Abstract
BACKGROUND: Cyphenothrin, a type II synthetic pyrethroid, is widely recommended by the World Health Organization (WHO) for control programs for mosquitoes such as Culex quinquefasciatus. This cosmopolitan mosquito species plays a pivotal role in transmitting several neglected tropical diseases, including lymphatic filariasis, West Nile virus, Japanese encephalitis, and so on. Besides treatment, vector control programs heavily rely on insecticides, leading to varying resistance due to prolonged exposure. METHODS: The present study assessed the susceptibility status of field-collected Cx. quinquefasciatus larvae from two filarial endemic districts of sub-Himalayan West Bengal against cyphenothrin. All the wild populations have been exposed to their respective lethal concentration doses. Monooxygenase levels and carboxylesterase activities were quantified both in the wild and cyphenothrin-exposed populations. The expression profiles of selected carboxylesterase (esterase A and esterase B) and CYP450 (CYP6AA7, CYP9J40, and CYP9J45) genes were also assessed. Molecular docking analyses were performed to evaluate the binding affinities and interaction mechanisms of cyphenothrin with the selected proteins. RESULTS: Most of the populations showed elevated resistance status to cyphenothrin. In enzymatic assays, elevated levels of monooxygenases and carboxylesterases are found both in the wild and cyphenothrin-exposed populations. The expression profiles of selected CYP450s and carboxylesterase genes indicated an upregulation in the studied wild and exposed populations. Furthermore, molecular docking simulations corroborated the strong binding affinities of cyphenothrin to these detoxification enzymes. CONCLUSIONS: These findings suggest the involvement of a few detoxifying genes in resistance development against cyphenothrin in Cx. quinquefasciatus mosquitoes and advocates the urgent need for regular resistance monitoring, molecular surveillance, gene knockdown studies, and incorporation of synergists into integrated vector management frameworks to sustain effectiveness of mosquito control programs.