Tick G protein-coupled receptors as targets for development of new acaricides

Authors: Guerrero, Felicito; Dowd, Scot

Submitted to: Veterinary Parasitology
Publication Type: Book / Chapter
Publication Acceptance Date: 12/10/2008
Publication Date: 9/2/2010
Citation: Guerrero, F., Dowd, S.E. 2010. Tick G protein-coupled receptors as targets for development of new acaricides. In: LaMann, G.V. Veterinary Parasitology. New York, NY: Nova Biomedical Press, Inc. p. 241-250.

Interpretive Summary: The family of proteins known as G protein-coupled receptors (GPCR) are a class of receptors which are targets of many drugs in human medicine and are still being pursued in research programs as promising targets for drug development. GPCRs have been identified in arthropods and with the advent of expressed sequence tag (EST) and genome sequencing projects in the ticks Ixodes scapularis, Rhipicephalus (Boophilus) microplus, and Rhipicephalus appendiculatus there is an opportunity for analyzing these sequence databases to identify tick GPCRs. These tick GPCRs can be identified using specialized GPCR-targeted bioinformatic computer software approaches and investigated for their potential in the development of novel tick control chemical technologies. There is precedence for developing acaricides targeting membrane-associated proteins like the GPCR family, as the pyrethroid, formamidine and macrocyclic lactone families of acaricides target membrane-associated proteins. Current acaricides are becoming less effective due to problems with resistance and new classes of acaricides which attack new targets are desperately needed by the cattle industry. We have used bioinformatics approaches to identify and classify putative tick-specific GPCRs in our R. microplus gene index of assembled EST sequences. Several followup approaches are identified and discussed which can facilitate discovery of chemical compounds which inactivate prioritized tick GPCRs and can serve as lead compounds for evaluation as a potential acaricide.

Technical Abstract: The GPCR class of receptors is a source of many pharmacologicals in human medicine and are still being pursued in research programs as promising targets for drug development. GPCRs have been identified in arthropods and with the advent of expressed sequence tag (EST) and genome projects in the ticks Ixodes scapularis, Rhipicephalus (Boophilus) microplus, and Rhipicephalus appendiculatus there is an opportunity for mining these sequence databases to identify tick GPCRs. These tick GPCRs can be identified using GPCR-targeted bioinformatic approaches and investigated for their potential in the development of novel tick control chemical technologies. There is precedence for developing acaricides targeting membrane-associated proteins like the GPCR family, as the pyrethroid, formamidine and macrocyclic lactone families of acaricides target membrane-associated proteins. Current acaricides are becoming less efficacious due to problems with resistance and new chemistries which attack new targets are desperately needed by the cattle industry. We have used bioinformatics approaches to identify and classify putative tick-specific GPCRs in our R. microplus gene index of assembled EST sequences. Opportunities for using high throughput screening approaches are identified and discussed which can facilitate discovery of chemical compounds which inactivate the GPCR and can serve as an acaricide.