Interaction affinity of Delta and Epsilon class glutathione-s-transferases (GSTs) to bind with DDT for detoxification and conferring resistance in Anopheles gambiae, a malaria vector

Abstract

Background & objectives: The enzyme glutathione-s-transferases (GSTs) are associated with detoxification of DDT, as experimentally proved in Anopheles gambiae. Insect GSTs are classified into six classes and among them Delta and Epsilon class GSTs have been implicated in detoxification of organochlorine insecticides. Both Delta and Epsilon GSTs produce, in total, 24 transcripts that result in the production of corresponding enzyme proteins. However, the conventional assay estimates the level of total GSTs and relates to development of resistance to DDT. Hence, it would be more reliable to estimate the level of the specific class GSTs that shows higher affinity with DDT. This would also lead to design a specific molecular tool for resistance diagnosis.

Methods: Of the 24 GSTs, computational models for 23 GSTs, which are available in Swiss-Prot database, were retrieved and for the remaining one, D7-2, for which no model is available in the data bank, a structural model was developed using the sequence of An. dirus B with a PDB ID of 1R5A as the template. All the models were docked with DDT in the presence of reduced glutathione.

Results: The energy output showed that Delta, D6 has the highest interaction affinity with DDT. Hence, this particular GST (D6) is likely to get elevated on exposure of mosquitoes to DDT.

Interpretation & conclusion: It would be, therefore, possible to design a specific molecular assay to determine the expression level of such high affinity transcript(s) and to use for resistance diagnosis reliably in the vector surveillance programme.