Knockdown of CYP4PR1, a cytochrome P450 gene highly expressed in the integument tissue of Triatoma infestans, increases susceptibility to deltamethrin in pyrethroid-resistant insects

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 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. The objectives of this study were i) to name and classify all P450s known to date in T. infestans, ii) to characterise one of them, CYP4PR1, representing the first member of a new cytochrome P450 subfamily described in insects, and iii) to investigate the potential role of CYP4PR1 in metabolic resistance to deltamethrin in T. infestans. We found that CYP4PR1 is expressed almost exclusively in the integument tissue, and its expression was not induced by deltamethrin. 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. 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.