Comparative and functional triatomine genomics reveals reductions and expansions in insecticide resistance-related gene families

Abstract

BackgroundTriatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas’ disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. Three enzymatic superfamilies are thought to mediate xenobiotic detoxification and resistance: Glutathione Transferases (GSTs), Cytochromes P450 (CYPs) and Carboxyl/Cholinesterases (CCEs). Improving our knowledge of key triatomine detoxification enzymes will strengthen our understanding of insecticide resistance processes in vectors of Chagas’ disease.Methods and findingsThe discovery and description of detoxification gene superfamilies in normalized transcriptomes of three triatomine species: Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis is presented. Furthermore, a comparative analysis of these superfamilies among the triatomine transcriptomes and the genome of Rhodnius prolixus, also a triatomine vector of Chagas’ disease, and other well-studied insect genomes was performed. The expression pattern of detoxification genes in R. prolixus transcriptomes from key organs was analyzed. The comparisons reveal gene expansions in Sigma class GSTs, CYP3 in CYP superfamily and clade E in CCE superfamily. Moreover, several CYP families identified in these triatomines have not yet been described in other insects. Conversely, several groups of insecticide resistance related enzymes within each enzyme superfamily are reduced or lacking in triatomines. Furthermore, our qRT-PCR results showed an increase in the expression of a CYP4 gene in a T. infestans population resistant to pyrethroids. These results could point to an involvement of metabolic detoxification mechanisms on the high levels of pyrethroid resistance detected in triatomines from the Gran Chaco ecoregion.Conclusions and significanceOur results help to elucidate the potential insecticide resistance mechanisms in vectors of Chagas’ disease and provide new relevant information for this field. This study shows that metabolic resistance might be a contributing cause of the high pyrethroid resistance observed in wild T. infestans populations from the Gran Chaco ecoregion, area in which although subjected to intense pyrethroid treatments, vector control has failed. This study opens new avenues for further functional studies on triatomine detoxification mechanisms.

NovelKdrmutations (K964R and A943V) in pyrethroid‐resistant populations ofTriatoma mazzottiiandTriatoma longipennisfrom Mexico and detoxifying enzymes

“…These data suggest that other mechanisms could be involved in triatomine insecticide resistance. Traverso et al (2017) analyzed the main enzyme superfamilies known to be involved in metabolic insecticide resistance in four important Chagas disease vector species (GST, CYP and CCE). They found that the CYP4 gene analyzed was significantly overexpressed in resistant individuals to pyrethroids.…”

Evolutionary ecology of Chagas disease; what do we know and what do we need?

“…Undoubtedly, triatomine insecticide resistance is a complex and plastic trait as it involves different mechanisms (González Audino, Vassena, Barrios, Zerba, & Picollo, ; Mougabure‐Cueto & Picollo, ; Roca‐Acevedo, Picollo, Capriotti, Sierra, & Santo‐Orihuela, ) with a polygenic determinism (Pessoa et al., ). This trait shall now be investigated through functional genomics approaches (as genuinely initiated by Traverso et al., ), if one is to uncover the true nature of its variations, and propose some mechanistic explanations to the intriguing associations of the highest level of resistance with a specific genetic background and environmental variables (Bustamante Gomez et al., ).…”

Involvement of microRNA miR‐2b‐3p in regulation of metabolic resistance to insecticides in Plutella xylostella

“…Target site modification (alteration as a result of amino acid substitution or mutation) is one mechanism of insecticide resistance in insects and has been reported in both agricultural pests and insect vectors of medical importance (Marcombe et al ., ; Du et al ., ; Ribeiro et al ., ; Sindhu et al ., ). Metabolic resistance to insecticides is another common mechanism, whereby elevated activities of detoxification enzymes such as cytochrome P450s, monooxygenases, carboxylesterases and/or glutathione S‐transferases (GSTs) break down insecticides (Baek et al ., ; Sonoda, ; You et al ., ; Traverso et al ., ).…”