Cytochrome P450 Genes of the CYP4 Clan and Pyrethroid Resistance in Chagas Disease Vectors

Abstract

Triatomine insects are vectors of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. Although residual pyrethroid spraying has been a successful vector control strategy for many years, a growing number of pyrethroid-resistance foci is being documented, mainly in Triatoma infestans, that led to failures in vector elimination. Insecticide resistance is a multifactorial phenomenon that often implies a combination of three different mechanisms: increased insecticide detoxification, reduced affinity of the site of action, and reduced insecticide penetration through the cuticle. All three mechanisms were reported in pyrethroid-resistant T. infestans. Cytochrome P450s are enzymes involved in the metabolism of xenobiotics and endogenous chemicals. They are encoded by CYP genes and classified into different families and clans. In triatomines, the CYP4 clan is divided in two families, CYP3093 and CYP4, and both exhibit genome-wide, triatomine-specific gene expansions. Some members from each family have been reported to be involved in two of the mechanisms mentioned above, i.e., they participate in insecticide detoxification in different organs and tissues, and in the synthesis of cuticular hydrocarbons, which ultimately can contribute to a reduced insecticide penetration. The aim of this manuscript is to review the current state of knowledge of P450 genes belonging to the CYP4 clan in triatomines and to highlight their potential role in insecticide resistance.

Comparative analysis of detoxification-related gene superfamilies across five hemipteran species

“…CYP4 is the second most numerous CYP clan in the genomes of insects of different orders [ 17 ]. Many genes belonging to this clan have been involved in detoxification [ 19 ]. The analysis revealed 47, 43, 32, 12, and 34 CYP4 genes in R. prolixus , H. halys , N. viridula, C. lectularius, and N. lugens , respectively.…”

A full-length transcriptome and gene expression analysis of three detoxification gene families in a predatory stink bug, Picromerus lewisi

“…Some CYP4 members in insects were also reported to be involved in insecticide resistance and detoxification ( Dulbecco et al, 2022 ). Our observation that 50% (7/14) of CYP4 genes, 80% (4/5) of CYP4H genes and 50% (3/6) of CYP4G genes in P. lewisi were upregulated in the guts, compared to heads, indicated that many CYP4 genes represented by CYP4H and CYP4G subfamilies might also be related to xenobiotic detoxification in P. lewisi .…”

Genetic diversity and Kdr mutations of natural Aedes (Stegomyia) aegypti (Diptera: Culicidae) populations of Brazil

“…Even though the large-scale use of PYs has been restricted, resistance in mosquitoes is still being identified (Macoris et al, 2018). Similarly, resistance to pyrethroids has been reported in other arthropods of public health concern like Triatoma infestans (Klug) (Gaspe et al, 2021;Dulbecco et al, 2022), Lutzomyia longipalpis (Lutz & Neiva) (Alexander et al, 2009), Rhipicephalus microplus (Cossío-Bayúgar et al, 2018;Kumar et al, 2020), and Pediculus humanus capitis (Larkin et al, 2020). In Brazil, resistance to PYs has been reported since the 1990s in mosquitoes and, currently, it continues to be recorded in different areas of the country (da-Cunha et al, 2005;Linss et al, 2014;Valle et al, 2019;Itokawa et al, 2021).…”