Identification of a novel class of insect glutathione S-transferases involved in resistance to DDT in the malaria vector Anopheles gambiae

Abstract

The sequence and cytological location of five Anopheles gambiae glutathione S-transferase (GST) genes are described. Three of these genes, aggst1-8, aggst1-9 and aggst1-10, belong to the insect class I family and are located on chromosome 2R, in close proximity to previously described members of this gene family. The remaining two genes, aggst3-1 and aggst3-2, have a low sequence similarity to either of the two previously recognized classes of insect GSTs and this prompted a re-evaluation of the classification of insect GST enzymes. We provide evidence for seven possible classes of insect protein with GST-like subunits. Four of these contain sequences with significant similarities to mammalian GSTs. The largest novel insect GST class, class III, contains functional GST enzymes including two of the A. gambiae GSTs described in this report and GSTs from Drosophila melanogaster, Musca domestica, Manduca sexta and Plutella xylostella. The genes encoding the class III GST of A. gambiae map to a region of the genome on chromosome 3R that contains a major DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] resistance gene, suggesting that this gene family is involved in GST-based resistance in this important malaria vector. In further support of their role in resistance, we show that the mRNA levels of aggst3-2 are approx. 5-fold higher in a DDT resistant strain than in the susceptible strain and demonstrate that recombinant AgGST3-2 has very high DDT dehydrochlorinase activity.

Molluscicidal and Mosquitocidal Activities of the Essential oils of Thymus capitatus Hoff. et Link. and Marrubium vulgare L.

“…Lymphatic filariasis infects 120 million people in 73 countries worldwide and continues to be a worsening problem, especially in Africa and the Indian subcontinent 28 . Control of such diseases is becoming increasingly difficult because of increasing resistance to synthetic insecticides 29 .…”

Juvenile hormone induction of glutathione S‐transferase activity in the larval fat body of the common cutworm, Spodoptera litura (Lepidoptera: Noctuidae)

“…They are involved in the detoxification of xenobiotics, protection from oxidative damage, isomerization, and intracellular transportation (Hayes and Pulford, 1995;Yu, 1996). In insects, cytosolic GSTs are classified into six classes, i.e., sigma, zeta, theta, delta, epsilon, omega, plus several unclassified genes (Ranson et al, 2001;Ding et al, 2003;Enayati, et al, 2005). Among them, the delta and epsilon classes, which are unique to insects, are involved in the xenobiotic metabolism (Ranson, et al, 2001).…”

“…In insects, cytosolic GSTs are classified into six classes, i.e., sigma, zeta, theta, delta, epsilon, omega, plus several unclassified genes (Ranson et al, 2001;Ding et al, 2003;Enayati, et al, 2005). Among them, the delta and epsilon classes, which are unique to insects, are involved in the xenobiotic metabolism (Ranson, et al, 2001). Most studies related to insect GSTs have emphasized their roles of detoxification and induction by allelochemicals, drugs, insecticides, and other xenobiotics (Yu, 1984;Kao et al, 1989;Fournier et al, 1992;Yu, 1999;Ranson et al, 2001).…”

“…Among them, the delta and epsilon classes, which are unique to insects, are involved in the xenobiotic metabolism (Ranson, et al, 2001). Most studies related to insect GSTs have emphasized their roles of detoxification and induction by allelochemicals, drugs, insecticides, and other xenobiotics (Yu, 1984;Kao et al, 1989;Fournier et al, 1992;Yu, 1999;Ranson et al, 2001). Feng et al (1999) first reported a dramatic increase of GST during diapause in Choristoneura fumiferana; subsequently, they demonstrated a fluctuating pattern of GST expression throughout its development and implicated the involvement of insect…”

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

“…[11][12][13] It has been shown that the GST Epsilon class isoform 2 from A. gambiae (AgGSTE2) is associated to DDT resistance via two mechanisms: elevated gene expression and catalytic activity of the recombinant enzyme. 14 For this reason, AgGSTE2 is overexpressed in resistant strains and the recombinant protein is efficient at metabolizing DDT. 14,15 Furthermore, we have previously sequenced six new GSTE members in three species of Anopheles, and shown that the GSTE2 gene displays the highest level of conservation among all the GSTEs in the four Anopheles species.…”