Fipronil resistance

One important group of insecticides, the avermectins, works differently by being agonists and not antagonists as the other, acting on the chloride channels. The avermectins are produced by Streptomyces avermitilies. The binding site is different, and cross-resistance to fipronil, the cyclodienes, and lindane does not seem to occur. The toxic symptoms in insects and mammals are different. Mammals poisoned with avermectins exhibit hyperexcitability, incoordination, and tremor followed by ataxia and paralysis. In insects and nematodes, the hyperexcitation phase is absent. Their symptoms are... 

Rdl homomultimers containing the A2 S mutation, when heterologously-expressed in Xenopus oocytes, were highly resistant to dieldrin and picrotoxinin [43]. Gareftil measurement of the effect of fipronil on wild type D. simulans Rdl homomultimers showed the IC50 for block of the peak current decreased from 31 nM after 15 min of incubation to 3.6 nM after 30 min, in fine with the binding data cited above. Because equilibration of fipronil with mutant receptors is almost complete after 15 min, the resistance ratio increased from only 3 at 15 min to 23 at 30 min [44]. Thus, the level of resistance to channel block by fipronil corresponds very well to the levels measured in bioassays, as discussed in the previous paragraph. 

A second mutation in Rdl, T350M, was isolated from a D. melanogaster strain selected in the laboratory for high levels of resistance to fipronil. This mutation made the peak GABA-activated current five-fold resistant to fipronil. The A302S/ T350M double mutant receptor was 50-fold resistant to fipronil. Nevertheless, even both of these mutations together could not account for the 20 000-fold resistance to fipronil in this strain. Other factors, such as metabolism, were not excluded [44]. 

While dieldrin target-site resistance (Section 29.5.2.2) can confer some level of resistance to fipronil, this cross-resistance has not led to failure of fipronil in the field. However, resistance due to other mechanisms was seen in southeast Asia as early as 1996 in diamondback moth Plutella xylostella), within three years of the introduction of the product. The high intrinsic activity of fipronil and lack of alternatives in the mid-1990s led growers in countries such as Thailand to use it up to 40 times per year on cruciferous crops. By early 1997, many populations were resistant and field failures were widespread. At the same time, use of the... 

Antagonism of the GABA Receptor of Dieldrin-Resistant Houseflies by Fipronil and Its Analogues... 

HJEBOB binding to the head membranes of the dieldrin-resistant (OCR) strain of houseflies was investigated. The OCR houseflies had an alanine-to-serine mutation at the 299-position of the RDL subunit. Scatchard analysis showed that EBOB bound to the head membranes of the OCR houseflies with 4-fold lower affinity than to those of the susceptible (WHO/SRS) strain. The membranes of the OCR strain were found to have 45-fold lower affinity for dieldrin than those of the WHO/SRS strain. By contrast, the membranes of the OCR strain showed only 2-fold lower affinity for fipronil than those of the WHO/SRS strain. The alanine-to-serine mutation does not hinder the binding of fipronil to the housefly GABA receptor. 

We first examined the resistance of the OCR strain to three GABA antagonist/insecticides, i.e., dieldrin, fipronil, and EBOB. Figure 1 shows the dose-mortality curves for the insecticidal activity of dieldrin and fipronil determined 24 h after topical application to the OCR and WHO/SRS strains without any synergist treatment. en estimated using the 24-h LDjo values, the OCR strain was found to be 1800-fold more resistant to dieldrin than was the WHO/SRS strain (LDjo° = 19.7 pg/fly LDjo ° = 10.9 ng/fly), whereas the former was 32-fold more resistant to fipronil than the latter (LDso° = 103 ng/fly = 3.26 ng/fly). These values approximate the reported... 

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