Investigating Cell Signalling and Identifying Therapeutic targets in Acanthamoeba spp.

Acanthamoeba is a free-living amoeba that can found in virtually all soil and water habitats throughout the world. Acanthamoeba lives in all of our homes and can be isolated from kitchen/bathroom taps, showerheads, vacuum cleaner dust and garden soil. Acanthamoeba is a dimorphic organism which exists as a feeding and dividing trophozoite which when it encounters unfavourable conditions forms a highly resistant and dormant cyst stage.

The organism usually feeds bacteria but is an opportunistic pathogen of humans causing a fatal encephalitis in immunocompromised patients as well as a blinding infection of the eye called Acanthamoeba keratitis (AK) in previously healthy individuals. What is particularly worrying about this infection is that there is currently no licenced treatment. An unlicensed treatment does exist which includes the swimming pool disinfectant polyhexamethylene biguanide (PHMB).

Therefore there is an urgent need to identify new drug targets for this infection. Recently we have characterised a catecholamine like receptor in Acanthamoeba which appears to be involved in controlling the encystment process. Although the receptor responds to catecholamines no receptor which shares sequence homology with mammalian catecholamine receptors exists. In order to identify the structure of the receptor this proposal will use a pull down assay approach to purify the receptor. The receptor will then be sequenced and investigated further to determine its role in the encystment process and as a potential therapeutic target.