Molecular biology of tick acetylcholinesterases

Authors: Temeyer, Kevin

Submitted to: Frontiers in Bioscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2017
Publication Date: 1/1/2018
Citation: Temeyer, K.B. 2018. Molecular biology of tick acetylcholinesterases. Frontiers in Bioscience. 23:1320-1337. https://doi.org/10.2741/4646.
DOI: https://doi.org/10.2741/4646

Interpretive Summary: Acetylcholinesterase (AChE) is an enzyme that is critical to function of the central nervous system of animals. It is a target for organophosphate (OP) pesticides used for pest control. Many pests have become resistant to OP pesticides, often by developing mutations that result in production of AChE that is no longer sensitive to inhibition by OP pesticides. Ticks are blood feeding pests that also transmit a wide variety of disease organisms to humans and animals, and have developed resistance to OP pesticides specifically used to kill ticks. Ticks have far greater complexity in their AChEs than most insects and other pests, suggesting that the AChE enzymes in ticks function in ways that have not previously been discovered. Unlike many other blood feeding pests, ticks remain in close contact with their host animals for prolonged periods. A new report summarizes critical information that is known about tick AChEs and introduces additional scientific literature to support a new idea that tick AChE present in tick saliva may function to control host immune reactions to their presence, thereby protecting the tick from host animal defenses. In addition, the existing literature is also consistent with the idea that AChE in tick saliva may also promote the ability of ticks to harbor and transmit disease organisms to their hosts.

Technical Abstract: Ticks are important hematophagous arthropod ectoparasites and like mosquitoes, are vectors for a wide variety of human and animal pathogens. Ticks have significant world-wide health and economic impacts. In the U.S., major impacts include the ability of the blacklegged tick, Ixodes scapularis, to transmit Lyme disease to humans, and thethreat for reinvasion by cattle fever ticks that can transmit bovine babesiosis and anaplasmosis to livestock. Control of ticks and tick-borne disease remains reliant on use of chemical acaricides; however, ticks have developed resistance to nearly all available acaricides and resistance presents a major challenge for effective control. In the U.S., the organophosphate, coumaphos is a key component of the Cattle Fever Tick Eradication Program. Organophosphate (OP) and carbamate acaricides inhibit the activity of acetylcholinesterase (AChE), an enzyme essential to central nervous system function in both vertebrates and invertebrates. Production of AChE that is resistant to OP inhibition is a major mechanism of resistance in insects and in ticks, and specific mutations in insect AChE genes producing an AChE that is insensitive to inhibition have been well characterized. In contrast, the mechanisms producing resistance to OP inhibition in ticks have not yet been fully elucidated, apparently due to the remarkable complexity of the cholinergic system in ticks and possibly other Acari. To date, at least three paralogous AChEs exhibiting significant differences in primary structure and biochemical kinetics have been characterized in ticks, and quantitative PCR and transcriptomic data indicate genomic amplification and developmentally regulated expression of these tick AChEs. Gene silencing studies suggest that they functionally complement one another in vivo. Further, available data from transcriptomic and genomic studies suggest the existence of a number of additional genes encoding AChE in ticks. Acetylcholine is an ancient molecule involved in cholinergic signaling and physiologic control throughout the animal kingdom, and has even been described in plants and some bacteria. In addition to a critical role in neural transmission, cholinergic systems are critical regulators of vertebrate immune function. Ticks and other Acari exhibit prolonged and intimate contact with their hosts, suggesting potential adaptive functions for such unusual complexity in their cholinergic systems. The presence of AChE in tick saliva was recently reported and a potential role in manipulation of the host immune response was hypothesized. The physiological roles and genetic control of the multiple AChEs in ticks remain unclear, but further elucidation of these mechanisms may provide unique opportunities to understand and manipulate cholinergic involvement in multiple biological systems.