Dr Ronnie Mooney

Project Title: Quaternary Ammonium Compounds (QACs) biodegradation pathway in Acanthamoeba castellanii as a model for understanding drug resistance

Acanthamoeba is an opportunistic parasite associated with the sight threatening disease, Acanthamoeba keratitis, predominantly associated with contact lens use. Contact lens sterilants lack anti-amoebic agents, a situation exacerbated by their ability to induce the formation of resistant parasites. The need for sterilants with anti-amoebic activity, even against the resistant parasite is urgent. Previously, we showed that compounds called Quaternary Ammonium Compounds (QACs), had activity against all Acanthamoeba life stages, but the inactive analogues were used for energy production. We noticed that cells treated with inactive QACs contained high levels of ammonium, suggesting that it was being degraded, possibly by enzymes called amine oxidases. The existence of a pathway that can degrade QACs in the parasite is worrying, and we postulate that if the expression of these enzymes are elevated, the parasite can become resistant to the ‘active’ QACs. The project aims to identify amine oxidases in the parasite genome and investigate their role(s) in inducing QAC resistance if increased. We will also create QAC-resistant parasites to elucidate the pathway the parasite uses to develop resistance to QACs. This project will deliver an anti-amoeba supplement for contact lens cleansing and provide mitigating protocols to combat resistance if misuse produces resistant parasites.