Impact of the nicotinic acetylcholine receptor mutation R81T on the response of European Myzus persicae populations to imidacloprid and sulfoxaflor in laboratory and in the field.

Sulfoxaflor (Isoclast™ active) is a sulfoximine insecticide that is active on a broad range of sap-feeding insects, including species that exhibit reduced susceptibility to currently available insecticides. Colonies of Myzus persicae (green peach aphid) were established from aphids collected in the field from peach (Prunus persica) and nectarine (Prunus persica var. nucipersica) orchards in France, Italy and Spain. The presence of the nicotinic acetylcholine receptor (nAChR) point mutation R81T was determined for all the colonies. Eight of the 35 colonies collected were susceptible relative to R81T (i.e., R81T absent), three of the colonies were found to be homozygous for R81T while 24 colonies had R81T present in some proportion (heterozygous). Sulfoxaflor and imidacloprid were tested in the laboratory against these M. persicae field colonies, which exhibited a wide range of susceptibilities (sulfoxaflor RR = 0.6 to 61, imidacloprid RR = 0.7 to 986) (resistance ratios, RR) to both insecticides. Although sulfoxaflor was consistently more active than imidacloprid against these field collected M. persicae, there was a statistically significant correlation across all colonies between the RRs for imidacloprid and sulfoxaflor (Pearson's r = 0.939, p < 0.0001). However, when a larger group of the colonies from Spain possessing R81T were analyzed, there was no correlation observed for the RRs between imidacloprid and sulfoxaflor (r = 0.2901, p = 0.3604). Thus, consistent with prior studies, the presence of R81T by itself is not well correlated with altered susceptibility to sulfoxaflor. In field trials, sulfoxaflor (24 and 36 gai/ha) was highly effective (~avg. 88-96% control) against M. persicae, demonstrating similar levels of efficacy as flonicamid (60-70 gai/ha) and spirotetramat (100-180 gai/ha) at 13-15 days after application, in contrast to imidacloprid (110-190 gai/ha) and acetamiprid (50-75 gai/ha) with lower levels of efficacy (~avg. 62-67% control). Consequently, sulfoxaflor is an effective tool for use in insect pest management programs for M. persicae. However, it is recommended that sulfoxaflor be used in the context of an insecticide resistance management program as advocated by the Insecticide Resistance Action Committee involving rotation with insecticides possessing other modes of action (i.e., avoiding rotation with other Group 4 insecticides) to minimize the chances for resistance development and to extend its future utility.

Sulfoxaflor - A sulfoximine insecticide: Review and analysis of mode of action, resistance and cross-resistance.

The sulfoximines, as exemplified by sulfoxaflor (Isoclast™active), are a relatively new class of nicotinic acetylcholine receptor (nAChR) competitive modulator (Insecticide Resistance Action Committee [IRAC] Group 4C) insecticides that provide control of a wide range of sap-feeding insect pests. The sulfoximine chemistry and sulfoxaflor exhibits distinct interactions with metabolic enzymes and nAChRs compared to other IRAC Group 4 insecticides such as the neonicotinoids (Group 4A). These distinctions translate to notable differences in the frequency and degree of cross-resistance between sulfoxaflor and other insecticides. Most insect strains exhibiting resistance to a variety of insecticides, including neonicotinoids, exhibited little to no cross-resistance to sulfoxaflor. To date, only two laboratory-based studies involving four strains (Koo et al. 2014, Chen et al. 2017) have observed substantial cross-resistance (>100 fold) to sulfoxaflor in neonicotinoid resistant insects. Where higher levels of cross-resistance to sulfoxaflor are observed the magnitude of that resistance is far less than that of the selecting neonicotinoid. Importantly, there is no correlation between presence of resistance to neonicotinoids (i.e., imidacloprid, acetamiprid) and cross-resistance to sulfoxaflor. This phenomenon is consistent with and can be attributed to the unique and differentiated chemical class represented by sulfoxalfor. Recent studies have demonstrated that high levels of resistance (resistance ratio = 124-366) to sulfoxaflor can be selected for in the laboratory which thus far appear to be associated with enhanced metabolism by specific cytochrome P450s, although other resistance mechanisms have not yet been excluded. One hypothesis is that sulfoxaflor selects for and is susceptible to a subset of P450s with different substrate specificity. A range of chemoinformatic, molecular modeling, metabolism and target-site studies have been published. These studies point to distinctions in the chemistry of sulfoxaflor, and its metabolism by enzymes associated with resistance to other insecticides, as well as its interaction with insect nicotinic acetylcholine receptors, further supporting the subgrouping of sulfoxaflor (Group 4C) separate from that of other Group 4 insecticides. Herein is an expansion of an earlier review (Sparks et al. 2013), providing an update that considers prior and current studies focused on the mode of action of sulfoxaflor, along with an analysis of the presently available resistance / cross-resistance studies, and implications and recommendations regarding resistance management.

Sulfoxaflor efficacy in the laboratory against imidacloprid-resistant and susceptible populations of the green peach aphid, Myzus persicae: Impact of the R81T mutation in the nicotinic acetylcholine receptor.

A key to effective insect pest management and insecticide resistance management is to provide growers with a range of new tools as potential alternatives to existing compounds or approaches. Sulfoxaflor (Isoclast™ active) is a new sulfoximine insecticide which is active on a broad range of sap-feeding insects, including species that have reduced susceptibility to currently used insecticides, such as imidacloprid from the neonicotinoid class. Sulfoxaflor (SFX) and imidacloprid (IMI) were tested in laboratory bioassays to compare the susceptibility of field populations of green peach aphid, Myzus persicae (Sulzer), exhibiting varying degrees of resistance involving an alteration (R81T) to the insect nicotinic acetylcholine receptor. The LC50 values for M. persicae exposed to SFX ranged from 0.09 to 1.31 (mg litre-1), whereas when the same populations were exposed to IMI the LC50 values ranged from 0.6 to 76.2 (mg litre-1). M. persicae were significantly more sensitive to SFX as compared to IMI for nine of the 13 populations tested. For M. persicae populations confirmed to be homozygous susceptible (ss) or heterozygous rs) for the R81T point mutation, there was no significant differences in the observed LC50 values for either SFX or IMI relative to the susceptible reference population (15LP1). However, in all M persicae populations that were homozygous (rr) for the R81T point mutation, susceptibility was significantly less to IMI as compared to the reference population with resistance ratios ranging from 22.1 to 63.5-fold. In contrast, only one homozygous resistant population (15MP9) exhibited a statistically significant change in susceptibility (RR = 10-fold) to SFX as compared to the reference population, which was far less than the 56-fold observed for imidacloprid in that same population. Thus, this study indicates there is no specific correlation between the laboratory efficacy of SFX and IMI in field collected populations in Spain displaying varying degrees of resistance to IMI. Furthermore, the presence of target site resistance in M. persicae to IMI, in the form of the R81T mutation, does not a priori translate to a reduction in sensitivity to sulfoxaflor. Consequently, SFX can be an effective tool for use in insect pest management programs for green peach aphid. These data also serve as a baseline reference for green peach aphid sensitivity to SFX prior to commercial uses in Spain.