Abstract
Deltamethrin (DM) insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6) is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.
Highlights
Mosquito-borne diseases, such as malaria, dengue fever, yellow fever, filariasis and encephalitis, cause severe mortality and morbidity around the world, and pose significant threats to public health [1,2,3,4]
Widespread and improper use of insecticides has induced the development of insecticide resistance [10,11], which has become the main obstacle for the mosquito-borne disease management [12,13,14]
A global comparative proteomic analysis was performed between DM-susceptible and -resistant mosquito cells
Summary
Mosquito-borne diseases, such as malaria, dengue fever, yellow fever, filariasis and encephalitis, cause severe mortality and morbidity around the world, and pose significant threats to public health [1,2,3,4]. For a long period of time, insecticides have been the primary method for managing mosquito-borne diseases [5,6]. Widespread and improper use of insecticides has induced the development of insecticide resistance [10,11], which has become the main obstacle for the mosquito-borne disease management [12,13,14]. Insecticide resistance is polygenic inheritance phenomenon, which suggests that multiple genes are associated with resistance [15]. Large-scale transcriptional gene expression profiling based on suppression subtractive hybridization (SSH) and cDNA microarray studies had been carried out to identify DM resistance-associated genes in Culex pipiens pallens [16,17]. Novel genes associated with DM resistance have been identified, the mechanisms underlying DM resistance are still not fully understood. Characterization and comparison of the protein profiles of susceptible and resistant strains will provide valuable information regarding the resistance mechanisms in mosquitoes
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