Pest
management is mostly accomplished by the use of insecticides.
However, the overuse of insecticides has led to the development of
resistance. Glutathione S-transferases (GSTs) are
vital detoxification enzymes involved in insecticide resistance in
insects. In this study, we report the involvement of GSTs in insecticide
resistance to lambda-cyhalothrin in Cydia pomonella, a globally quarantined fruit pest.
A total of 25 GST, including 22 cytosolic genes and 3 microsomal genes,
are identified from the genome database of C. pomonella. These cytosolic genes are further classified into six classes,
including four in delta, eight in epsilon, three in omega, three in
sigma, one in theta, and one in zeta class, as well as two unclassified
genes. The real-time quantitative polymerase chain reaction (RT-qPCR)
shows that the majority of these genes are mainly expressed throughout
the larval stage and in the midgut of the fourth-instar larvae. Exposure
to an LD10 dose of lambda-cyhalothrin
resulted in the upregulation of 17 GST genes. Moreover, mRNA levels
of most GST genes, with the exception of CpGSTe6, CpGSTd2, CpGSTd4, and CpGSTz1, are considerably higher in a lambda-cyhalothrin-resistant
population (ZW_R) than those of susceptible strains. Recombinant CpGSTd1,
CpGSTd3, CpGSTe3, and CpGSTs2 can bind and metabolize lambda-cyhalothrin, with the highest metabolic rate observed for CpGSTd3
but no metabolite(s) was detected, supporting the role of GSTs in
sequestration of lambda-cyhalothrin. Molecular dynamics
simulation analysis indicates that key residues of hydrophobic pocket-derived
lipophilic energy S(lipo) interactions with a hydrophobic pharmacophore
of lambda-cyhalothrin are crucial for metabolism
by CpGSTd3 and further lead to resistance. Our study is the first
to experimentally confirm the involvement of GSTs in lambda-cyhalothrin resistance via sequestration and provides new insights
into resistance management in C. pomonella.