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

Author:

Omoke Diana1ORCID,Impoinvil Lucy2,Derilus Dieunel2,Okeyo Stephen1,Saizonou Helga3,Mulder Nicola4,Dada Nsa5,Lenhart Audrey2,Djogbénou Luc6,Ochomo Eric1ORCID

Affiliation:

1. Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR), Kenya

2. Entomology Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, USA

3. University of Abomey Calavi (UAC), Benin

4. Human, Heredity and Health in Africa H3ABionet network, Cape Town, South Africa

5. School of Life Sciences, Arizona State University, Tempe, AZ, USA

6. Tropical Infectious Disease Research Center, University of Abomey- Calavi, Benin

Abstract

Abstract Background 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 in Anopheles arabiensis which is one of the most widespread malaria vectors in the country. We investigated the gene expression profiles of insecticide resistant An. arabiensis populations 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-susceptible An. arabiensis Dongola 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 in An. arabiensis in Western Kenya and suggests that salivary gland proteins and cuticular proteins are associated with resistance to multiple classes of insecticides.

Publisher

Research Square Platform LLC

Reference56 articles.

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3. Balabanidou, V., Kampouraki, A., MacLean, M., Blomquist, G. J., Tittiger, C., Juárez, M. P., Mijailovsky, S. J., Chalepakis, G., Anthousi, A., & Lynd, A. (2016). Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae. Proceedings of the National Academy of Sciences, 113(33), 9268–9273%@ 0027-8424.

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