Resistance to Fipronil in the Common Bed Bug (Hemiptera: Cimicidae)

Cimex lectularius L. populations have been documented worldwide to be resistant to pyrethroids and

neonicotinoids, insecticides that have been widely used to control bed bugs. There is an urgent need to

discover new active ingredients with different modes of action to control bed bug populations. Fipronil, a

phenylpyrazole that targets the GABA receptor, has been shown to be highly effective on bed bugs. However,

because fipronil shares the same target site with dieldrin, we investigated the potential of fipronil resistance

in bed bugs. Resistance ratios in eight North American populations and one European population ranged

from 1.4- to >985-fold, with highly resistant populations on both continents. We evaluated metabolic resistance

mechanisms mediated by cytochrome P450s, esterases, carboxylesterases, and glutathione S-transferases

using synergists and a combination of synergists. All four detoxification enzyme classes play significant but

variable roles in bed bug resistance to fipronil. Suppression of P450s and esterases with synergists eliminated

resistance to fipronil in highly resistant bed bugs. Target-site insensitivity was evaluated by sequencing a fragment

of the Rdl gene to detect the A302S mutation, known to confer resistance to dieldrin and fipronil in other

species. All nine populations were homozygous for the wild-type genotype (susceptible phenotype). Highly

resistant populations were also highly resistant to deltamethrin, suggesting that metabolic enzymes that are

responsible for pyrethroid detoxification might also metabolize fipronil. It is imperative to understand the origins

of fipronil resistance in the development or adoption of new active ingredients and implementation of

integrated pest management programs.