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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.
Okeyo et al. (Thu,) studied this question.