Whole transcriptomic analysis reveals overexpression of salivary gland and cuticular proteins genes in insecticide-resistant Anopheles arabiensis from Western Kenya.

AbstractBackground Effective vector control is key to malaria prevention. However, this is now compromised by increased insecticide resistance due to continued reliance on insecticide-based control interventions. In Kenya, we have observed heterogenous resistance to pyrethroids and organophosphates inAnopheles arabiensiswhich is one of the most widespread malaria vectors in the country. We investigated the gene expression profiles of insecticide resistantAn. arabiensispopulations from Migori and Siaya counties in Western Kenya using RNA-Sequencing. CDC bottle assays were conducted using deltamethrin (DELTA), alphacypermethrin (ACYP) and pirimiphos-methyl (PMM) to determine the resistance status in both sites. Results Mosquitoes from Migori had average mortalities of 91%, 92% and 58% while those from Siaya had 85%, 86%, and 30% when exposed to DELTA, ACYP and PMM, respectively. RNA-Seq analysis was done on pools of mosquitoes which survived exposure (‘resistant’), mosquitoes that were not exposed, and the insecticide-susceptibleAn. arabiensisDongola strain. Gene expression profiles of resistant mosquitoes from both Migori and Siaya showed an overexpression mainly of salivary gland proteins belonging to both the short and long form D7 genes, and cuticular proteins (including CPR9, CPR10, CPR15, CPR16). Additionally, the overexpression of detoxification genes including cytochrome P450s (CYP9M1, CYP325H1, CYP4C27, CYP9L1 and CYP307A1), 2 carboxylesterases and a glutathione-s-transferase (GSTE4) were also shared between DELTA, ACYP, and PMM survivors, pointing to potential contribution to cross resistance to both pyrethroid and organophosphate insecticides. Conclusion This study provides novel insights into the molecular basis of insecticide resistance inAn. arabiensisin Western Kenya and suggests that salivary gland proteins and cuticular proteins are associated with resistance to multiple classes of insecticides.