Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly

Abstract

Background The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides. Methods By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displaying condition-specific polymorphisms, as well as those differentially expressed. Results Both analyses revealed that resistant individuals have altered expression and allele-specific expression of genes involved in proteolysis (specifically serine-endopeptidase), olfactory perception and cuticle metabolism, among others. We also confirmed that resistant individuals carry almost invariably the Trp251Ser mutation in the esterase E3, known to confer OP and Pyrethroid resistance. Interestingly, genes involved in metabolic and detoxifying processes (notably cytochrome P450s) were found under-expressed in resistant individuals. An exception to this were esterases, which were found up-regulated. Conclusions These observations suggest that reduced penetration and aversion to dimethyl-OP contaminated food may be important complementary strategies of resistant individuals. The specific genes and processes found are an important starting point for future functional studies. Their role in insecticide resistance merits consideration to better the current pest management strategies.

Experimental evolution of insect resistance to two pesticide classes reveals mechanistic diversity and context-dependent fitness costs

“…Organophosphate resistance has been most widely associated with acetylcholinesterase (AChE) copy number variation or target-site modifications and metabolic detoxification by carboxyl ester hydrolases (CEHs) and other esterases (Alon et al, 2008;Carletto et al, 2010;Carvalho et al, 2013;Coates et al, 2016;Haubruge et al, 2002;Kwon et al, 2010). Differential expression of cytochrome P450s, glutathione S-transferases (GSTs), short-chain dehydrogenases/reductases (SDRs), serineendopeptidases, and cuticular genes have also been described in organophosphate resistant insect populations (Carvalho et al, 2013;Saavedra-Rodriguez et al, 2014;Tandonnet et al, 2020;Zhu et al, 2012). In particular, other studies examining population variation in organophosphate resistance mechanisms have found common differential activity of esterases (Reyes et al, 2015) and GSTs (Saavedra-Rodriguez et al, 2014).…”

“…In congruence with past evidence for the importance of P450s in pyrethroid resistance (Scott et al, 2015;Yan et al, 2018), all three Pyrregime populations commonly constitutively downregulated four cytochrome P450 genes (6BQ11, 6BQ7, 345A1, 6BQ10). While pesticide resistance is often associated with the overexpression of P450s, other studies have observed the downregulation of P450s in insecticide resistant populations (David et al, 2014;Tandonnet et al, 2020;Yang and Liu, 2011). Decreased expression of specific P450s might reduce the metabolism of compounds into more active or damaging forms or be involved in controlling inflammatory responses (Feyereisen, 2019;Wang et al, 2017).…”

“…Based on previous studies investigating molecular mechanisms of organophosphate resistance, we expected common differential expression of detoxification genes including cytochrome P450s, carboxyl ester hydrolases (CEHs), esterases, and glutathione S-transferases (GSTs) among OP-regime populations (Boyer et al, 2012;Meinke et al, 2021;Oakeshott et al, 2013;Pavlidi et al, 2018;Sogorb and Vilanova, 2002;Tandonnet et al, 2020). However, after organophosphate selection, each population tended to differentially express different P450, GST, and UGT genes canonically associated with detoxification (Figs.…”

“…5, 7A). Changes in cuticular metabolism can also aid in pesticide resistance (Balabanidou et al, 2018;Tandonnet et al, 2020), and Coffee, in particular, constitutively upregulated several cuticular proteins in response to organophosphate selection (Figs. 5, 8A).…”

“…Organophosphates and pyrethroids are mainly detoxified through oxidation and hydrolysis, and resistance associated with differential expression of diverse canonical detoxification genes has been described for both pesticide types (Boyer et al, 2012;Meinke et al, 2021;Oakeshott et al, 2013;Pavlidi et al, 2018;Sogorb and Vilanova, 2002). Increased resistance to penetration through changes in cuticle and serine endopeptidase gene expression have also been implicated in organophosphate and pyrethroid resistance (David et al, 2014;Lilly et al, 2016;Tandonnet et al, 2020;Zimmer et al, 2017). Environmental heterogeneity and unknown population genetic histories can complicate interpretation of resistance mechanisms in field-collected populations and frustrate accurate estimations of relative fitness or adaptation (Feyereisen et al, 2015;Pélissié et al, 2018).…”