br Experimental section br Conflicts of interest br

Experimental section
Conflicts of interest
Acknowledgments This work was partly supported by INSA-Rouen, Rouen University, CNRS, Labex SynOrg (ANR-11-LABX-0029), Région Haute-Normandie.
Introduction A key component of the integrated management of key pests such as codling moth (Cydia pomonella (L.), Lepidotera: Tortricidae) is establishing an insecticide-resistance management (IRM) program. Codling moth is one of the most damaging pests of pome fruit crops worldwide, although in almost all the areas where such crops are cultivated it affects mainly apple production [1]. As a result of long-term pesticide use, the codling moth has developed resistance to different insecticide modes of action and chemistries, such as neurotoxic insecticides and insect growth regulators [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]], and even to C. pomonella granulovirus (CpGV) (family Baculoviridae) [19]. Worldwide, codling moth insecticide resistance is mainly associated with the increased activity of detoxifying nicotinic acid such as non-specific esterases (ESTs), cytochrome polysubstrate P450 monooxygenases (PSMOs), and glutathione S-transferases (GSTs) [3,14,[20], [21], [22]]. In addition, two target-site mutations (structural changes in the insecticide target proteins that render them less sensitive to an insecticide) have been reported: a F290V replacement in acetylcholinesterase in AChE-1 gene, AChE onwards, involved in resistance to organophosphates and carbamates [23], and a L1014F replacement in the voltage-gated sodium channel gene, kdr onwards, involved in resistance to pyrethroids [24]. The AChE mutation confers phenotypic resistance under both homozygote and heterozygote conditions, whereas the kdr mutation confers it only under the recessive homozygote condition. In codling moth Spanish field populations, insecticide resistance has been associated with three detoxification systems, mainly PSMO in adults and larvae [[14], [15],21,[25], [26]], and to a lesser extent GST and EST in larvae [14,15,25]. As for target-site mutations, Reyes et al. [21,27] found the AChE mutation only in a single Spanish field population from a Catalan (NE Spain) apple-growing area, in a study of the variability of resistance mechanisms worldwide that involved a total of 55 populations from Europe (1 from Spain) and 24 from other continents. This Catalan population came from the same area where the Raz population, selected in laboratory with azinphos-methyl by INRA in Avignon, was sampled and in which the AChE mutation was identified by Cassanelli et al. [23]. The kdr mutation was not detected in this Spanish field population [21,27,28]. The existence of multiple resistance mechanisms increases the difficulty of codling moth control and it interferes with the management programs in the orchards. Brent [29] pointed out that the existence of at least 5% of resistant individuals is required in a population to detect a resistance problem, but Denholm et al. [30] and Hoy [31] reported that resistance is very difficult to manage even when only 10% of the individuals carry resistance genes. It is therefore important to establish an IRM program for Spanish codling moth populations to avoid or delay the increase in the frequency of resistant individuals. This requires the early detection of the existing resistance mechanisms in field populations and knowledge of their extent at local scale. Adult moths with PSMO enhanced activity (PSMO-resistant onwards) from Spanish populations did not show a greater attraction to pure kairomone-baited traps in apple orchards [32], as was reported by Sauphanor et al. [33] for French PSMO-resistant populations. However, PSMO detection in codling moth adults caught during the different flights, in orchards under different crop management systems, was found to be a good tool to assess levels of insecticide resistance in field apple crops [32]. Extensive studies of increases in the metabolic capacity of detoxifying enzymes have been carried out in the Ebro Valley pome fruit production area [[14], [15],25], but not on the extension in the occurrence of the target site sensitivity.