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Simple Summary  The cotton aphid,  Aphis gossypii  Glover, is a notorious pest in cotton and cucurbit fields. The control of  A. gossypii  has typically relied on the application of chemical insecticides. Sulfoxaflor is the first commercially available sulfoximine insecticide, which exhibits great efficacy against sap-feeding insect pests and has been applied as an alternative insecticide for controlling of  A. gossypii  in China. Consequently,  A. gossypii  quickly developed resistance to this insecticide. Hence, in this study, to clarify the potential detoxifying roles of UGTs (one of the phase II detoxification enzymes) in resistance of  A. gossypii  against sulfoxaflor, the synergistic effects of two synergists (sulfinpyrazone and 5-nitrouracil) against sulfoxaflor were investigated using the susceptible and laboratory-established sulfoxaflor resistant strain (SulR), and the expression levels of 15 UGT genes were determined by qRT-PCR. Furthermore, the involvement of highly upregulated UGTs in sulfoxaflor-resistant strain was functionally tested by RNA interference (RNAi). Our results suggest that overexpression of UGTs contributes to sulfoxaflor resistance in  A. gossypii , which should be useful for understanding sulfoxaflor resistance mechanisms.    Abstract  UDP-glycosyltransferases (UGTs) are major phase II detoxification enzymes that catalyze the transfer of glycosyl residues from activated nucleotide sugars to acceptor hydrophobic molecules and play very important roles in the biotransformation of various endogenous and exogenous compounds. Our previous studies demonstrated that UGTs participated in the detoxification of insecticides in  Aphis gossypii . However, the potential roles of UGTs in  A. gossypii  resistance to sulfoxaflor are still unclear. In this study, two inhibitors of UGT enzymes, sulfinpyrazone and 5-nitrouracil, significantly increased the toxicity of sulfoxaflor to a resistant strain of  A. gossypii , whereas there were no synergistic effects in the susceptible strain. Based on the transcriptome sequencing results, the expression levels of 15 UGTs were analyzed by quantitative real-time PCR, and we found that seven UGT genes were highly over-expressed in a sulfoxaflor-resistant strain compared to the susceptible strain, including  UGT344B4 ,  UGT344C5 ,  UGT344A11 ,  UGT344A14 , and  UGT344L2 . Further suppressing the expression of  UGT344B4 ,  UGT344C5 , and  UGT344A11  by RNA interference significantly increased the sensitivity of resistant aphids to sulfoxaflor, indicating that the overexpression of UGT genes is potentially associated with sulfoxaflor resistance. These results could provide valuable information for further understanding the mechanisms of insecticide resistance.

UDP-Glycosyltransferases from the UGT344 Family Are Involved in Sulfoxaflor Resistance in Aphis gossypii Glover