Pyrethroids, targeting the voltage gated sodium channel (VGSC), are fundamental for the control of arboviral disease circulation. The spread of pyrethroid resistance among vector species represents thus a major public health concern. Culex pipiens is one of the most abundant European mosquito species and main vector of West Nile virus, leading cause of arboviral encephalitis worldwide. Despite this, monitoring of its resistance status and the understanding of underlying mechanisms are widely neglected. Herein, we performed an oligo-hybridization capture approach on 82 Cx. pipiens specimens from Italy and Greece to investigate the whole coding sequence of the vgsc gene for the presence of known and potential knock-down resistance (kdr) mutations associated with target-site resistance to pyrethroids in insects. Among the 26 non-synonymous substitutions revealed by the analysis, the super-kdr haplotype—i.e. the association of kdr-alleles 918T and 1014F, known for conferring a strongly enhanced resistance phenotype in Musca domestica – was revealed for the first time in mosquitoes. Three more potential kdr alleles were detected for the first time in Cx. pipiens and multiple kdr variants were observed for locus 1014, with allele 1014F, reaching frequencies > 80%. Overall, results depict a worrisome situation that could affect the ability to control West Nile virus outbreaks in southern Europe. To avoid this, resistance monitoring needs to be intensified and an enhancement of the diagnostic tool box for the easy detection of different kdr-variants (including in particular the super-kdr haplotype) and for subsequent functional studies on the resistance phenotype of detected variants, is required.

拟除虫菊酯针对电压门控钠通道 (VGSC)，是控制虫媒病毒疾病循环的基础。因此，拟除虫菊酯抗性在媒介物种中的传播是一个主要的公共卫生问题。淡色库蚊是欧洲数量最多的蚊种之一，也是西尼罗河病毒的主要传播媒介，西尼罗河病毒是全球虫媒病毒性脑炎的主要原因。尽管如此，对其耐药状态的监测和对其潜在机制的理解却被广泛忽视。在此，我们对 82 Cx 进行了寡核苷酸杂交捕获方法。研究人员利用来自意大利和希腊的pipiens标本来研究vgsc基因的整个编码序列，以确定是否存在与昆虫对拟除虫菊酯的靶位点抗性相关的已知和潜在的击倒抗性 ( kdr ) 突变。在分析揭示的 26 个非同义替换中，超级kdr单倍型（即kdr等位基因 918T 和 1014F 的关联，以赋予家蝇强烈增强的抗性表型而闻名）首次在蚊子中被发现。首次在Cx中检测到另外三个潜在的kdr等位基因。 pipiens和多个kdr变异在基因座 1014 上观察到，等位基因 1014F，达到频率 > 80%。总体而言，结果描绘了一种令人担忧的情况，可能会影响南欧控制西尼罗河病毒爆发的能力。 为了避免这种情况，需要加强耐药性监测并增强诊断工具箱，以便轻松检测不同的kdr变异体（特别包括超级kdr单倍型）以及对检测到的变异体的耐药表型进行后续功能研究，是必须的。