisumu lab strain), categorizing them as responders or non-responders based on their SR avoidance behavior. Non-responders exhibited significantly reduced repellency (spatial activity index < 0.1) at standard transfluthrin concentrations (0.0025 μg/ml). Results RNA sequencing of pooled samples (n = 10 mosquitoes per pool, three replicates per condition) revealed distinct transcriptional profiles between responders and non-responders. The cytochrome P450 gene CYP12F12 showed significant overexpression (FC = 36.6389, p < 0.001) in Bungoma non-responders, suggesting its potential role in transfluthrin metabolism. Additionally, we observed population-specific distributions of voltage-gated sodium channel mutations, with fixation of kdr L995F in Pimperena non-responders and elevated frequency (80–100%) of kdr L995S in Bungoma non-responders. Conclusions These findings provide the first molecular evidence linking both metabolic and target-site mechanisms to reduced behavioral sensitivity to transfluthrin in malaria vectors. The co-occurrence of CYP12F12 overexpression and kdr mutations suggests multiple resistance mechanisms may affect spatial repellent efficacy, highlighting the need for resistance monitoring in spatial repellent deployment strategies. Graphical Abstract |
| format | Article |
| id | doaj-art-bb602c84a4bb407bb67768df702c54d1 |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj-art-bb602c84a4bb407bb67768df702c54d12025-08-20T03:25:16ZengBMCBMC Genomics1471-21642025-06-0126111410.1186/s12864-025-11755-yMolecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western KenyaStephen Okeyo0Dieunel Derilus1Lucy Mackenzie Impoinvil2Nsa Dada3Diana Omoke4Helga Saizonou5Cynthia Awuor Odhiambo6Nicola Mulder7Gerald Juma8Benard W. Kulohoma9John E. Gimnig10Luc S. Djogbénou11Audrey Lenhart12Eric Ochomo13Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)Division of Parasitic Diseases and Malaria, Entomology Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionDivision of Parasitic Diseases and Malaria, Entomology Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionTropical Infectious Diseases Research Centre (TIDRC), University of Abomey-Calavi (UAC)Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)Tropical Infectious Diseases Research Centre (TIDRC), University of Abomey-Calavi (UAC)Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)Human, Heredity, and Health in Africa H3A Bionet network, University of Cape Town ZADepartment of Biochemistry, University of NairobiDepartment of Biochemistry, University of NairobiDivision of Parasitic Diseases and Malaria, Entomology Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionTropical Infectious Diseases Research Centre (TIDRC), University of Abomey-Calavi (UAC)Division of Parasitic Diseases and Malaria, Entomology Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionKenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)Abstract Background The emergence and spread of insecticide resistance in malaria vectors threatens vector control efforts. The use of spatial repellent products (SR) containing volatile insecticides such as transfluthrin offer a promising complementary strategy to current vector control tools. Here, we employed whole transcriptome analysis to investigate the molecular mechanisms underlying reduced behavioral sensitivity to transfluthrin in two pyrethroid-resistant populations of Anopheles gambiae s.s. Using a high-throughput screening system (HITSS), we evaluated 600 mosquitoes across three populations (Bungoma field population, the insecticide-resistant Pimperena lab strain, and the susceptible Kisumu lab strain), categorizing them as responders or non-responders based on their SR avoidance behavior. Non-responders exhibited significantly reduced repellency (spatial activity index < 0.1) at standard transfluthrin concentrations (0.0025 μg/ml). Results RNA sequencing of pooled samples (n = 10 mosquitoes per pool, three replicates per condition) revealed distinct transcriptional profiles between responders and non-responders. The cytochrome P450 gene CYP12F12 showed significant overexpression (FC = 36.6389, p < 0.001) in Bungoma non-responders, suggesting its potential role in transfluthrin metabolism. Additionally, we observed population-specific distributions of voltage-gated sodium channel mutations, with fixation of kdr L995F in Pimperena non-responders and elevated frequency (80–100%) of kdr L995S in Bungoma non-responders. Conclusions These findings provide the first molecular evidence linking both metabolic and target-site mechanisms to reduced behavioral sensitivity to transfluthrin in malaria vectors. The co-occurrence of CYP12F12 overexpression and kdr mutations suggests multiple resistance mechanisms may affect spatial repellent efficacy, highlighting the need for resistance monitoring in spatial repellent deployment strategies. Graphical Abstracthttps://doi.org/10.1186/s12864-025-11755-yAn. gambiae s.sTransfluthrinInsecticide resistanceSpatial repellentsRNA-seqCYP12 F12 |
| spellingShingle | Stephen Okeyo Dieunel Derilus Lucy Mackenzie Impoinvil Nsa Dada Diana Omoke Helga Saizonou Cynthia Awuor Odhiambo Nicola Mulder Gerald Juma Benard W. Kulohoma John E. Gimnig Luc S. Djogbénou Audrey Lenhart Eric Ochomo Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya BMC Genomics An. gambiae s.s Transfluthrin Insecticide resistance Spatial repellents RNA-seq CYP12 F12 |
| title | Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya |
| title_full | Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya |
| title_fullStr | Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya |
| title_full_unstemmed | Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya |
| title_short | Molecular markers of reduced behavioral sensitivity to transfluthrin in Anopheles gambiae s.s. from Western Kenya |
| title_sort | molecular markers of reduced behavioral sensitivity to transfluthrin in anopheles gambiae s s from western kenya |
| topic | An. gambiae s.s Transfluthrin Insecticide resistance Spatial repellents RNA-seq CYP12 F12 |
| url | https://doi.org/10.1186/s12864-025-11755-y |
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