Multiple-P450 Gene Co-Up-Regulation in the Development of Permethrin Resistance in the House Fly, Musca domestica

Abstract

This paper reports a study conducted at the whole transcriptome level to characterize the P450 genes involved in the development of pyrethroid resistance, utilizing expression profile analyses of 86 cytochrome P450 genes in house fly strains with different levels of resistance to pyrethroids/permethrin. Interactions among the up-regulated P450 genes and possible regulatory factors in different autosomes were examined in house fly lines with different combinations of autosomes from a resistant house fly strain, ALHF. Eleven P450 genes that were significantly up-regulated, with levels > 2-fold those in the resistant ALHF house flies, were in CYP families 4 and 6 and located on autosomes 1, 3 and 5. The expression of these P450 genes was regulated by trans- and/or cis-acting factors, especially on autosomes 1 and 2. An in vivo functional study indicated that the up-regulated P450 genes also conferred permethrin resistance in Drosophila melanogaster transgenic lines. An in vitro functional study confirmed that the up-regulated P450 genes are able to metabolize not only cis- and trans-permethrin, but also two metabolites of permethrin, PBalc and PBald. In silico homology modeling and the molecular docking methodology further support the metabolic capacity of these P450s for permethrin and substrates. Taken together, the findings of this study highlight the important function of multi-up-regulated P450 genes in the development of insecticide resistance in house flies.

Biological Fitness Cost, Demographic Growth Characteristics, and Resistance Mechanism in Alpha-Cypermethrin-Resistant Musca domestica (Diptera: Muscidae)

“…Metabolic detoxification and/or sodium channel-facilitated target site insensitivity have been recognized as major mechanisms underlying the resistance to insecticides in M. domestica [18][19][20][21][22]. Pyrethroid resistance in M. domestica is often linked with mutations (kdr) as well as increased activities of cytochrome P450 monooxygenases, glutathione S-transferases, and/or general esterases [17,[22][23][24][25].…”

The dual resistance mechanism of CYP325G4 and CYP6AA9 inCulex pipiens pallenslegs according to transcriptome and proteome analysis

“…The increased expression of P450s in insect bodies has been related to improved insecticide detoxification levels, evolutionary selection of insecticides, and the ability of insects to adapt to environmental changes [31, 32]. To date, the CYP6 and CYP9 families have been widely reported.…”

The P450-Monooxygenase Activity and CYP6D1 Expression in the Chlorfenapyr-Resistant Strain of Musca domestica L.

“…For the house fly, this has been demonstrated in pyrethroid-, neonicotinoid-, and spinosad-resistant strains [ 59 ], as well as in specimens with multiple resistance (resistance to pyrethroids, dimethoate, propetamphos, methomyl and azamethiphos, cyromazine, and fipronil) [ 58 ]. At the same time, in the multi-resistant ALHF strain of M. domestica , increased expression (more than 2-fold) was typical mainly for the genes of the CYP4 and CYP6 groups [ 60 ]. Only recently has discussion started on the downregulation of P450-monooxygenase genes involved in proinsecticide activation serving as an insecticide resistance mechanism [ 25 , 43 ].…”

“…In the multi-resistant ALHF strain, 11 genes with >2-fold increased expression compared to susceptible aabys and CS strains were identified. The isolated genes were predominantly related to CYP4 and CYP6 (CYP4G13, CYP4G99, CYP4S24, CYP4E10, CYP4E11, CYP6A36, CYP6A40, CYP6A52, CYP6A58, CYP6D3, CYP6D10) [ 60 ].…”