Metabolic Resistance in the Fall Armyworm : An Overview

The Fall Armyworm (FAW), Spodoptera frugiperda (Smith, 1797) (Lepidoptera: Noctuidae), is one of the most important pests in the American continent and has recently become an invasive species in Africa. It’s main form of control is through the use of insecticides, however during the last 40 years, due to continuous spraying and high doses used along with FAW’s high adaptative capacity, developed resistance to different classes of chemical insecticides. One of the main mechanisms enabling resistance in the FAW is by detoxification enzymes or so-called metabolic resistance. P450s, Carboxylesterases and Glutathione-S-Transferases are the main families of enzymes believed to mediate the detoxification process. These enzymes in the FAW, although widely studied, have been difficult to generalize into patterns. This happens mainly because FAW populations can have high genetic variability within the species, as they have different biotypes meaning that they can be morphologically identical but physiologically different and consequently, enzymatic responses to toxic compounds can also differ. There are also differences due to the diversity of biomes in which S. frugiperda is found, which due to adaptations to different host plants and other abiotic factors, it’s hard to predict enzymatic responses in insecticide resistance. In this context we aimed to review the literature regarding these three main enzymes families involved in metabolic resistance in S. frugiperda, by cataloguing, analysing and summarizing these studies.


Introduction
The Fall Armyworm (FAW), Spodoptera frugiperda (Smith, 1797) (Lepidoptera: Noctuidae), is one of the most important pests in the American continent and has recently become an invasive species in Africa, reaching out to about 12 countries in a year, 7 of them in two months (Goergen et al., 2016).Its adults, have high dispersal capacity and can fly up to 100Km per night, allowing its dispersion in several plant species in different regions (Fao, 2017).
Despite the preference for plants of the Poacea family (e.g.maize, rice, sorghum), the FAW can feed on more than 80 species and it frequently reaches the economic threshold, achieving the pest status in several crops of economic importance, such as in cotton and soybean crops (Nagoshi & Meagher, 2004).It is estimated that commonly described as resistant.Resistance to synthetic insecticides in the FAW is believed to be mediated mainly by target site insensibility and metabolic detoxification enzymes (metabolic resistance) (Yu et al., 2003).
Metabolic resistance is one of the most common defense mechanisms in herbivorous insects due to the coevolution of insects and plants, the metabolization by enzymes is a defense to xenobiotics present in the environment.Mainly, metabolic resistance relies on enzymatic systems that can detoxify and/or sequester toxic molecules interrupting or decreasing its harmful effect.These enzymes can convert the toxic compound in a non-toxic form and/or convert it to a more easily excretable form in the insect's body (Després et al., 2007).
Understanding the detoxification process in S. frugiperda though, is a tough task, especially if you consider the species' complexities.There is a large genetic variability within FAW populations, as the same species can have different biotypes, which means that they can be morphologically identical but physiologically different and consequently, enzymatic responses to insecticides can also differ (Nagoshi & Meagher, 2004).There are also differences due to the diversity of biomes in which S. frugiperda is found, which due to adaptations to different host plants and other abiotic factors, it's hard to predict enzymatic responses to insecticide exposure.For example, FAW fed with specific plants, can become more tolerant to insecticides and vice versa (Yu & Ing, 1984;Adamczyk et al., 1997;Silva-Brandão et al., 2017).
Hence metabolic resistance in FAW populations is often associated with phenotypic plasticity, since the production of detoxification enzymes can be induced or supressed in the presence of xenobiotics in their diet or/ and be a result of biotypes and/or specific mutations in genes that transcribe these enzymes, increasing their catalytic capacity in relation to the toxic compound (Després et al., 2007;Silva-Brandão et al., 2017).This processes typically involves 3 major families of enzymes: Monooxygenases (P450s), Glutathione-S-Transferases (GSTs) and Carboxylesterases (CarEs) (Kranthi, 2005).Their detoxification roles metabolizing insecticides and/or allelochemicals is widely studied in the FAW (Table 3).It is possible to find a fair amount of isolated studies correlating insecticide metabolization to these enzymes' increased activity in resistant populations.These studies usually confirm the correlation, by restoring insecticide activity through the use of the enzyme's inhibitor.However, they also tend to ignore important biotic and abiotic factors, such as the biotype, host plant adaptation and/or geographic isolation.Therefore, we aimed to review the literature available regarding these enzymes particularities, patterns of induction and supression and other parameters in the FAW that can affect its response to chemical control.Summarizing this information, from an agricultural perspective may serve as a tool to prevent and predict insecticide susceptibility in a regional level and can also serve as an intelligent tactic to FAW's integrated pest management.

Methods
The information used to write this paper was collected from the Web of Science and Scopus database, the search was done by using the terms "fall armyworm", "resistance", "metabolic", "esterases", "GST" and "P450" from 1979 to June 2017.All studies evaluating monooxygenases (P450s), Glutathione-S-Transferases (GSTs) and Carboxylesterases (CarEs) in S. frugiperda were included, those evaluating other enzymes families and/ or different species were excluded.We summarized the literature found in Table 3.

Metabolic Detoxification
Metabolic detoxification can be divided into phases.Phase I, usually consists in hydrolysis or/ and oxidation processes and phase II, conjugates products from phase I with endogenous compounds, until the subsequent excretion of the xenobiotic from the insect's body (Berbaum & Johnson, 2015).For example, in the detoxification of apolar insecticides, their molecules are converted to less lipophilic substances or into polar metabolites by oxidation, reduction and/or hydrolyses processes, typical reactions of phase I.The insertion of hydrophilic functional groups increases water solubility, converting the xenobiotic into a more easily excretable compound, P450s and Carboxylesterases (CarEs) are usually described as Phase I enzymes.Subsequently in Phase II, the resulting metabolites of phase I are conjugated with endogenous intermediates, which is usually carbohydrates, proteins or compounds with a sulphate component to be excreted, this process is usually mediated by Glutathione-S-Transferase (GST) enzymes (Kranthi, 2005).It is important to notice that P450s, CarEs and GSTs represent large super families of enzymes, with different substrate specificities which means that they can catalyse a plurality of different reactions, in this overview we limited them to the most common reactions related to insecticide detoxification.expressed have wider enzyme cavities than others, enabling them to metabolize a higher spectrum of compounds (Rupasinghe et al., 2007).The pattern of induction| supression of each gene was specific for each chemical compound The same is not expected to occur in the metabolization of synthetic insecticides which is believed to induce just a few specific CYPs.The high majority of these, are believed to be expressed in low levels and only when exposed to insecticides, probably because the decoupling of these enzymes produces reactive oxygen in the cell (Giraudo et al., 2015), suggesting that the genes involved in synthetic insecticides metabolization are expressed in different forms, intensity and number, and that some P450s are probably more sensitive to selection pression then CYPs induced by plant allelochemicals (Yu, 1991;Li et al., 2007).For example, P450s expressed in sf9 cell models from tissues involved in the process of detoxification in the FAW, when exposed to insecticides, had just a few genes expressed, most of them from the CYP9 and CYP6 families (Giraudo et al., 2015).
The confirmation that just a few CYP genes are selected in the insecticide resistance is usually demonstrated by comparing susceptible and resistant populations of S. frugiperda.It is believed that resistant FAW populations have biochemical and immunological properties different from susceptible ones.In a study comparing 18.506 transcripts in resistant and susceptible S. frugiperda to benzoylurea, it was found that 840 transcripts were differently expressed.The analyses, showed that the majority of these transcripts (61.3%) were overexpressed and 38.7% were supressed in the resistant population.The high expression levels of some CYP genes, even without insecticide exposure, showed that gene expression can be constitutive (Diez & Omoto, 2001;Nascimento et al., 2015;Silva-Brandão et al., 2017).
The high selection pressure that FAW can be exposed to, the constant use of high insecticidal doses, indiscriminate use of pesticides and deficient chemical group rotation, accelerates the development of resistance to these chemicals, very different to what happens to plant metabolites, in which high exposure to large amounts of toxic metabolites are usually rare and goes through long processes of biotic and abiotic adaptions through evolutionary years (Després et al., 2015).
Though generalizing and specifying the CYPs involved in each case is not ideal, especially because the same P450 involved in plant allelochemical can also be involved in synthetic pesticide metabolization.There are a few studies demonstrating that, for example, in a study evaluating sequences coding for P450s in the FAW exposed to plant allelochemicals, it was found 42 sequences encoding P450s, distributed among the 14 families.In this study, the majority of these were represented by members of the CYP3, CYP9 and CYP4 families (Giraudo et al., 2015).Very similar results were also observed in FAW resistant to Lufenuron (Benzoylurea), in which CYP3 and CYP4 families were also positively expressed, along of with the members of the CYP9 and CYP6 families (Nascimento et al., 2015).

Carboxylesterases
Carboxylesterases (CarEs) form a large group of metabolic enzymes from Phase 1 that belongs to the hydrolases class.CarEs are enzymes that catalyse the hydrolysis of ester bonds on several substrates containing carboxylic esters, in which the target molecule is broken in two or smaller ones by the addition of water and subsequently converting it into its corresponding components of alcohol and acid (Satoh & Hosokawa, 2006).
CarEs are involved in several endogenous and exogenous processes in insects, such as the metabolism of xenobiotics, development regulation, degradation of pheromones and neurogenesis, their function vary according to the species, body region and developmental stage (Biswa et al., 2010;Durand et al., 2010).α-esterases, β-esterases, juvenile hormone esterases, gliotactins, acetylcholinesterases, neurotactins, neuroligins are enzymes responsible for most of the catalytically active reactions of CarEs (Ranson et al., 2002).
In S. frugiperda, they are a known for mediating resistance to pyrethroid insecticides, carbamates and mainly organophosphates (Yu et al., 2003;Li et al., 2007;Carvalho et al., 2013).Basically, because these insecticides have ester, amide and phosphate bonds in their structures.
In S. frugiperda CarEs' mediated resistance may occur through quantitative changes due to the overproduction of esterases by gene amplification and/or positive regulation of one or two CarEs genes (which may result in inhibition or increase of the number of esterases in the FAW) or by qualitative changes resulting from structural mutations of the enzyme.Due to this functional plurality, resistance mediated by CarEs is usually demonstrated as a result of a combination with other resistance mechanisms, and is therefore commonly related to multiple and/or cross resistance (McCord & Yu, 1987;Satoh & Hosokawa, 2006).
In cases of cross-resistance for example, several studies demonstrate the increase in CarEs activity in association with target site insensibility to the insecticide.In S. frugiperda resistant to carbamates and organophosphates for example, CarEs activity is significantly higher in resistant individuals and the enzyme acetylcholinesterase (AChE) in these populations is less sensitive to inhibition (McCord & Yu, 1987;Bullangpoti et al., 2001;Yu et al., 2003).
AchE is by far the most studied CarE, mainly because of its vital importance in the FAW's nervous system and for that it is also one of the main targets of many insecticides.There for, insecticide metabolization in generally correlated to AChE insensitivity.For example, in S. frugiperda resistant to organophosphates, isoforms of AChE are detected conferring resistance to most organophosphates tested.In this same study the EST9555 gene, was also over expressed, and by annotation it was observed that the S. frugiperda's sequence was very similar to the Myzus persicae (Hemiptera: Aphididae) sequence encoding for the carboxylase E4 enzyme (Carvalho et al., 2013).In M. persicae, the CarE E4 is known to confer resistance to many organophosphates and carbamates.It's recombinant form when expressed in Escherichia coli exposed to a carbamate, was responsible to hydrolyse 64% of it in 2.5 hours and an organophosphate in 1.25 hours (Lan et al., 2005).
Even though widely studied there are currently few functional data on purified and/or recombinant CarEs and their specific physiological role in S. frugiperda.Much of the studies in the FAW are demonstrative studies correlating the increase of esterases and esterases activity with the decrease of the insecticidal effect which is generally confirmed by its inhibition using synergists such as S, S, S-tributyl phosphonothioate (DEF) (Usmani & Konwles, 2001).There is also the fact that most current information is inferred from genomes of already sequenced model organisms such as Drosophila melanogaster (Diptera: Drosophilidae) and Bombyx mori (Lepidoptera: Bombycidae), this comparison between different species though, may not be appropriate mainly due to the variation of CarEs expressed in each organism.
Though in recent years, due to technological advances such as interference RNA technology and genome sequencing, it is being possible to investigate FAW's CarEs specificity and functions (Mao et al., 2007;Shi et al., 2016;Gouin et al., 2017).In 2017, when S. frugiperda genome was sequenced, it was possible to demonstrate that, although similar to other species, there are significant differences in the expression of genes related to the metabolism of xenobiotics.It revealed that the S. frugiperda genome have about 24 more genes encoding for esterases than its closest organism B. mori, this is very important mainly because most studies on CarEs in the FAW are deducted from the B. mori genome.
It was also noted that the esterases genes varied according to the FAW's biotype, as some of them are exclusively related to its race.For example, the rice biotype presented 6 more genes expressing CarEs than the maize biotype, their expression and their role in insecticide metabolization though is still uncertain (Gouin et al., 2017).

Glutathione-S-Transferase
Glutathione-S-transferases (GSTs) are a large multifunctional group of enzymes present in mammals, insects, bacteria, protozoa and fungi (Krathi, 2005).They are involved in intracellular transport, biosynthesis of hormones and protection against oxidative stress (Ketterman et al., 2011).Due to a wide range of substrates, they play an important role in the resistance to different classes of insecticides, including organophosphates and pyrethroids.The DDT-dehydrocholinesterase, is the most famous and studied GST, due its direct association to DDT resistance in house flies and mosquitoes (Enayalti et al., 2005).
There are two groups of GSTs, classified according to their location in the cell: the microsomal and the cytosolic.
Although both catalyse similar reactions, microsomal GSTs are not commonly described in the metabolism of insecticides.Cytosolic GSTs form 6 large classes of enzymes identified by Greek letters in the literature, they are the Delta (), Epsilon (), Zeta (), Sigma (), Omega () and Theta () classes (Ranson et al., 2002).
GSTs catalyse the conjugation of a tripeptide, the reduced glutathione (GSH) (Glu-Cys-Gly) to a variety of endogenous and xenobiotic substrates that have electrophilic centres, converting these reactive molecules into less toxic conjugates and/or more hydrophilic compounds (Kirby & Ottea, 1994).They can also metabolize insecticides indirectly by removing free radicals and reactive oxygen produced in the process of degradation of insecticides (Hayes & Pulford, 1995).Although GSTs may be involved in the sequestration of substrates, they are enzymes that generally act after processes of Phase 1 (Krathi, 2005).
The great diversity of GST enzymes in generalist insects such as the FAW reflects the ability of such herbivores to adapt to a wide range of allelochemicals.Like P450s, GSTs are differentially regulated in response to various allelochemical inducers, different stages of development and in specific tissues (Yu & Abo-Elghar, 2000).The complexity of suppression and induction patterns and GST's substrates specificities in S. frugiperda has represented a great difficulty in understanding its functions and roles in insecticide resistance.In the FAW, just like the other enzymes, the exposure to a particular allelochemical in the diet can suppress or stimulate GSTs, how this expression influences the of insecticide metabolization is still a gap to be fulfilled.For example, there are many studies evaluating various plant allelochemical such as phenolic compounds that can inhibit GSTs in the FAW and curiously when facing insecticide exposure, some of these compounds increased insecticides toxicity (Yu & Abo-Elghar, 2000).In contrast, S. frugiperda fed on chickpeas, for example, a potent stimulator of GSTs, were twice as tolerant to organophosphate insecticides as those fed with soybean grains (Yu & Ing, 1984).
A summarized list of GST response to xenobiotic exposure can be found in Table 2.
In most cases individual GST enzymes involved in resistance have not been identified and their action has been implicated by association with other enzymes.In cases where resistance has been studied in more detail, resistance has been attributed to increases in one or more GST enzymes, as a result of gene amplification or more commonly by upregulation, than by qualitative changes in individual enzymes, differently from what happens with the CarEs enzymes for example (Enayalti et al., 2005).
Table 2. Studies evaluating GST response to plant allelochemicals In a study evaluating S. frugiperda gene expression in resistant populations to organophosphate 19 different GST genes were identified, in this population most GST genes were upregulated, depending on its correlation with other detoxification enzymes and interestingly with geographic location.In the same study populations resistant to Bacillus thuringiensis Cry1 toxins (Cry1F and Cry1Ac) and organophosphate from Puerto Rico, had high GTS expression, much more then CarEs and P450s enzymes.This study indicated the potential association of GSTs with multiple resistance/cross-resistance of Bt and organophosphate (Zhu et al., 2015).
In other insects, GTS is commonly described as a phase 2 process in the organophosphate metabolism and it can play a significant role in FAW resistance to these compounds.The conjugation of GSH to organophosphates results in its detoxification in two main pathways: O-dealkylation, where glutathione is conjugated to an alkyl portion of the insecticide and O-alimentation, where the GSH reacts with the group that left.
More recent studies, are also reinforcing GST's involvement in organophosphates metabolization.A study evaluating Expressed Sequence Tags (ESTs) in S. frugiperda resistant to OPs demonstrated that of the 27 ESTs evaluated, 10 were equivalent to GSTs enzymes.Among the significantly overexpressed ESTs, sequences from the epsilon family and from the sigma family were specially overexpressed (Carvalho et al., 2013).The study pointed that these sequences have a 50% similarity to the GST3 encoders of the epsilon family in Plutella xylostella, an insect in which the overexpression of the PXGSTE1 enzyme in resistant strains is able to metabolize organophosphate insecticides (Huang et al., 1998).
The same happen in FAW resistant to pyrethroids, in which all three overexpressed ESTs were GSTs and the sigma family were highly overexpressed (Carvalho et al., 2013).However, even though pyrethroid inducing GSTs is commonly reported in S. frugiperda, GSTs have not yet been detected in its direct metabolism.It is believed that unlike organophosphates, pyrethroids are not metabolized directly by GSTs but they contribute to resistance by protecting the insect from the peroxidation products and the oxidative stress that happens when the FAW is exposed to a xenobiotic (Yu, 2002), it's also believed that GSTs can sequester these molecules until they are metabolized by other detoxification enzymes (Kostaropoulos et al., 2001).
As noted above, GST activity and its involvement in insecticide resistance is still very little understood in detail, even though it's correlation to the process has been demonstrated in several FAW studies (Wheeler et al., 1993;Abo-Elghar & Yu, 2000;Yu, 2002).The recent release of S. frugiperda genome, showed that there is still a lot to look for in the GST superfamily.For example, in the S. frugiperda genome they identified 46 GST genes.When comparing this result to other lepidopterans, they noticed that a recent divergence of the delta and epsilon classes has interestingly expanded in comparison to the other six classes of GST in lepidopterans.They also highlighted differences in the biotypes, in which the rice biotype retained all GST genes from maize, with the exception of GST8 (Gouin et al., 2017).

Final Considerations
Determining the identity of these three large groups of enzymes involved in insecticide metabolism has been difficult due to the lack of knowledge of the complexity of these families in the FAW and the difficulties of identifying truly orthologous genes among different model organisms (Ranson et al., 2002).
Much of what is known today is inferred from other species and more recent studies have shown considerable differences in these enzymes expression, for example there are 15 members of the CYP9 family in S. frugiperda versus 4 members in B. mori and none in P. xylostella, these insects are the closest lepidoptera members used for annotation in most FAW studies, and relevant differences are also reported to happen to GSTs and CarEs families (Giraudo et al., 2015;Gouin et al., 2017).Although these results can be disheartening and generate uncertainties about what we believed to happen in the FAW so far, there is an optimistic perspective about what these news in enzyme detoxification can bring, and a more detailed comprehension of this complexities, can help elucidate their function in the FAW and other insects of economic importance and perhaps this knowledge can also be explored as new targets in the insecticide industry.
What we noticed so far, is that there is a big amount of isolated studies on the FAW's physiology and genomics, and difficulties of finding specificities in S. frugiperda is mainly because its enzyme expression and its related processes are dependent on several other factors, such as environment, host plants interaction and the selection pressure in which S. frugiperda is submitted.There is still a lot to learn about these patterns of repression and induction, as much as these enzyme particularities in highly polyphagous pests such as the FAW.
The importance of this information extrapolates the academic level as it can be a tool to optimize integrated pest management tactics.As noticed in this overview the host plant interaction with tolerance and/or resistance to insecticides should be taken in consideration when planning crops rotation and/or picking a proper insecticide in the market.Rationally choosing a host plant that disfavours the FAW establishment in the field and/or survivorship to spraying can help reduce the costs of control, especially for smallholders in which access to cut edge technology is not always available and the optimization of control measures can bring significant differences in the final production costs.
Since selecting a control method nowadays, commonly ignores the fact that there are differences in S. frugiperda susceptibility to insecticides when fed on different host plants, cultivars and even the same species collected in different continents (Yu, 1982;Hull-Sanders et al., 2007) we strongly propose a regional level analyses as a tool for organizations to guide an intelligent FAW management.Starting by a proper identification of FAW biotypes as well as flora of the region, since changes in enzymatic activity in response to external factors may affect resistance and tolerance to adverse conditions.Unfavourable conditions to the FAW should be explored regionally, especially due to the diversity of biomes in which FAW is present.These factors can also be taken in account, in future investigations, even though restrictions in enzymes studies and the technology available is still very limiting making it almost impossible to consider different variables at the same time.
In this overview we constantly commented on the endogenous roles these enzymes have in the FAW besides xenobiotic metabolization, but a more detailed analyses is needed to find a correlation between these processes.Studies of how and if metabolic enzymes affect other metabolic pathways is also an interesting area to explore.We know that resistance is a complete biological phenomenon that enables the insect to maintain its vital processes and survive in adverse environmental conditions.As so, the metabolic pathways adjacent to the classical detoxification route, may be closely related to a fitness cost and may represent an additional mechanism contributing to resistance.For example, in one of the studies, it was reported that in S. frugiperda resistant to benzoylurea, the transcripts for ubiquinol-cytokine and the reductase complex were also overexpressed.This is particularly interesting because the cytochrome c ubiquinol is not directly linked to insecticide resistance, since its main function is associated with electrons transport in the cellular respiration process (Carvalho et al., 2013).
Besides the almost impossible task to address detoxification enzymes as a unique biological complex in the FAW, we do expect a change in subsequent studies regarding these enzymes as system, especially because of the molecular and genomic advances seen in recent years.Interference RNA, microarrays, free access to SPODOBASE (an EST database from all organs of S. frugiperda) are good examples of technologies that are now becoming more accessible for scientist all over the globe (Nègre et al., 2006;Nascimento et al., 2015).Advances such as the full S. frugiperda genome released in 2017 is now available for more detailed investigations, but for that, the demonstrative and basic studies we have until now need to be properly comprehended, we believe that these studies will guide scientists and technicians along new challenges (Gouin et al., 2017).Therefore, we hope that overviews such as this one, contribute in some way to future studies in search of more sustainable options regarding insecticide use and for a more detailed comprehension of this insect's biology, physiology and behaviour.
and cytosolic) Both GSTs had an antioxidant nature; Cytosolic GSTs showed a broader substrate specificity and was less sensitive to inhibition.Microsomal GST was not induced by xanthotoxin and indole 3-acetonitrile.Inhibitors: Flavonoids, Phenols, a,b-Unsaturated carbonyl, Organotin and Halogenated compound Wheeler et al. (1993) Fall armyworm sensitivity to flavone: limited role of constitutive and induced detoxifying enzyme activity USAKirby and Ottea (1994)   Multiple mechanisms for enhancement of Glutathione S-Transferase activities in Spodoptera frugiperda (Lepidoptera: Noctuidae) USA Adamczyk et al. (1997) Susceptibility of Fall Armyworm Collected from Different Plant Hosts to Selected Insecticides and Transgenic Bt Cotton USA Yu and Abo-Elghar (2000) Allelochemicals as inhibitors of Glutathione S-Transferases in the Fall Armyworm USA Bullangpoti et al. (2001) Antifeedant activity of Jatropha gossypifolia and Melia azedarach senescent leaf extracts on Spodoptera frugiperda (Lepidoptera: Noctuidae) and their potential use as synergist THA Yu (2002) Biochemical characteristics of Microsomal and Cytosolic Glutathione S-Transferases in larvae of the Fall Armyworm, Spodoptera frugiperda (J.E. Smith) USA Yu et al. (2003) Biochemical characteristics of insecticide resistance in the Fall armyworm, Spodoptera frugiperda (J.E.Smith) USA Nègre et al. (2006) SPODOBASE: an EST database for the lepidopteran crop pest Spodoptera frugiperda FR Carvalho et al. (2013) Investigating the Molecular Mechanisms of Organophosphate and Pyrethroid Resistance in the Fall Armyworm Spodoptera frugiperda UK Nascimento et al. (2015) Comparative transcriptome analysis of lufenuron-resistant and susceptible strains of Spodoptera frugiperda (Lepidoptera: Noctuidae) BR Giraudo et al. (2015) Cytochrome P450s from the Fall armyworm (Spodoptera frugiperda): responses to plant allelochemicals and pesticides FR Fazolin et al. (2015) Sinérgico alternativo para o manejo da resistência da lagarta-do-cartucho do milho a piretróides BR Zhu et al. (2015) Evidence of multiple/cross resistance to Bt and organophosphate insecticides in Puerto Rico population of the Fall armyworm, Spodoptera frugiperda EUA Silva-Brandão et al. (2017) Transcript expression plasticity as a response to alternative larval host plants in the speciation process of corn and rice strains of Spodoptera frugiperda BR Flagel et al. (2017) Mutational disruption of the ABCC2 gene in fall armyworm, Spodoptera frugiperda, confers resistance to the Cry1Fa and Cry1A.105insecticidal proteins EUA Gouin et al. (2017) Two genomes of highly polyphagous lepidopteran pests (Spodoptera frugiperda, Noctuidae) with different host-plant ranges FR

Table 3 .
List of metabolic resistance studies in S. frugiperda used as source of information for this overview, organized by chronological order, subject and country of research Reference Country Young and McMillian (1979) Differential Feeding by Two Strains of Fall Armyworm Larvae on Carbaryl Treated Surfaces USA Wood et al. (1981) Influence of Host Plant on the Susceptibility of the Fall Armyworm to Insecticides USA Yu (1982) Induction of Microsomal Oxidases by Host Plants in the Fall Armyworm, Spodoptera frugiperda (J.E. Smith) USA Yu and Ing (1984) Microsomal biphenyl hydroxylase of Fall armyworm larvae and its induction by allelochemicals and host plants.USA McCord and Yu (1987) The Mechanisms of Carbaryl Resistance in the Fall Armyworm Spodoptera frugiperda (J.E. Smith) USA Yu (1991) Insecticide Resistance in the Fall Armyworm, Spodoptera frugiperda (J.E. Smith) USA