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  • br Fipronil resistance associated with A S and

    2021-09-26


    Fipronil resistance associated with A2′S and A2′G mutations Fipronil is a second-generation NCA (Fig. 1), and A2′S and A2′G mutations provide a low level of cross-resistance to fipronil (Cole et al., 1995, Gao et al., 2007). As shown in Table 1, the A2′S MK0752 confers high resistance to dieldrin but low resistance to fipronil. In P. xylostella, the A2′S mutation may be related to fipronil resistance based on the high frequency of the A2′S allele for the Rdl gene found in the fipronil-resistant strain, although the involvement of other factors has been suggested (Li et al., 2006). Approximately 2000-fold fipronil-resistant D. simulans was established by laboratory selection, and the selected strain carried two mutations, A301G mutation which is equivalent to A2′G, and T350M mutation (Le Goff et al., 2005). However, other factors might account for the high degree of fipronil resistance, as suggested by Le Goff et al. (2005). In fact, the survival rate of recombinant D. melanogaster that expressed A301G+T350M mutant RDL GABA receptors (Fig. 2) when exposed to fipronil was lower than that of recombinant D. melanogaster expressing A301G mutant RDL GABA receptors, although the A301G mutation provided moderate resistance to fipronil (Remnant et al., 2014). Recently, An. gambiae carrying A296G +T345M mutation (Fig. 2), which corresponds to A301G+T350M mutation in the D. simulans RDL GABA receptor, was identified among dieldrin-resistant mosquitoes (5). A two-electrode voltage clamp assay using Xenopus laevis oocytes that expressed wild-type, A296G mutant, and A296G+T345M mutant An. gambiae RDL GABA receptors showed that the IC50 values for fipronil were 0.31, 4.43, and 2.94μM, respectively, thereby suggesting that the T345M mutation has little or no effect on fipronil resistance (Taylor-Wells et al., 2015). As the A296G mutation decreased the EC50 value for GABA and the T345M mutation increased the EC50 value for GABA, it was speculated that the T345M mutation may offset structural impact of the A296G mutation (Taylor-Wells et al., 2015). A homozygous A2′S mutation in the Rdl gene was found in 60-fold fipronil-resistant O. oryzae (Nakao et al., 2012a). To understand the role of the A2′S mutation in the O. oryzae RDL GABA receptor subunit, Drosophila S2 cells were transfected with the wild-type and A2′S mutant O. oryzae Rdl genes. A membrane potential assay showed that there was no difference in fipronil sensitivity between the wild-type and A2′S mutant receptor homomers when EC80 GABA was applied (Nakao et al., 2012a). However, an approximately 50-fold reduction in the potency of fipronil was observed with the A2′S mutant receptor homomers when EC95 GABA was applied (Nakao et al., 2012a). By contrast, the fipronil sensitivity of the wild-type receptor homomers was not affected by the application of EC95 GABA. Thus, a concentration-dependent effect of GABA on the insensitivity to fipronil in the A2′S mutant O. oryzae RDL GABA receptor was suggested (Nakao et al., 2012a). Similar results were reported for D. melanogaster RDL GABA receptor subunit homomers (Hosie et al., 1995, Wolff and Wingate, 1998). The A2′S mutation did not reduce the fipronil sensitivity in the linear portion of the GABA concentration–response curve, but the A2′S mutation reduced the fipronil sensitivity in the saturated portion of the GABA concentration–response curve. The GABA content may be an important factor for the A2′S mutation in RDL GABA receptors, particularly if the GABA content is elevated in insects. Extensive use of cyclodienes caused a development of cyclodiene resistance. And A2′S and A2′G mutations showed a low level of cross resistance to fipronil. To obtain high degree of fipronil resistance, factors other than A2′S and A2′G mutations have been suggested (Le Goff et al., 2005, Li et al., 2006, Remnant et al., 2014). Le Goff et al. (2005) suggested the involvement of increased detoxification by glutathione S-transferase. Furthermore, other mutation(s) in the Rdl gene or other RDL-like subunit (s) may contribute to high degree of fipronil resistance (Li et al., 2006, Remnant et al., 2014).