Okeyo Stephen, Derilus Dieunel, Impoinvil Lucy Mackenzie, Dada Nsa, Omoke Diana, Saizonou Helga, Odhiambo Cynthia Awuor, Mulder Nicola, Juma Gerald, Kulohoma Benard W, Gimnig John E, Djogbénou Luc S, Lenhart Audrey, Ochomo Eric
Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR), Kisumu, Kenya.
Department of Biochemistry, University of Nairobi, Nairobi, Kenya.
BMC Genomics. 2025 Jun 5;26(1):565. doi: 10.1186/s12864-025-11755-y.
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).
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.
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.
疟疾病媒中杀虫剂抗性的出现和传播威胁着病媒控制工作。使用含有诸如四氟甲醚菊酯等挥发性杀虫剂的空间驱避产品（SR）为当前的病媒控制工具提供了一种有前景的补充策略。在此，我们采用全转录组分析来研究冈比亚按蚊两个拟除虫菊酯抗性种群对四氟甲醚菊酯行为敏感性降低的分子机制。使用高通量筛选系统（HITSS），我们评估了三个种群（邦戈马野外种群、抗杀虫剂的平佩雷纳实验室品系和敏感的基苏木实验室品系）中的600只蚊子，并根据它们的SR回避行为将其分类为反应者或无反应者。在标准四氟甲醚菊酯浓度（0.0025μg/ml）下，无反应者表现出显著降低的驱避性（空间活动指数<0.1）。
对混合样本（每个样本池10只蚊子，每个条件三个重复）进行RNA测序，揭示了反应者和无反应者之间不同的转录谱。细胞色素P450基因CYP12F12在邦戈马无反应者中显示出显著过表达（FC = 36.6389，p < 0.001），表明其在四氟甲醚菊酯代谢中的潜在作用。此外，我们观察到电压门控钠通道突变的种群特异性分布，平佩雷纳无反应者中kdr L995F固定，邦戈马无反应者中kdr L995S频率升高（80 - 100%）。
这些发现提供了首个分子证据，将代谢和靶位点机制与疟疾病媒对四氟甲醚菊酯行为敏感性降低联系起来。CYP12F12过表达和kdr突变的同时出现表明多种抗性机制可能影响空间驱避效果，突出了在空间驱避部署策略中进行抗性监测的必要性。
