Insecticide resistance in the tomato pinworm Tuta absoluta: patterns, spread, mechanisms, management and outlook

Abstract

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is an invasive pest difficult to control. Insecticide application is quite common and remains the prevalent control method particularly in open-field cultivation systems. As a result, insecticide resistance to many chemical classes of insecticides has been described both in South America and in Europe. The development of insecticide resistance is relatively fast in this species, and the main mechanisms involved are altered target-site sensitivity and/or enhanced detoxification, depending on the chemical class. However, insecticide resistance mechanisms do not differ between South America and Europe and are mainly due to simple genotype variations leading to high levels of resistance. The presence of resistance alleles at low frequency, especially against newer chemistry, is of major concern, as they tend to spread with the invasions making tomato pinworm particularly difficult to control. The monitoring methods and management programmes developed for the species benefited from the pro-activity of the Insecticide Resistance Action Committee and its country groups, particularly in Brazil and Spain. Bioassay methods were developed, resistance monitoring activities initiated and resistance management guidance was provided. The implementation of integrated control programmes and appropriate resistance management strategies as part of such programs is of utmost importance to keep tomato pinworm infestations under economic damage thresholds, thus guaranteeing sustainable yields.

Full text

Vol.:(0123456789)
1 3
Journal of Pest Science
https://doi.org/10.1007/s10340-019-01086-9
REVIEW
Insecticide resistance inthetomato pinworm Tuta absoluta: patterns,
spread, mechanisms, management andoutlook
R.N.C.Guedes1 · E.Roditakis2 · M.R.Campos3 · K.Haddi1 · P.Bielza4 · H.A.A.Siqueira5 ·
A.Tsagkarakou2 · J.Vontas6,7 · R.Nauen8
Received: 26 October 2018 / Accepted: 24 January 2019
© Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract
The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is an invasive pest difficult to
control. Insecticide application is quite common and remains the prevalent control method particularly in open-field cultiva-
tion systems. As a result, insecticide resistance to many chemical classes of insecticides has been described both in South
America and in Europe. The development of insecticide resistance is relatively fast in this species, and the main mecha-
nisms involved are altered target-site sensitivity and/or enhanced detoxification, depending on the chemical class. However,
insecticide resistance mechanisms do not differ between South America and Europe and are mainly due to simple genotype
variations leading to high levels of resistance. The presence of resistance alleles at low frequency, especially against newer
chemistry, is of major concern, as they tend to spread with the invasions making tomato pinworm particularlydifficult to
control. The monitoring methods and management programmes developed for the species benefited from the pro-activity of
the Insecticide Resistance Action Committee and its country groups, particularly in Brazil and Spain. Bioassay methods were
developed, resistance monitoring activities initiated and resistance management guidance was provided. The implementation
of integrated control programmes and appropriate resistance management strategies as part of such programs is of utmost
importance to keep tomato pinworm infestations under economic damage thresholds, thus guaranteeing sustainable yields.
Keywords Invasive species· Insecticide resistance patterns· Control failure· Resistance management· Target-site
alteration· Insecticide detoxification
Key message
• Insecticide use is the main management tactic employed
against the tomato pinworm;
• Insecticide resistance is common and globally spread,
based on target-site insensitivity and/or enhanced detoxi-
fication;
• Resistance management tactics were developed and are
key for sustainable control, but global spread of resist-
ance genotypes is a concern;
• Risks of insecticide failure and other consequences of
insecticide resistance are further issues of concern.
Communicated by A. Biondi and N. Desneux.
R. N. C. Guedes, E. Roditakis and R. Nauen have contributed
equally on the manuscript.
Special Issue on Advances in the Management of Tuta absoluta
Review article.
* R. N. C. Guedes
guedes@ufv.br
* E. Roditakis
eroditakis@nagref.gr; eroditakis@gmail.com
* R. Nauen
ralf.nauen@bayer.com
Extended author information available on the last page of the article

Journal of Pest Science
1 3
Early spread andcontrol
Spread inSouth America andcontrol constrains
Invasion of pest species is an ongoing and major concern in
an increasingly globalized world where international trade
and travel favour the introduction, establishment and spread
outside their native ranges (Banks etal. 2015). Such inva-
sions can have a strong impact and elicit profound environ-
mental and economic effects in a broad range of ecosystems
(Soliman etal. 2015; Bradshaw etal. 2016; Hill etal. 2016).
While inspection and quarantine measures are the main
practices to minimize the arrival of invasive pest species,
relying on pesticides remains the major practice to control
such pests once established on a broader scale (Lockwood
etal. 2013; Liebhold etal. 2016). However, the presence
of resistance alleles and the lack of effective insecticides
due to missing registrations at the site of introduction could
facilitate the fast spread of invasive pests. The South Ameri-
can tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera:
Gelechiidae), is one of the most recent examples of such an
invasive pest and of major concern among tomato growers
all over the world.
The tomato pinworm, whose initial description dates
back to 1917, apparently has the Peruvian central highlands
in western South America as its native range (Guedes and
Picanço 2012; Biondi et al. 2018). Historically, T. abso-
luta was exclusively reported from South America and
Easter Island (Ripa etal. 1995). A succession of taxonomic
revisions since the mid-1960s until the mid-1990s finally
resulted in its current species name T. absoluta. This period
coincided with the species’ spread through the South Ameri-
can continent reaching Brazil, the main tomato producer in
the region, in the early 1980s (Guedes and Picanço 2012).
Between the 1980s and late 2000s, the pinworm became the
main tomato pest species in the region; a species notoriously
difficult to control (Desneux etal. 2004; Guedes and Picanço
2012; Biondi etal. 2018).
The tomato pinworm infests young plants by larval pen-
etration into the buds of young plant stems, and once foliage
increases, the leaf-mining larvae attack the leaves leading to
loss in photosynthesis capacity (Guedes and Picanço 2012;
Biondi etal. 2018). Larvae are also known to attack the
tomato fruits leading to serious yield losses and compro-
mising crop production (Desneux etal. 2004; Guedes and
Picanço 2012). The larval feeding habits and plant architec-
ture make T. absoluta a difficult target for insecticide sprays
(Guedes and Siqueira 2012; Biondi etal. 2018). Nonethe-
less, insecticide use was the only effective control method to
prevent outbreaks. Thus, heavy reliance on insecticide use
increased selection pressure, affecting the performance of
important chemical classes of insecticides.
Patterns ofinsecticide use
The immediate threat to tomato production in Neotropical
America led to intensive insecticide use against this pest in
the invaded areas. When the species was first introduced
in Brazil, farmers were applying insecticides 10–12 times
per cultivation cycle. After a few years, this was increased
to more than 30 applications per cropping cycle, i.e. 4–6
weekly sprays (Guedes and Siqueira 2012). However, early
colonization of tomato fields, insect attack to multiple plant
parts and protection by the plant canopy cause difficulty to
control this pest species with insecticides. As a consequence,
the level of insecticide efficacy achieved against the tomato
pinworm is often low, what also favours additional spraying
and insecticide overuse (Biondi etal. 2018). Formulation
adjuvants and improved spraying technology do play major
roles mitigating some of these problems, but the lack of con-
trol alternatives particularly for open-field tomatoes retains
the need of multiple applications throughout the cropping
cycle (Guedes and Siqueira 2012; Guedes and Picanço 2012;
Biondi etal. 2018).
The scenario described above led to a dynamic succes-
sion of changes in the compounds used against the tomato
pinworm in South America since the early spread of this
species in the continent. Organophosphates and pyrethroids
were among the few insecticides available for early T. abso-
luta control in tomatoes. These two classes of insecticides
were used against the tomato pinworm starting from the
1960s and 1980s, respectively (Salazar and Araya 1997,
2001; Siqueira etal. 2000a; Lietti etal. 2005). The use of
organophosphates soon declined, and cartap (a nereistoxin
analogue) and abamectin (an avermectin) became available
and were used in combination with pyrethroids (Siqueira
etal. 2000b, 2001; Guedes and Siqueira 2012). By the late
1990s and early 2000s, the oxadiazine indoxacarb and chi-
tin biosynthesis inhibitors (e.g. diflubenzuron, teflubenzuron
and triflumuron) became available, and particularly the lat-
ter group was quite popular (Silva etal. 2011; Guedes and
Picanço 2012).
Other chemical classes introduced for tomato pinworm
control included the pyrroles (e.g. chlorfenapyr), spinosyns
(e.g. spinosad) and the diamides (e.g. chlorantraniliprole and
flubendiamide) (Silva etal. 2011; Gontijo etal. 2013; Silva
etal. 2016a, b). Organic tomato production systems mostly
rely on spinosad, azadirachtin, and Bacillus thuringiensis
toxins (Bt toxins) (Silva etal. 2011; Biondi etal. 2018).
Early monitoring: evolving methods andpatterns
ofresistance
The frequent use of insecticides facilitated resistance devel-
opment in T. absoluta as shown in resistance monitoring

Journal of Pest Science
1 3
campaigns using different types of bioassays. Early studies
used topical application, followed by filter paper impregna-
tion assays with dried insecticide residue (Salazar and Araya
1997; Siqueira etal. 2000a, b, 2001; Guedes and Siqueira
2012). Later, a more applied leaf-dip method suitable for
both fast- and slow-acting insecticides was developed (Gal-
dino etal. 2011; Silva etal. 2011). This method was subse-
quently validated by the Insecticide Resistance Action Com-
mittee (IRAC) as IRAC Method No. 022 (Roditakis etal.
2013a, b) and became a widely accepted reference.
Resistance monitoring in the tomato pinworm revealed
the dynamic nature of resistance in South America, shifting
with the prevailing pattern of insecticide use. The early use
of organophosphate and pyrethroid insecticides led to initial
detection of resistance to these compounds first in Chile,
later in Brazil and Argentina (Salazar and Araya 1997, 2001;
Siqueira etal. 2000a; Lietti etal. 2005). Pyrethroid resist-
ance became widespread and was most likely introduced
into Europe at the onset of the tomato pinworm invasion
from South America (Salazar and Araya 1997; Siqueira etal.
2000a; Silva etal. 2011; Haddi etal. 2012; Silva etal. 2015).
Low-to-moderate levels of abamectin and cartap resistance
were soon reported and increased subsequently (Siqueira
etal. 2000b, 2001; Silva etal. 2016b), while pyrethroid
resistance decreased to levels lower than tenfold (Silva
etal. 2011). Low-to-moderate levels of indoxacarb resist-
ance were later detected (Silva etal. 2011, 2016b), as well as
high resistance ratios to chitin biosynthesis inhibitors result-
ing in field failure at the peak of their use in the mid-2000s
(Silva etal. 2011).
Increased resistance to chitin biosynthesis inhibitors
favoured the use of spinosad and an increase in resistance of
the latter from low to high levels (Reyes etal. 2012; Campos
etal. 2014, 2015). The latest chemical class of insecticides
launched for tomato pinworm control is the diamides (Nauen
2006). However, after a few years of extensive use, resist-
ance to these compounds was detected both in Brazil and in
Europe (Campos etal. 2015; Roditakis etal. 2015,2017b;
Silva etal. 2016a, 2019). Interestingly, resistance to chlor-
fenapyr was detected, but remained at low levels so far, most
likely due to its limited use (Silva etal. 2016b); something
similar is also observed in the case of Bt toxins (Silva etal.
2011).
Associated risk ofcontrol failure
Insecticide resistance detected in laboratory bioassays does
not necessarily result in control failures under applied con-
ditions. Unlike insecticide resistance, the risk or likelihood
of control failure is rarely surveyed since it requires real-
istic exposure scenarios in respective bioassays, in addi-
tion to standard endpoints obtained in insecticide bioassays
designed for this purpose (Guedes 2017). Nonetheless, the
risk of control failure has received an increased attention
and was recently surveyed and preliminarily mapped for
tomato pinworm in Brazil. The findings discussed the effect
of landscape topography on the spread of tomato pinworm
resistance alleles (Silva etal. 2011; Gontijo etal. 2013; Silva
etal. 2015), and it was suggested that the flat landscape of
the Brazilian savannah seems to favour the spread of insec-
ticide resistance. The concern of potential control failures
and resistance spread has also been discussed for European
hotspots for tomato pinworm (Roditakis etal. 2013b).
European invasion, subsequent spread
andcontrol
Invasion andassociated patterns ofinsecticide use
Outside Neotropical America, this pest was first reported
in Spain in late 2006 (Urbaneja etal. 2007) from where
it further spread to coastal European and North African
countries (Desneux etal. 2011; Campos etal. 2017; Biondi
etal. 2018). Mapping of potential source of invasion into
Europe suggested central Chile as the likely origin (Guille-
maud etal. 2015). Subsequently, T. absoluta invaded Middle
East countries and more recently moved southwards reach-
ing several eastern and western sub-Saharan regions, and
subsequently reaching South Africa by 2016 (Pfeiffer etal.
2013; Brévault etal. 2014; Tonnang etal. 2015; Visser etal.
2017; Sylla etal. 2017; Biondi etal. 2018; Mansour etal.
2018; Santana etal. 2019). Eastward, T. absoluta extended
its range of distribution to India and the Himalayan region
by 2017 (Sankarganesh etal. 2017; Sharma and Gavkare
2017; Han etal. 2018, 2019; Santana etal. 2019), and its
presence, although unconfirmed, was reported from Paki-
stan and Tajikistan (Campos etal. 2017). The presence of
T. absoluta was not yet reported from some major tomato-
producing countries, including China, New Zealand, the
USA and Australia (Biondi etal. 2018).
The introduction of T. absoluta into the Mediterranean
region was accompanied by an extensive use of insecticides
to keep it under control (Desneux etal. 2011), resulting in a
significant increase in both average number of applications
and pest control-related costs (Potting etal. 2013). Initially,
and due to the lack of specifically registered compounds
for tomato pinworm control, growers relied on broad-spec-
trum insecticides such as pyrethroids (Balzan and Moonen
2012). However, such a strategy proved ineffective in pro-
viding suitable control levels and highlighted the need of
introducing new chemicals specifically targeting T. absoluta
combined with field monitoring of insecticide susceptibility
(Roditakis etal. 2013a, b). Since 2009, a wave of insecti-
cide registrations for use against T. absoluta allowed a wider
choice of products. Between 2009 and 2011, the number

Journal of Pest Science
1 3
of active insecticide molecules specifically introduced to
target T. absoluta reached 15 and 18 in Spain and Tunisia,
respectively, encompassing some 13 distinct modes of action
(Desneux etal. 2011; Abbes etal. 2012).
Currently, a large number of insecticides representing
several chemical classes are registered and used against T.
absoluta, depending on the country (Table1). These insecti-
cide classes include organophosphates (chlorpyrifos, metha-
midophos), pyrethroids (deltamethrin, lambda-cyhalothrin,
bifenthrin, permethrin), oxadiazines (indoxacarb), spinosyns
(spinosad, spinetoram), avermectins (abamectin, emamectin
benzoate), pyrroles (chlorfenapyr), benzoylureas (difluben-
zuron, lufenuron, novaluron), diamides (chlorantraniliprole,
flubendiamide), diacylhydrazines (chromafenozide, methox-
yfenozide, tebufenozide), semicarbazones (metaflumizone),
tetranortriterpenoids (azadirachtin) and nereistoxin ana-
logues (cartap) (IRAC 2018). Moreover, commercial for-
mulations of some bio-insecticides based on B. thuringien-
sis and Beauveria bassiana have been also widely used on
tomato crops, as they are often more compatible with the
tomato pinworm natural enemies (Biondi etal. 2012, 2013;
Klieber and Reineke 2016). Other bio-insecticides are also
available, like limonene and borax, but exhibiting more lim-
ited use (Soares etal. 2019).
Invasive (resistant) genotypes
From the status of a key tomato pest only in South Ameri-
can countries, T. absoluta largely and rapidly expanded its
geographical distribution during the last 13years. Since
Table 1 Known molecular mechanisms of resistance for chemical classes of insecticides registered for T. absoluta control
a The chemical class is given in case of more than one active ingredient
b M, metabolic; T, target-site mutation; –, unknown
c Functional evidence missing
d Likely to be cross-resistant to indoxacarb in case of target-site mutations
IRAC
MoA
group
Mode of action Chemical classa or com-
pound
Resist-
ance
described
Type of
resistanceb
Major mechanism of
resistance
References
1B Acetylcholinesterase
inhibitor
Organophosphates Yes T A201ScHaddi etal. (2017)
M Esterase activity up Barati etal. (2018)
3A Voltage-gated sodium
channel modulator
Pyrethroids Yes T M918T, T929I, L1014F Haddi etal. (2012)
T, M M918T, T929I, L1014F Silva etal. (2015)
5 Nicotinic acetylcholine
receptor modulator
Spinosyns Yes M Esterase activity up Campos etal. (2015)
T G275E (α6-subunit) Silva etal. (2016a, b, c)
T Exon deletion
(α6-subunit)
Berger etal. (2016a, b)
6Chloride channel activator Avermectins Yes – – Siqueira etal. (2001)
11 Disruption of midgut
membranes
B.t. toxins ? – – –
13 Uncoupler of oxidative
phosphorylation
Chlorfenapyr ? – – –
14 Nicotinic acetylcholine
receptor blocker
Cartap Yes – – Siqueira etal. (2000a, b)
15 Chitin biosynthesis
inhibitor
Benzoylureas Yes – – Silva etal. (2011)
18 Ecdysone receptor agonist Diacylhydrazines ? – – –
22A Voltage-gated sodium
channel blocker
Indoxacarb Yes T F1845Y, V1848I Roditakis etal. (2017a)
22B Voltage-gated sodium
channel blocker
Metaflumizone ?d– – –
28 Ryanodine receptor
modulator
Diamides Yes T I4790M/T, G4946E/V Roditakis etal. (2017b)
T G4946V, I4790M Douris etal. (2017)
UN Unknown mode of action Azadirachtin ? – –

Journal of Pest Science
1 3
resistance to a range of insecticides was earlier reported in
Brazil, Chile and Argentina before the pinworm invasion
into Europe (Souza etal. 1992; Siqueira etal. 2000a, 2001;
Salazar and Araya 2001; Lietti etal. 2005; Guedes and
Siqueira 2012), it is not surprising that resistance alleles
migrated outside the native geographical range of the pest
into Europe.
Guillemaud etal. (2015) showed that the origin of the
invading populations around the Mediterranean was most
likely from Chile. Alleles conferring resistance to insecti-
cides were initially present at low frequency but increased
upon selection with insecticides. Molecular analysis of the
voltage-gated sodium channel—targeted by pyrethroids—
in T. absoluta, revealed three kdr/super-kdr-type mutations
(M918T, T929I and L1014F) present at high frequencies
within different field strains from both South America and
Europe (Haddi etal. 2012). Similarly, Haddi etal. (2017)
also detected at high frequency an A201S mutation linked
with organophosphate resistance at the gene encoding the
organophosphate target site, acetylcholinesterase (AChE),
in different populations of T. absoluta.
Nonetheless, the presence of these mutations in the invad-
ing populations likely contributed to the fitness and spread
of T. absoluta under the intensive and ongoing insecticide
use against this species. Therefore, the development and use
of diagnostic tests to detect the resistant genotypes in the
invading populations are very important to properly design
suitable management tactics as they will allow the selection
and use of insecticides still effective against the prevailing
resistant mechanisms (Guedes and Siqueira 2012; Haddi
etal. 2012).
Method validation, monitoring andpatterns
ofinsecticide resistance
As mentioned above, initial attempts to control the pest
using typical insecticides for lepidopteran pests such as
pyrethroids and OPs resulted in control failures and major
crop losses. A more concerted approach was followed by
three research groups from Greece, Italy and Spain, who
worked with a leaf-dip bioassay to monitor baseline suscep-
tibility against a number of useful insecticides (Roditakis
etal. 2018). Initial baselines were determined on tomato
pinworm populations collected in Greece to key insecticides
of different modes of action (Roditakis etal. 2013b), such
as diamides, spinosad, emamectin benzoate and indoxacarb.
The susceptibility levels of T. absoluta to the tested
insecticides were stable for several years. However, sig-
nificant chlorantraniliprole resistance levels (> 700-fold)
were detected in 2014 in Italian populations. The affected
greenhouses suffered from major tomato crop losses due
to pest control failure (Roditakis etal. 2015). At that time,
low resistance levels to diamides were also reported in
Greece already indicating development of diamide resist-
ance. Despite the proactive instructional actions performed
by many Greek farmers and agronomists, high resistance
levels (resistance ratio (RR) > 600) were detected in Greece
in 2015 (Roditakis etal. 2018) and subsequently in Israel
(2016), UK (2015–2016; C. Bass, personal communication)
and Spain (2018) (Roditakis etal. 2018; Zimmer 2018).
Additional notable cases of insecticide resistance include
indoxacarb (RR up to 91-fold in 2016/Greece), albeit not
widespread and without associated control failure, and spi-
nosad (RR over 480-fold in 2015–2016/UK; C. Bass, per-
sonal communication).
The development of diamide resistance led to an
increased reliance on alternative modes of action for tomato
pinworm management such as indoxacarb and spinosad.
Very recently, an increasing trend in resistance levels to
registered insecticides has been noticed, indicating a shift
towards multiple resistance in field populations of T. abso-
luta (i.e. simultaneous resistance to different insecticides
based on distinct mechanisms) (Roditakis 2018). This trend
reinforces the need for resistance monitoring efforts using
the established leaf-dip method in different countries and
regions (Konuş 2014; Ugurlu Karaağaç 2015; Yalçin etal.
2015; Cherif etal. 2018; Zibaee etal. 2018). Although the
number of populations tested so far and the range of insec-
ticides evaluated is relatively limited—considering the pre-
sent tomato pinworm spread—substantial knowledge on the
insecticide resistance status among populations of T. abso-
luta was gained at a global scale (see below).
Molecular mechanisms ofinsecticide
resistance
Early cases
With the invasion of T. absoluta in Europe, the scientific
community has seen a considerable increase in publications
dealing with insecticide resistance, its mechanisms and man-
agement in this pest species (Fig.1). In general, the most
frequent mechanisms of resistance to insecticides involve:
(a) increased detoxification by metabolic enzymes such as
cytochrome P450s (CYP450), glutathione S-transferases
and esterases; (b) target-site mutations by amino acid sub-
stitutions/deletions resulting in reduced sensitivity; and of
lesser importance (c) altered behavioural responses and (d)
reduced penetration (Li etal. 2007; Feyereisen etal. 2015).
However, enhanced levels of detoxification enzymes and
altered target sites are those mechanisms most commonly
found also in T. absoluta against a range of chemical classes
of insecticides (summarized in Table1).
The first cases of resistance and control failure with
pyrethroids were observed in South America before the

Journal of Pest Science
1 3
species was introduced into Europe (Salazar and Araya
1997; Siqueira etal. 2000b; Lietti etal. 2005; Silva etal.
2011). Meaning many years before Haddi etal. (2012) could
unravel the mechanisms of pyrethroid resistance in this spe-
cies by showing the presence of target-site mutations in the
voltage-gated sodium channel, similarly to those described
in other pest species (Table1; Rinkevich etal. 2013). Clon-
ing of the para-type sodium channel IIS4-IIS6 region from
resistant strains revealed three mutations commonly associ-
ated with resistance to pyrethroids across a range of insect
species (M918T, T929I and L1014). Genotyping of various
populations of T. absoluta from countries in South America
and Europe revealed the presence of a L1014F mutation at
maximum frequency in almost all the populations (Haddi
etal. 2012; Silva etal. 2015), suggesting its fixation in most
of them. Associated with this mutation, two others greatly
enhancing pyrethroid resistance were also present (called
super-kdr), and leading to observed field failures of pyre-
throid applications.
Pyrethroids may also be metabolized by detoxification
enzymes, such as esterases and CYP450s, but such mecha-
nisms appear to be of limited importance in T. absoluta.
However, over-expressed CYP450s in combination with
target-site mutations can have strong implications for pyre-
throid resistance as recently shown in Anopheles gam-
biae (Vontas etal. 2018). Nonetheless, elevated levels of
CYP450s have been suggested to be involved in tomato pin-
worm resistance against cartap, because their suppression
by piperonyl butoxide increased the susceptibility of car-
tap-resistant strains (Siqueira etal. 2000a). In contrast, only
a minor role was suggested for esterases and glutathione
S-transferases. CYP450s potentially mediate the demeth-
ylation and sulfoxidation of cartap as detoxification mecha-
nism rather than its activation (Lee etal. 2004), which may
explain the suppression of cartap resistance by piperonyl
butoxide in T. absoluta. A major involvement of CYP450
in abamectin resistance was also suggested earlier, aided
by enhanced esterase activity (Siqueira etal. 2001). More
recent studies on insecticide resistance in T. absoluta did
not yet result in the identification of individual CYP450s
driving high levels of metabolic resistance to any chemical
class of insecticides.
Organophosphates have been among those insecticides
failing to control T. absoluta in South America many years
ago, but the mechanisms conferring resistance remained elu-
sive until the invasion of this pest into Europe. Two recent
studies on resistance of T. absoluta to organophosphates
showed the presence of the mutation A201S in the acetyl-
cholinesterase (ace1) gene (Haddi etal. 2017; Zibaee etal.
2018). The authors concluded that this mutation was already
present in the invading population(s) of the tomato pinworm,
which is consistent with the organophosphate use and resist-
ance history in South America (Salazar and Araya 1997;
Siqueira etal. 2000a; Lietti etal. 2005).
Recent cases
A number of insecticides recently introduced for Lepidop-
tera control also worked well against leaf-mining species
including T. absoluta. Among them, spinosyns (macrocyclic
lactones) comprise insecticides derived from the soil bac-
terium Saccharopolyspora spinosa, represented by spino-
sad (a natural compound) and the semi-synthetic derivative
spinetoram (Crossthwaite etal. 2017). They act by bind-
ing to an allosteric site at nicotinic acetylcholine receptors
(nAChR), and since the first field-relevant case of spinosad
resistance in the beet armyworm, Spodoptera exigua (Hüb-
ner) (Moulton etal. 2000), various other failures in different
pest species were reported (Sparks etal. 2012).
Resistance to spinosad was first reported in T. abso-
luta populations from Chile with a potential involvement
of CYP450 and esterases as the main mechanisms (Reyes
etal. 2012). Two years later, Campos etal. (2014) reported
autosomal, recessive and monogenic resistance to spino-
sad in a population of T. absoluta from Brazil with high
cross-resistance to spinetoram. This population did not
show resistance to other insecticides tested, and the lack of
elevated detoxification enzyme levels and synergism sug-
gested target-site insensitivity as the potential mechanism
of spinosad resistance. Ultimately, resistance of T. absoluta
to spinosyns was associated with a single mutation G275E
in the α6 subunit of the nAChR (Silva etal. 2016c), as
described earlier in the western flower thrips (Puinean etal.
2013). However, because the frequency of this mutation
in the selected strain was as low as in the parental strain,
Silva etal. (2016c) speculated that other mechanisms may
contribute to the observed resistance level, thus adding
Fig. 1 Cumulative number of publications on insecticide resistance in
Tuta absoluta (survey conducted using SciFinder® linked to Chemical
Abstracts Services (CAS))

Journal of Pest Science
1 3
complexity to the initial scenario of monogenic resistance
(Campos etal. 2014). Indeed, an exon-skipping event that
resulted in the expression of a non-functional α6 subunit of
the nAChR in spinosad-resistant strains was later reported
(Berger etal. 2016a, b). The authors provided functional
electrophysiological evidence that spinosad no longer affects
nAChR receptors devoid of the exon sequence, albeit they
have not provided direct evidence since they expressed a
homo-pentameric nAChR consisting of α7 subunits which
are considered the closest vertebrate homologs of insect α6
subunits. Additional target-site mutations described and
conferring spinosad resistance in other pests include indels,
resulting in premature stop codons leading to loss of func-
tion in truncated α6 subunits (Scott 2008).
Diamides were the latest chemical class of insecticides
launched to the market with initial registrations for the
diamondback moth (Plutella xylostella (L.)) control in the
Philippines and Thailand (Nauen 2006). Diamide insecti-
cides bind to insect ryanodine receptors, which are large
homotetrameric calcium channels mediating upon activa-
tion calcium release from intracellular stores in neuromus-
cular tissue, leading to muscle contraction (Lümmen 2013).
Indeed, the first case of insect resistance to diamide insec-
ticides was reported in P. xylostella from Philippines and
Thailand (Troczka etal. 2012), followed by China (Wang
and Wu 2012) and several other countries, including India,
Japan, Korea, Vietnam and USA (Steinbach etal. 2015).
However, soon after diamondback moth, Roditakis etal.
(2015) and Silva etal. (2016a) reported the first cases of
diamide resistance in greenhouse and field populations of
T. absoluta, respectively, and Silva etal. (2019) confirmed
altered target-site resistance reported earlier by Roditakis
etal. (2017a, b).
Troczka etal. (2012) elucidated the mechanism of resist-
ance to diamides in the diamondback moth and detected a
G4946E mutation in the C-terminal transmembrane domain
of the ryanodine receptor. This mutation was associated with
diamide resistance and evolved independently in Philippine
and Thailand populations of P. xylostella. Later on, Stein-
bach etal. (2015) provided functional evidence by radio-
ligand binding studies that the mutation is indeed confer-
ring resistance to diamides. Other mutations such as an
I4790M described in Chinese strains of diamondback moth
(Guo etal. 2014) were close to G4946E as shown by ryano-
dine receptor homology modelling (Steinbach etal. 2015).
Diamide resistance levels found in European and Brazilian
strains of T. absoluta were as high as those reported for dia-
mondback moth, thus encouraging the investigation of the
possible role of target-site mutations (Table1). Roditakis
etal. (2017b) sequenced respective domains of the ryano-
dine receptor gene of diamide-resistant T. absoluta and
indeed detected two mutations, G4903E and I4746M, corre-
sponding to the positions already described for P. xylostella.
The authors also detected two novel mutations, G4903V
and I4746T, in some of the resistant T. absoluta strains, and
radioligand binding studies with thoracic membrane prepa-
rations provided functional evidence that these mutations
alter the affinity of the Tuta ryanodine receptor to diamides.
Nevertheless, the amino acid substitution G4903E/V is
considered the most important to define the sensitivity of
lepidopteran ryanodine receptors to diamides (Nauen and
Steinbach 2016). This perception is supported by recent cel-
lular studies on functionally expressed ryanodine receptor
constructs carrying the G4946E mutation (Troczka etal.
2015), and by CRISPR/Cas9 genome-edited fruit flies car-
rying the G4903V mutation (Douris etal. 2017).
Indoxacarb and metaflumizone are the major sodium
channel blockers in the market and used against T. absoluta.
No resistance to metaflumizone has been reported up to date
in T. absoluta (Karaagaç 2015; Silva etal. 2016b; Table1).
In contrast, resistance to indoxacarb was reported in T.
absoluta (Silva etal. 2011; Roditakis etal. 2013b). Rodi-
takis etal. (2017a) reported two mutations (F1845Y and
V1848I) in the voltage-gated sodium channel of T. absoluta
associated with resistance to indoxacarb. These mutations
were previously reported in P. xylostella (Wang etal. 2016)
and impaired both indoxacarb and metaflumizone efficacy.
Therefore, these mutations found in T. absoluta may cause
cross-resistance to both sodium channel blockers, what still
needs to be confirmed.
Insecticide resistance management
Basis
The discovery and development of new insecticides these
days are more difficult and costly than ever before. There-
fore, strategies delaying the fast development of resistance
to new and existing insecticides need to be implemented
in all agri- and horticultural settings (Sparks and Nauen
2015). Any insecticide resistance management (IRM) strat-
egy must be proactive, as resistance is likely to develop if no
actions are taken to prevent it. The basis of an IRM strategy
is composed of two components, one more general aimed
to reduce selection pressure, and another one more specifi-
cally aimed at avoiding selection of resistance mechanisms
(Bielza 2008).
Insecticide resistance is selected by the repeated use of
the same compounds of the same modes of action over many
generations. Therefore, the first component of an IRM strat-
egy seeks to lower the selection pressure by reducing pest
populations and optimizing insecticide use (Bielza 2008).
An Integrated Pest Management (IPM) programme calls for
alternative management strategies, including cultural control
(proper watering and fertilization, sanitation, weed removal,

Journal of Pest Science
1 3
crop rotation and anti-insect nets), behaviourally medi-
ated control (use of pheromone or colour traps), biological
control (use of predators, parasitoids and pathogens), and
genetic control (host plant resistance) (Desneux etal. 2004;
Guedes and Picanço 2012; Biondi etal. 2018). The use of
one or more of these alternative strategies may reduce the
need for insecticides, thus decreasing the selection pressure
on pest population. Moreover, the use of alternate biological
control and/or chemical control in different crop periods may
reduce insecticide selection pressure. Nonetheless, despite
these alternative tools, chemical control remains a primary
tool in many situations, and its use must be optimized.
Another more specific component of an IRM strategy
focuses on avoiding selection of resistance mechanisms.
This component is based on the rotation/alternation of
insecticides without cross-resistance. Here, the key is know-
ing which resistance mechanisms prevail in compromising
insecticide efficacy to avoid inadvertent selection for such
particular resistance mechanisms. Functionally, the tactic
involves avoiding the tank mix or the repeated use of the
same insecticide, mode of action or insecticides affected by
the same resistance mechanism (cross-resistance) (Bielza
2008). The rotation scheme must consider the length of a
pest generation, because it is essential to ensure that suc-
cessive generations of the pest are not exposed to the same
insecticide mode of action or insecticides showing cross-
resistance. Within each generation, a repeated application is
acceptable (block application), but never among generations.
If the resistance mechanisms and cross-resistance patterns
are not fully identified, then rotation schemes should use
insecticides with different modes of action (MoA). To this
end, the MoA Classification Scheme developed by IRAC
is a useful tool to select compounds for a rotation scheme
(Sparks and Nauen 2015).
Current eorts
Soon after the tomato pinworm introduction to Spain,
a proactive IRM strategy was adopted. Stakeholders
involved in controlling T. absoluta collaborated with IRAC
Spain to develop an IRM strategy based on both compo-
nents mentioned above: (a) lower selection pressure by
reducing pest population and optimizing insecticide use
and (b) rotation of insecticides without cross-resistance
(IRAC Spain 2009). Firstly, an IPM approach was pro-
moted adopting non-chemical control methods, such as
traps, insect-proof netting and biological control (Bielza
etal. 2016). In addition, the proper use of insecticides was
encouraged (rates, timing, coverage, intervals, thresholds).
Secondly, a MoA rotation scheme was designed in Spain,
using a window of 30days based on the pest’s genera-
tion time to ensure that consecutive generations are not
exposed to the same MoA (Fig.2). Very importantly, this
IRM strategy was disseminated by massive circulation
among growers, technicians, cooperatives, distributers,
officials, industry, etc., similar to outreach activities in
Fig. 2 Insecticide treatment windows established based on the respec-
tive modes of action (MoA) aiming the management of Tuta abso-
luta and using the minimum duration of a single generation (30days).
Each colour represents a different mode of action. Multiple appli-
cations of the same MoA are possible within a treatment window.
When a treatment window is completed, a different MoA should be
selected for use in the next 30days, and if possible, a different MoA
should even be applied in a third MoA treatment window. The exam-
ple shown is based on a suitable situation with four different MoAs
available and working equally good against T. absoluta. (Color figure
online)

Journal of Pest Science
1 3
Brazil and Greece (i.e. https ://goo.gl/3flIu i, https ://goo.gl/
jXqMC s). Summarizing these experiences, IRAC interna-
tional provides effective recommendations for sustainable
and effective resistance management of T. absoluta (IRAC
2014) (Table2).
Beyond pinworm resistance
Insecticide resistance refers to individuals and populations
of a species, but the consequences of this phenomenon go
beyond these hierarchical levels of organization (Guedes
etal. 2016, 2017), a fact frequently neglected. Insecticide
application, although targeting a single (or few) pest spe-
cies or populations, necessarily reaches other non-targeted
populations and species leading to various consequences.
These consequences are discussed below. Another con-
cern is the expression of insecticide-induced hormesis,
and induction/cross-induction of detoxification enzymes
in the tomato pinworm. However, as neither phenomenon
has yet been reported in the tomato pinworm, they will be
just briefly addressed since they may favour inadvertent
selection for insecticide resistance.
Hormesis, induction andinadvertent selection
Hormesis, or more precisely insecticide-induced hormesis,
is a biphasic dose–response phenomenon characterized by a
stimulatory effect associated with the exposure to low (sub-
lethal) doses of compounds that are toxic at higher doses
(Cutler 2013; Guedes and Cutler 2014; Cutler and Guedes
2017). The concern here is that insecticide-resistant popula-
tions also express hormesis, but at higher doses than suscep-
tible populations (Guedes etal. 2010, 2017). Therefore, the
sublethal doses inducing hormesis for a resistant population
might be as high as the field label rates. This is particularly
important when heterozygotes express an almost completely
resistant phenotype as described for diamide insecticides
in T. absoluta populations carrying a ryanodine receptor
target-site mutation (Roditakis etal. 2017b). In such a case,
the field rate used of an insecticide not only leads to control
failure of the targeted pest species, but will actually favour
the population growth of the resistant population.
The (epigenetic) induction and cross-induction of detoxifi-
cation enzymes is another issue relevant within the context of
insecticide resistance. Detoxification enzymes are broadly rec-
ognized as important insecticide resistance mechanisms when
up-regulated (and over-expressed) in resistant populations
Table 2 Recommendations for sustainable and effective resistance management of the tomato pinworm Tuta absoluta, as issued by the Insecti-
cide Resistance Action Committee (IRAC 2014)
Integrated control measure proposed
Prophylactic measures
Allow a minimum of 6weeks from crop destruction to planting the next crop to prevent carry-over of the pest from previous crop
Between planting cycles, cultivate the soil and cover with plastic mulch or perform solarization
Control weeds to prevent multiplication in alternative weed host (especially Solanum, Datura, Nicotiana)
Use pest-free transplants
Seal greenhouse with high-quality nets suitable for T. absoluta
Remove and destroy attacked plant parts
Behaviour-based measures
Prior to transplanting, install sticky traps
Place pheromone-baited traps to monitor all stages of tomato production, i.e. nurseries, farms, packaging, processing and distribution cen-
tres. Start monitoring 2weeks before planting
As soon as more than 3–4 moths per trap are captured each week, start mass trapping of moths
For mass trapping of moths, use sticky traps or water + oil traps (20–40 traps/ha) baited with pheromone
Keep using pheromone traps for at least 3weeks after removing the crop; this catches remaining male moths
Biological measures
Establish populations of effective biological control agents (e.g. Nesidiocoris tenuis, Necremnus, Trichogramma, Macrolophus, Pseudoap-
anteles, Podisus, Nabis/Metarhizium)
Optimizing insecticide use
Inspect the crop to detect the first signs of damage
Use locally established thresholds to trigger insecticide applications
Select insecticides based on known local effectiveness and selectivity
Use only insecticides registered for control of T. absoluta or lepidopteran leaf miners and always follow the directions for use on the label
of each product
Maintain population levels below economic threshold

Journal of Pest Science
1 3
(Sparks and Nauen 2015). However, the fact that these detoxi-
fication enzymes are inducible should not be neglected, nor
the fact that induction may also take place among insecticide-
resistant populations exposed to sublethal concentrations of
insecticides. This exposure may basically prime the insects
against further exposure to the same or other compounds
(Bielza etal. 2007). This phenomenon is sometimes referred
to as hormetic priming or conditioning and has been detected
for esterases and cytochrome P450 monooxygenases (Rix etal.
2004; Cutler and Guedes 2017).
Hormesis and induction of detoxification enzymes may
both contribute to decreased insecticide efficacy and potential
control failure, albeit not yet described in T. absoluta. How-
ever, both phenomena may also contribute to or even shape
inadvertent selection for insecticide resistance in targeted and
non-targeted species, and tomato crops represent a risk in
this respect. A reason for that is the wide coexistence of two
important pest species, the tomato pinworm and whiteflies,
which usually require frequent insecticide applications for their
control. A recent report of whitefly resistance to cartap and
chlorantraniliprole in Neotropical America, two insecticides
used against the tomato pinworm but not against whiteflies,
reinforce this concern (Dângelo etal. 2018). Past use of cartap
and the current frequent use of the diamide chlorantraniliprole
against the pinworm in the region apparently led to the devel-
opment of resistance to these compounds in whiteflies, what
may compromise the future use of related compounds, like
the diamed cyantraniliprole, against the latter (Siqueira etal.
2000a, b; Silva etal. 2016a, b, c; Roditakis etal. 2017b).
Community stress
Insecticide use, and insecticide resistance as one of its main
consequences, is important in shaping community context and
patterns of community structure (Guedes etal. 2016, 2017).
Insect outbreaks, and particularly secondary pest outbreaks,
are one of the potential consequences of community stress
due to insecticide use and resistance. Curiously, the subject
remains largely neglected with focus on natural enemy assem-
blages, when considered, neglecting even their associated host
complex (Martin etal. 2013; Arias-Martín etal. 2016; Guedes
etal. 2017). This is unfortunate, because when tomato and the
tomato pinworm are considered, the interplay between them
and whiteflies, besides the tomato borer Neoleucinodes elegan-
talis (Guenée) and their natural enemies, do offer a complex
scenario whose potential relevance remains unrecognized.
Knowledge gaps andfuture outlook
The research on insecticide resistance in the tomato pin-
worm increased considerably after its invasion in Europe
(Fig.2). This fact provides new insights for the manage-
ment of the species and concerns about the spread of
insecticide-resistant genotypes to other regions (Guedes
and Siqueira 2012; Haddi etal. 2012; Guillemaud etal.
2015; Biondi etal. 2018). Nonetheless, the knowledge
remains patchy and the information available covers a
limited geography considering the ongoing global expan-
sion of this species. Furthermore, the temporal and spatial
scales of development and spread of insecticide resist-
ance in the tomato pinworm are speculative and would
aid in predicting future concerns on newly invaded or
non-invaded areas. Last, prime information obtained in
the species genetics, population structure, and patterns
and mechanisms of insecticide resistance allowed initial
establishment of resistance management programs, which
require regional adaptation by local experts. However, the
consequences of the implementation of such control strate-
gies on other species are largely neglected and remain a
knowledge gap relevant to the tomato cropping system,
which areworth pursuing. There is good reason to appre-
ciate the level of information produced so far regarding
insecticide resistance in the tomato pinworm, but there
is even more reason to focus ahead attempting to address
several of the largely unexplored points discussed in
this review. The tomato pinworm spread and its ongoing
increase in importance reinforce the need to address major
challenges regarding the spread and control of any invasive
pest by a concerted approach among all stakeholders.
Author contributions
All authors participated in the designing and drafting of
the manuscript, each focusing on the respective area(s)
of expertise. The authors are responsible for the content.
Acknowledgements We thank Drs. A. Biondi and N. Desneux for the
invitation to prepare the presentreview and to the several funding agen-
cies that have been providing financial support for the authors’ research
on insecticide resistance in the tomato pinworm.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All applicable international, national and institutional
guidelines for the care and use of animals were considered in the pre-
sent study.

Journal of Pest Science
1 3
Informed consent The authors of this manuscript accept that the paper
is submitted for publication in the Journal of Pest Science, and report
that this paper has not been published or accepted for publication in
another journal, nor is under consideration at another journal.
References
Abbes K, Harbi A, Chermiti B (2012) The tomato leafminer Tuta abso-
luta (Meyrick) in Tunisia: current status and management strate-
gies. EPPO Bull 42:226–233
Arias-Martín M, García M, José M etal (2016) Effects of three-year
cultivation of Cry1Ab-expressing Bt maize on soil microarthro-
pod communities. Agric Ecosyst Environ 220:125–134
Balzan MV, Moonen AC (2012) Management strategies for the control
of Tuta absoluta (Lepidoptera: Gelechiidae) damage in open-field
cultivations of processing tomato in Tuscany (Italy). EPPO Bull
42:217–225
Banks NC, Paini DR, Baylists KL, Hodda M (2015) The role of global
trade and transport network topology in the human-mediated
dispersal of alien species. Ecol Lett 18:188–199. https ://doi.
org/10.1111/ele.12397
Barati R, Hejazi MJ, Mohammadi SA (2018) Insecticide susceptibil-
ity in Tuta absoluta (Lepidoptera: Gelechiidae) and metabolic
characterization of resistance to diazinon. J Econ Entomol
111:1555–1557
Berger M, Piunean AM, Randall E etal (2016a) Insecticide resistance
mediated by an exon skipping event. Mol Ecol 25:5692–5704
Berger M, Puinean AM, Bielza P, Jacobson R, Field LM, Bass C, Wil-
liamson M (2016) Mechanisms of spinosad resistance in Euro-
pean populations of the tomato leafminer. In: XXV International
Congress of Entomology, 25–30 September, Orlando, FL, USA
Bielza P (2008) Insecticide resistance management strategies against
the western flower thrips, Frankliniella occidentalis. Pest Manag
Sci 64:1131–1138
Bielza P, Espinosa PJ, Quinto V, Abellán J, Contreras J (2007) Syn-
ergism studies with binary mixtures of pyrethroid, carbamate
and organophosphate insecticides on Frankliniella occidentalis
(Pergande). Pest Manag Sci 63:84–89
Bielza P, Garcíaa-Vidal L, Martínez-Aguirre MR (2016) Tuta abso-
luta—insecticide resistance management of this invasive species.
In: XXV international congress of entomology, 25–30 Septem-
ber, Orlando, FL, USA
Biondi A, Desneux N, Siscaro G, Zappala L (2012) Using organic cer-
tified rather than synthetic pesticides may not be safer for biologi-
cal control agents: selectivity and side effects of 14 pesticides on
the predator Orius laevigatus. Chemosphere 87:803–812
Biondi A, Zappalà L, Stark JD, Desneux N (2013) Do biopesticides
affect the demographic traits of a parasitoid wasp and its bio-
control services through sublethal effects? PLoS ONE 8:e76548
Biondi A, Guedes RNC, Wan F-H, Desneux N (2018) Ecology, world-
wide spread, and management of the invasive South American
tomato pinworm, Tuta absoluta: past, present, and future. Annu
Rev Entomol 63:239–258
Bradshaw CJA, Leroy B, Bellard C etal (2016) Massive yet grossly
underestimated global costs of invasive insects. Nat Commun
7:12986
Brévault T, Sylla S, Diatte M, Bernadas G, Diarra K (2014) Tuta abso-
luta Meyrick (Lepidoptera: Gelechiidae): a new threat to tomato
production in Sub-Saharan Africa. Afr Entomol 22:441–444
Campos MR, Rodrigues ARS, Silva WM etal (2014) Spinosad and
the tomato borer Tuta absoluta: a bioinsecticide, an invasive pest
threat, and high insecticide resistance. PLoS ONE 9:e103235
Campos MR, Silva TB, Silva WM etal (2015) Susceptibility of Tuta
absoluta (Lepidoptera: Gelechiidae) Brazilian populations to
ryanodine receptor modulators. Pest Manag Sci 71:537–544
Campos MR, Biondi A, Adiga A, Guedes RN, Desneux N (2017) From
the Western Palaearctic region to beyond: Tuta absoluta 10years
after invading Europe. J Pest Sci 90:787–796
Cherif A, Harbaoui K, Zappalà L, Grissa-Lebdi K (2018) Efficacy of
mass trapping and insecticides to control T. absoluta in Tunisia.
J Plant Dis Prot 125:51–61
Crossthwaite AJ, Bigot A, Camblin P, Goodchild J, Lind RJ, Slater R,
Maienfisch P (2017) The invertebrate pharmacology of insec-
ticides acting at nicotinic acetylcholine receptors. J Pestic Sci
42:67–83
Cutler GC (2013) Insects, insecticides and hormesis: evidence and
considerations for study. Dose-Response 11:154–177
Cutler GC, Guedes RNC (2017) Occurrence and significance of
insecticide-induced hormesis in insects. In: Duke SO, Kudsk P,
Solomon K (eds) Pesticide dose: effects on the environment and
target and non-target organisms. American Chemical Society,
Washington, pp 101–119
Dângelo RAC, Campos MR, Silva PS, Guedes RNC (2018) Insec-
ticide resistance and control failure likelihood of the whitefly
Bemisia tabaci (MEAM1; B biotype): a Neotropical. Ann Appl
Biol 172:88–99
Desneux N, Wajnberg E, Wyckhuys KAG etal (2010) Biological inva-
sion of European tomato crops by Tuta absoluta: ecology, geo-
graphic expansion and prospects for biological control. J Pest
Sci 83:197–215
Desneux N, Luna MG, Guillemaud T, Urbaneja A etal (2011) The
invasive South American tomato pinworm, Tuta absoluta, con-
tinues to spread in Afro-Eurasia and beyond: the new threat to
tomato world production. J Pest Sci 84:403–408
Douris V, Papapostolou KM, Ilias A, Roditakis E, Kounadi S, Riga
M, Nauen E, Vontas J (2017) Investigation of the contribution
of RyR target-site mutations in diamide resistance by CRISPR/
Cas9 genome modification in Drosophila. Insect Biochem Mol
Biol 87:127–135
Feyereisen R, Dermauw W, van Leeuwen T (2015) Genotype to phe-
notype, the molecular and physiological dimensions of resistance
in arthropods. Pest Biochem Physiol 121:61–67
Galdino TVS, Picanço MC, de Morais EGF etal (2011) Metodologia
de bioensaio para estudos de toxicidade de formulações com-
erciais de inseticidas a Tuta absoluta (Meyrick, 1917). Cienc
Agrotecnol 35:869–877
Gontijo PC, Picanço MC, Pereira EJG etal (2013) Spatial and tempo-
ral variation in the control failure likelihood of the tomato leaf
miner, Tuta absoluta. Ann Appl Biol 162:50–59
Guedes RNC (2017) Insecticide resistance, control failure likelihood
and the First Law of Geography. Pest Manag Sci 73:479–484
Guedes RNC, Cutler GC (2014) Insecticide-induced hormesis and
arthropod pest management. Pest Manag Sci 70:690–697
Guedes RNC, Picanço MC (2012) The tomato borer Tuta absoluta in
South America: pest status, management and insecticide resist-
ance. EPPO Bull 42:211–216
Guedes RNC, Siqueira HAA (2012) The tomato borer Tuta absoluta:
insecticide resistance and control failure. CAB Rev Perspect
Agric Vet Sci Nutr Nat Resour 7:1–7
Guedes NMP, Tolledo J, Cor rêa AS, Guedes RNC (2010) Insecticide-
induced hormesis in an insecticide-resistant strain of the maize
weevil, Sitophilus zeamais. J Appl Entomol 134:142–148
Guedes RNC, Smagghe G, Stark JD, Desneux N (2016) Pesticide-
induced stress in arthropod pests for optimized integrated pest
management programs. Annu Rev Entomol 61:43–62
Guedes RNC, Walse SS, Throne JE (2017) Sublethal exposure, insec-
ticide resistance, and community stress. Curr Opin Insect Sci
21:47–53

Journal of Pest Science
1 3
Guillemaud T, Blin A, Legoff I etal (2015) The tomato borer, Tuta
absoluta, invading the Mediterranean Basin, originates from a
single introduction from Central Chile. Sci Rep 5:8371
Guo L, Liang P, Zhou X, Gao X (2014) Novel mutations and
mutation combinations of ryanodine receptor in a chlorant-
raniliprole resistant population of Plutella xylostella (L.). Sci
Rep 4:6924
Haddi K, Berger M, Bielza P, Cifuentes D, Field LM, Gorman K,
Rapisarda C, Williamson MS, Bass C (2012) Identification of
mutations associated with pyrethroid resistance in the voltage-
gated sodium channel of the tomato leaf miner (Tuta absoluta).
Insect Biochem Mol Biol 42:506–513
Haddi K, Berger M, Bielza P etal (2017) Mutation in the ace-1 gene
of the tomato leaf miner (Tuta absoluta) associated with organo-
phosphates resistance. J Appl Entomol 141:612–619
Han P, Zhang Y-N, Lu Z-Z, Wang S, Ma D-Y, Biondi A etal (2018)
Are we ready for the invasion of Tuta absoluta? Unanswered key
questions for elaborating an Integrated Pest Management package
in Xinjiang, China. Entomol Gen 38:113–125
Han P, Bayram Y, Shaltiel-Harpaz L, Sohrabi F, Saji A, Esenali UT
etal (2019) Tuta absoluta continues to disperse in Asia: damage,
ongoing management and future challenges. J Pest Sci. https ://
doi.org/10.1007/s1034 0-018-1062
Hill MP, Clusella-trullas S, Terblanche JS, Richardson DM (2016)
Drivers, impacts, mechanisms and adaptation in insect invasions.
Biol Invasions 18:883–891
IRAC (2014) Tuta absoluta—the tomato leafminer or tomato borer.
Recommendations for Sustainable and Effective Resistance
Management. http://www.irac-onlin e.org/pests /tuta-absol uta/
prese ntati ons/. Accessed 23 Oct 2018
IRAC Spain (2009) Prevención de resistencias en Tuta absoluta. http://
www.irac-onlin e.org/count ries/spain /publi catio ns/. Accessed 23
Oct 2018
Karaagaç SU (2015) Enzyme activities and analysis of susceptibility
levels in Turkish Tuta absoluta populations to chlorantraniliprole
and metaflumizone insecticides. Phytoparasitica 43:693–700
Klieber J, Reineke A (2016) The entomopathogen Beauveria bassiana
has epiphytic and endophytic activity against the tomato leaf
miner Tuta absoluta. J Appl Entomol 140:580–589
Konuş M (2014) Analysing resistance of different T. absoluta (Mey-
rick) (Lepidoptera: Gelechiidae) strains to abamectin insecticide.
Turkish J Biochem 39:291–297
Lee S-J, Caboni P, Tomizawa M, Casida JE (2004) Cartap hydrolysis
relative to its action at the insect nicotinic channel. J Agric Food
Chem 52:95–98
Li X, Schuler MA, Berenbaum MR (2007) Molecular mechanisms of
metabolic resistance to synthetic and natural xenobiotics. Ann
Rev Entomol 52:231–253
Liebhold AM, Berec L, Brockerhoff EG etal (2016) Eradication of
invading insect populations: from concepts to applications. Annu
Rev Entomol 61:335–352
Lietti MMM, Botto E, Alzogaray RA (2005) Insecticide resistance in
argentine populations of Tuta absoluta (Meyrick) (Lepidoptera:
Gelechiidae). Neotrop Entomol 34:113–119
Lockwood JL, Hoopes MF, Marchetti MP (2013) Invasion ecology,
2nd edn. Wiley, New York
Lümmen P (2013) Calcium channels as molecular target sites of novel
insecticides. Adv Insect Physiol 44:287–347
Mansour R, Brévault T, Chailleux A etal (2018) Occurrence, biology,
natural enemies and management of Tuta absoluta in Africa.
Entomol Gen 38:83–112
Martin EA, Reineking B, Seo B, Steffan-dewenter I (2013) Natural
enemy interactions constrain pest control in complex agricultural
landscapes. Proc Natl Acad Sci USA 110:5534–5539
Moulton JK, Pepper DA, Dennehy TJ (2000) Beet armyworm (Spodop-
tera exigua) resistance to spinosad. Pest Manag Sci 56:842–848
Nauen R (2006) Insecticide mode of action: return of the ryanodine
receptor. Pest Manag Sci 62:690–692
Nauen R, Steinbach D (2016) Resistance to diamide insecticides in
lepidopteran pests. In: Horowitz AR, Ishaaya I (eds) Advances
in insect control and in resistance management. Springer,
Dordrecht, pp 219–240
Pfeiffer DG, Muniappan R, Sall D etal (2013) First record of Tuta
absoluta (Lepidoptera: Gelechiidae) in Senegal. Fla Entomol
96:661–662
Potting RP, Van Der Gaag DJ, Loomans A etal (2013) Pest risk
analysis—Tuta absoluta, tomato leaf miner moth. Ministry of
Agriculture, Nature and Food Quality. Plant Protection Service
of the Netherlands, Utrecht
Puinean AM, Lansdell SJ, Collins T etal (2013) A nicotinic acetyl-
choline receptor transmembrane point mutation (G275E) asso-
ciated with resistance to spinosad in Frankliniella occidentalis.
J Neurochem 124:590–601
Reyes M, Rocha K, Alarcón L etal (2012) Metabolic mechanisms
involved in the resistance of field populations of Tuta absoluta
(Meyrick) (Lepidoptera: Gelechiidae) to spinosad. Pestic Bio-
chem Physiol 102:45–50
Rinkevich FD, Du Y, Dong K (2013) Diversity and convergence
of sodium channel mutations involved in resistance to pyre-
throids. Pestic Biochem Physiol 106:93–100
Ripa SR, Rojas PS, Velasco G (1995) Releases of biological con-
trol agents of insect pests on Easter Island (Pacific Ocean).
Entomophaga 40:427–440
Rix RR, Ayyanath MM (2004) Cutler GC (2016) Sublethal concen-
trations of imidacloprid increase reproduction, alter expression
of detoxification genes, and prime Myzus persicae for subse-
quent stress. J Pest Sci 89:581–589
Roditakis E (2018) Insecticide mode of action and resistance man-
agement: lessons learned from the case of T. absoluta. In XI
European Congress of Entomology, pp 56–57, Napoli 2–6 July
Roditakis E, Skarmoutsou C, Staurakaki M (2013a) Toxicity of
insecticides to populations of tomato borer Tuta absoluta
(Meyrick) from Greece. Pest Manag Sci 69:834–840
Roditakis E, Skarmoutsou C, Staurakaki M etal (2013b) Determina-
tion of baseline susceptibility of European populations of Tuta
absoluta (Meyrick) to indoxacarb and chlorantraniliprole using
a novel dip bioassay method. Pest Manag Sci 69:217–227
Roditakis E, Vasakis E, Grispou M etal (2015) First report of T.
absoluta resistance to diamide insecticides. J Pest Sci 88:9–16
Roditakis E, Mavridis K, Riga M, Vasakis E, Morou E, Rison JL,
Vontas J (2017a) Identification and detection of indoxacarb
resistance mutations in the para sodium channel of the tomato
leafminer, T. absoluta. Pest Manag Sci 73:1679–1688
Roditakis E, Steinbach D, Moritz G etal (2017b) Ryanodine recep-
tor point mutations confer diamide insecticide resistance in
tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae).
Insect Biochem Mol Biol 80:11–20
Roditakis E, Vasakis E, García-Vidal L, del Rosario Martínez-Agu-
irre M, Rison JL, Haxaire-Lutun MO, Nauen R, Tsagkarakou
A, Bielza P (2018) A four-year survey on insecticide resist-
ance and likelihood of chemical control failure for tomato leaf
miner T. absoluta in the European/Asian region. J Pest Sci
91:421–435
Salazar ER, Araya JE (1997) Deteccin de resistencia a insecticides
en la polilla del tomate. Simiente 67:8–22
Salazar ER, Araya JE (2001) Tomato moth, Tuta absoluta (Meyrick)
response to insecticides in Arica, Chile. Agric Técnica 61:1–7
Sankarganesh E, Firake DM, Sharma B etal (2017) Invasion of the
South American Tomato Pinworm, Tuta absoluta, in northeast-
ern India: a new challenge and biosecurity concerns. Entomol
Gen 1:335–345

Journal of Pest Science
1 3
Santana PA Jr, Kumar L, Da Silva RS, Picanço MC (2019) Global
geographic distribution of Tuta absoluta as affected by climate
change. J Pest Sci. https ://doi.org/10.1007/s1034 0-018-1057-y
Scott JG (2008) Unraveling the mystery of spinosad resistance in
insects. J Pestic Sci 33:221–227
Sharma PL, Gavkare O (2017) New distributional record of invasive
pest Tuta absoluta (Meyrick) in North-Western Himalayan
Region of India. Natl Acad Sci Lett 40:217–220
Silva GA, Picanço MC, Bacci L etal (2011) Control failure likelihood
and spatial dependence of insecticide resistance in the tomato
pinworm, Tuta absoluta. Pest Manag Sci 67:913–920
Silva WM, Berger M, Bass C etal (2015) Status of pyrethroid resist-
ance and mechanisms in Brazilian populations of Tuta absoluta.
Pestic Biochem Physiol 122:8–14
Silva JE, Assis CPO, Ribeiro LMS, Siqueira HAA (2016a) Field-
evolved resistance and cross-resistance of Brazilian Tuta abso-
luta (Lepidoptera: Gelechiidae) populations to diamide insecti-
cides. J Econ Entomol 109:2190–2195
Silva TBM, Silva WM, Campos MR etal (2016b) Susceptibility levels
of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) to minor
classes of insecticides in Brazil. Crop Prot 79:80–86
Silva WM, Berger M, Bass C etal (2016c) Mutation (G275E) of the
nicotinic acetylcholine receptor α6 subunit is associated with
high levels of resistance to spinosyns in Tuta absoluta (Meyrick)
(Lepidoptera: Gelechiidae). Pestic Biochem Physiol 131:1–8
Silva JE, Ribeiro LMS, Vinasco N etal (2019) Field-evolved resist-
ance to chlorantraniliprole in the tomato pinworm Tuta absoluta:
inheritance, cross-resistance profile, and metabolism. J Pest Sci.
https ://doi.org/10.1007/s1034 0-018-1064-z
Siqueira HAA, Guedes RNC, Picanço MC (2000a) Insecticide resist-
ance in populations of Tuta absoluta (Lepidoptera: Gelechiidae).
Agric For Entomol 2:147–153
Siqueira HAA, Guedes RNC, Picanço MC (2000b) Cartap resistance
and synergism in populations of Tuta absoluta (Lep., Gelechii-
dae). J Appl Entomol 124:233–238
Siqueira HAA, Guedes RNC, Fragoso DB, Magalhaes LC (2001)
Abamectin resistance and synergism in Brazilian populations of
Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). Int J Pest
Manag 47:247–251
Soares MA, Campos MR, Passos LC, Carvalho GA (2019) Botani-
cal insecticide and natural enemies: a potential combination for
pest management against Tuta absoluta. J Pest Sci. https ://doi.
org/10.1007/s1034 0-018-01074 -5
Soliman T, Mourits MCM, Lansink AGJMO, Van Der Werf W (2015)
Quantitative economic impact assessment of invasive plant pests:
what does it require and when is it worth the effort? Crop Prot
69:9–17
Sparks TC, Nauen R (2015) IRAC: mode of action classification and
insecticide resistance management. Pestic Biochem Physiol
121:122–128
Sparks TC, Dripps JE, Watson GB, Paroonagian D (2012) Resistance
and cross-resistance to the spinosyns—a review and analysis.
Pestic Biochem Physiol 102:1–10
Steinbach D, Gutbrod O, Lümmen P etal (2015) Geographic spread,
genetics and functional characteristics of ryanodine recep-
tor based target-site resistance to diamide insecticides in
diamondback moth, Plutella xylostella. Insect Biochem Mol
Biol 63:14–22
Sylla S, Brevault T, Bal AB, Chailleux A, Diatte M, Desneux N etal
(2017) Rapid spread of the tomato leafminer, Tuta absoluta (Lep-
idoptera: Gelechiidae), an invasive pest in Sub-Saharan Africa.
Entomol Gen 36:269–283
Tonnang HEZ, Mohamed SF, Khamis F, Ekesi S (2015) Identifica-
tion and risk assessment for worldwide invasion and spread of
Tuta absoluta with a focus on Sub-Saharan Africa: implica-
tions for phytosanitary measures and management. PLoS ONE
10:e0135283
Troczka B, Zimmer CT, Elias J etal (2012) Resistance to diamide
insecticides in diamondback moth, Plutella xylostella (Lepidop-
tera: Plutellidae) is associated with a mutation in the membrane-
spanning domain of the ryanodine receptor. Insect Biochem Mol
Biol 42:873–880
Troczka BJ, Williams AJ, Williamson MS etal (2015) Stable expres-
sion and functional characterisation of the diamondback moth
ryanodine receptor G4946E variant conferring resistance to
diamide insecticides. Sci Rep 5:14680
Ugurlu Karaağaç S (2015) Enzyme activities and analysis of sus-
ceptibility levels in Turkish T. absoluta populations to chlor-
antraniliprole and metaflumizone insecticides. Phytoparasitica
43:693–700
Urbaneja A, Vercher R, Navarro V etal (2007) La polilla del tomate,
Tuta absoluta. Phytoma Espana 194:16–23
Visser D, Uys VM, Nieuwenhuis RJ, Pieterse W (2017) First records of
the tomato leaf miner Tuta absoluta (Meyrick, 1917) (Lepidop-
tera: Gelechiidae) in South Africa. Bio Invasions Rec 6:301–305
Vontas J etal (2018) Rapid selection of a pyrethroid metabolic enzyme
CYP9K1 by operational malaria control activities. Proc Natl
Acad Sci 115:4619–4624
Wang X, Wu Y (2012) High levels of resistance to chlorantraniliprole
evolved in field populations of Plutella xylostella. J Econ Ento-
mol 105:1019–1023
Wang X-L, Su W, Zhang J-H etal (2016) Two novel sodium channel
mutations associated with resistance to indoxacarb and metaf-
lumizone in the diamondback moth, Plutella xylostella. Insect
Sci 23:50–58
Yalçin M, Mermer S, Kozaci LD, Turgut C (2015) Insecticide resist-
ance in two populations of T. absoluta (Meyrick, 1917) (Lepi-
doptera: Gelechiidae) from Turkey. Turkiye Entomoloji Dergisi
39:137–145
Zibaee I, Mahmood K, Esmaeily M etal (2018) Organophosphate and
pyrethroid resistances in the tomato leaf miner T. absoluta (Lepi-
doptera: Gelechiidae) from Iran. J Appl Entomol 142:181–191
Zimmer CT (2018) Characterization and monitoring of target-site
resistance in the Ryanodine Receptor of the tomato leafminer, T.
absoluta. In: XI European Congress of Entomology, pp 54–55,
Napoli 2–6 July
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.

Journal of Pest Science
1 3
Aliations
R.N.C.Guedes1 · E.Roditakis2 · M.R.Campos3 · K.Haddi1 · P.Bielza4 · H.A.A.Siqueira5 ·
A.Tsagkarakou2 · J.Vontas6,7 · R.Nauen8
1 Departamento de Entomologia, Universidade Federal de
Viçosa, Viçosa, MG36570-900, Brazil
2 Hellenic Agricultural Organisation – ‘Demeter’, Institute
ofOlive Tree, Subtropical Plants andViniculture, Heraklion,
Crete, Greece
3 INRA (French National Institute forAgricultural Research),
Université Côte d´Azur, CNRS, UMA 1355–7254, Institut
Sophia Agrobiotech, 06903SophiaAntipolis, France
4 Departamento de Producción Vegetal, Universidad
Politécnica de Cartagena, Cartagena, Spain
5 Departamento de Agronomia – Entomologia, Universidade
Federal Rural de Pernambuco, Recife, PE52171-900, Brazil
6 Institute ofMolecular Biology andBiotechnology,
Foundation forResearch andTechnology-Hellas,
73100Heraklion, Greece
7 Department ofCrop Science, Pesticide Science Lab,
Agricultural University ofAthens, 11855Athens, Greece
8 Bayer AG, Crop Science Division, R&D, Pest Control,
Alfred Nobel Str 50, 40789Monhein, Germany