KNOCKDOWN OF THE CYTOCHROME P450 CYP4PR1 IN PYRETHROID-RESISTANT TRIATOMA INFESTANS INCREASES SUSCEPTIBILITY TO DELTAMETHRIN.

DULBECCO, A. B.; PEDRINI, N.; MORICONI, D. E.

Congreso; SAIB-SAMIGE; 2020

Insect resistance to chemical pesticides often implies a combination of three different mechanisms: increased detoxification, reduced affinity of the site of action, and reduced penetration through the cuticle. The insect integument is known to participate as the cuticular penetration factor of resistance, but recently this tissue was also linked with metabolic resistance due to P450-dependent detoxification in the Chagas disease vector Triatoma infestans. Metabolic resistance to chemical insecticides implies a greater capacity to detoxify insecticides due to an increase in the expression of genes and/or in the activity of enzymes related to detoxification metabolism. The cytochrome P450 monooxygenases (CYP) constitute one of the largest superfamilies of enzymes found in nature. In insects, all CYP genes described are assigned to one of four clans: CYP2, CYP3, CYP4 and the mitochondrial CYP clan. Both mitochondrial and CYP2 clans are associated with core functions in development and physiology, whereas CYP3 and CYP4 clans are associated with environmental interactions and play a key role in detoxification of chemical insecticides. In this study, we identified, named and classified all P450s known to date in T. infestans. One of them, CYP4PR1, represents the first member of a new cytochrome P450 subfamily from the clan CYP4 in insects. We found that CYP4PR1 is expressed almost exclusively in the integument tissue, and it was significantly overexpressed in pyrethroid-resistant compared to pyrethroid-susceptible nymphs. The knockdown of CYP4PR1 by RNA interference in pyrethroid-resistant nymphs caused a significant increment in insect mortality after topical application of two different doses of deltamethrin. Taken together, these results support the role of the integument on metabolic resistance and suggest that CYP4PR1 might contribute to resistance in integument tissue of T. infestans.