**7. Genomic perspectives for pest control**

**5. Metabolic detoxication of pesticides**

340 Insecticides Resistance

which are currently used as pesticides.

**6. Insensitive target site**

is the target site of pyrethroid pesticides [36, 37].

the para-type sodium channel gene [22].

Plant–insect coevolutionary interactions drive species diversification and the set of genetic traits that allow pest species to survive exposure to a wide variety of secondary metabolites produced by plants. Such genetic traits evolved through evolutionary history, involving several highly specialized multigene families that are responsible for detoxication mechanisms of biotic and xenobiotic compounds. Examples of these multigene families include the glutathione transferases, mixed function oxidases, and carboxilesterases superfamilies [26]. These supergene families are capable of metabolizing a large amount of chemicals, some of

Some mechanisms of resistance have been identified for several important arthropod vectors. Increased esterase activity is a major component of organophosphates resistance in *Culex* mosquitoes [27]. The enhancement of mix function oxidases also plays an important role in OP and pyrethroid resistance mechanisms [28], and the combination of mixed function oxidases and esterases in high concentrations has been detected in permethrin-resistant mosquitoes [29]. Resistance mechanisms in cockroaches include metabolic detoxication and *Kdr*-type resistance. However, detoxication mechanisms mediated by esterases and oxidases

Modifications of target sites as a result of point mutations on gene sequences have been also identified as mechanisms of resistance. Variations on genes encoding GABA receptors [31, 32], acetylcholinesterase [33], some detoxifying esterases [34, 35], and sodium channel gene sequences (22) have been discovered in different arthropods. The latter has been identified as *Kdr*-type resistance; this variation alters the molecular structure of the sodium channel, which

*Kdr*-type resistance was firstly documented in *R*. *microplus* by He et al. [22]. It was shown that there is a variation in the sodium channel gene sequence at position 2134 where the base substitution of thymine by adenine (T2134A) results in an amino acid change from phenyla‐ lanine to isoleucine on the transmembrane segment 6 (S6), which is located on domain III of

Pyrethroid resistance in arthropods has been associated with nonsynonymous mutation on domains I, II, III, and IV of sodium channel genes [38, 39]. As already mentioned, two important variations have been previously identified in *R. microplus* sodium channel gene, a domain II variation (C190A) and the domain III variation (T2134A). The latter only found in ticks from Texas and Mexico [22, 40–42] and the former reported in Australia, Africa, and South America [23, 41, 42]. Although pyrethroid resistance in Mexican cattle tick populations has been mostly attributed to the domain III variation T2134A [22, 36, 39, 43], some authors have suggested that additional resistance mechanisms to the sodium channel variations must be present, since

have been identified as the most frequent mechanisms of resistance [30].

Applying the genomics approach to pesticide research offers the opportunity to advance our knowledge of the mechanisms of resistance and to find sustainable solutions to problems associated with pesticide resistance diagnosis, prediction, and prevention. This will also expand options to improve integrated pest management programs. In the case of livestock, a more rational use of pesticides could be achieved by combining genomics-based knowledge of acaricide resistance with the use of more efficient anti tick vaccines developed through modern technologies [43, 44].

The use of recombinant DNA technologies and the application of bioinformatics to mine genome databases such as GenBank, are powerful foundations to innovate diagnostic tools based on the identification and amplification of single nucleotide polymorphisms (SNPs) associated to target site insensitivity mechanisms [39, 42, 43]. Recent technologies such as polymerase chain reaction (PCR) is a powerful tool used to amplify or detect SNPs that can be employed as biomarkers of pesticide resistance, which provides an alternative to the time consuming bioassays that mitigates the risk of exposure to pesticides by laboratory personnel [21, 35–39, 44].

Genomics approaches are also enabling the design of new target antigens through *in silico* analysis of transcriptomic and genomic data to develop vaccines against ticks [43, 45], mosquitoes, other biting flies, and parasitic worms, as well as markers for pesticide resistance detection [46, 47]. The integration of molecular methods for pesticide resistance detection, prediction, and vaccine development efforts against hematophagous arthropods is an exciting alternative to manage the emergence of pesticide resistance and to improve vector and vectorborne disease control technologies.
