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Title: Acetylcholinesterases of Blood-feeding Flies and Ticks

item Temeyer, Kevin
item Tuckow, Alexander
item Brake, Danett
item Li, Andrew
item Perez De Leon, Adalberto - Beto

Submitted to: Chemico Biological Interactions
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2012
Publication Date: 4/1/2013
Citation: Temeyer, K.B., Tuckow, A.P., Brake, D.K., Li, A.Y., Perez De Leon, A.A. 2013. Acetylcholinesterases of blood-feeding flies and ticks. Chemico Biological Interactions. 203:319-322.

Interpretive Summary: Organophosphate pesticides (OPs) largely replaced the use of DDT in the 1960s and remain in widespread use throughout the world. OPs act by inhibition of the enzyme acetylcholinesterase (AChE). This enzyme is essential for nervous system function in pests and other animals. Many pests affecting human and animal health have developed resistance to OPs, which decreases their effectiveness in pest control. The results of our investigations on AChEs of livestock pests presented here describe research on the identification and characterization of genes coding for AChEs in biting flies, sand flies, and cattle ticks. The cloning and production of recombinant enzymes from these economically important pests allowed the identification of mutations involved in OP resistance. This information facilitates the development of rapid molecular tests and provides the basis for guidance in the selection of control strategies that are cost effective. Our work also helped discover new inhibitors of the sand fly and cattle tick AChE. These novel AChE inhibitors were more potent and selective toward the pest AChEs relative to human and animal AChEs. Further research and development on these lead compounds could translate into safer and more effective products targeting pest AChEs. Additionally, tick AChE genes and their products provide a model system for comparative studies to elucidate the biological intricacies of AChEs in other animals and humans. The translation of this research could enable the development of new treatments for serious medical conditions involving AChEs.

Technical Abstract: Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, including biting flies and ticks. However, resistance to OPs in pests affecting animal and human health has compromised control efficacy. OP resistance often results from mutations producing an OP-insensitive AChE. Our studies have demonstrated production of OP-insensitive AChEs in biting flies and ticks. Complementary DNA (cDNA) sequences encoding AChEs were obtained for the horn fly, stable fly, sand fly, and the southern cattle tick. The availability of cDNA sequences enables the identification of mutations, expression and characterization of recombinant proteins, gene silencing for functional studies, as well as in vitro screening of novel inhibitors. The southern cattle tick expresses at least three different genes encoding AChE in their synganglion, i.e. brain. Gene amplification for each of the three known cattle tick AChE genes and expression of multiple alleles for each gene may reduce fitness cost associated with OP-resistance. AChE hydrolyzes the neurotransmitter, acetylcholine, but may have additional roles in physiology and development. The three cattle tick AChEs possess significantly different biochemical properties, and are expressed in neural and non-neural tissues, which suggest separation of structure and function. The remarkable complexity and key role of AChE in neural transmission have presented significant difficulties for vertebrate studies of its non-catalytic functions. Comparative studies between invertebrate and vertebrate AChEs could enhance our understanding of structure-activity relationships. Research with ticks as a model system offers the opportunity to elucidate non-classical functions of AChE that are conserved between vertebrate and invertebrate organisms. The translation of this research could enable the development of new treatments for serious medical conditions involving AChEs.