An expansion of cytochrome P450 genes in triatomines is associated with pyrethroid resistance

SALAMANCA-MORENO JHON; KUMAR SURESH; CALDERÓN FERNÁNDEZ GUSTAVO M; MORICONI DEBORA; PEDRINI NICOLAS; DULBECCO ANDREA B; JUÁREZ M PATRICIA

Congreso; LII Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Residual spray with chemical insecticides has been a successful control strategy of Chagas disease vectors. However, after about 30 years of pyrethroid application resistance foci of Triatoma infestans are increasingly being documented in Argentina and Bolivia. Among genes involved in detoxification processes, cytochrome P450 monooxigenases (CYP) are often associated with relevant roles in metabolic resistance. We have documented an expansion of CYP genes in Rhodnius prolixus genome, specifically into subfamilies CYP4EM (6 genes) and CYP3093A (10 genes). One member of each subfamily-specific expansion were highly expressed (18- and 67-fold induction, respectively) in the integument of deltamethrin-resistant fifth-instar T. infestans nymphs compared with deltamethrin-susceptible specimen. After modeling the molecular docking of deltamethrin to the predicted active sites, the pyrethroid binding was energetically favored for both CYP families in T. infestans but not in R. prolixus. These results suggest that a combination of several mechanisms, i.e. genome-wide gene expansion, induction of gene expression and modification of binding affinity to the active site, might be responsible for the high levels of deltamethrin resistance detected in T. infestans. Ongoing studies of gene silencing will help to understand the mechanisms involved in such resistance.