Abstract
The opportunistic pathogen, Acanthamoeba castellanii is the causative agent for the sight threatening infection Acanthamoeba keratitis (AK). It is commonly associated with contact lens wearers, and prevalence is increasing at an alarming rate due to an inadequate preventive strategy to protect the lens from this protist. This problem is compounded by the lack of an effective acanthamoebocide, particularly with cysticidal activity in the contact lens solutions. We have used cytotoxicity assays and a variety of biophysical approaches to show that two molecules with tails made of alkyl carbon, alkylphosphocholines (APCs) and quaternary ammonium compounds (QACs) had significant chain-length dependent efficacy against A. castellanii trophozoites, the latter producing death via permeabilization, and DNA complexing. QACs were more effective than APCs and had activity against cysts. Conversely, the QAC with 12 alkyl carbon chain, was non toxic, its presence increased A. castellanii trophozoites biomass and delayed encystation by 96 h. Interestingly, it was unable to induce excystation and increased trophozoite sensitivity to APC16. These results present a mono- and multi-inhibitor management strategy effective against trophozoites and cysts that may be useful for formulating into contact lense cleaning solutions and reducing AK incidence.
Highlights
Acanthamoeba are free-living protists, existing as active trophozoites and non-replicative cysts characterised by double cellulose cell walls[1]
Our results showed that the alkyl carbon chain lengths (14–18 carbons) and overall change of the molecule were the main determinant for their anti-acanthamoebic activity against A. castellanii, producing death by leakage and DNA complexing
Leakage of DNA, proteins and K+ from A. castellanii trophozoites into the external milieu was noted in QAC18-treated cells (37.5 μg/ml) www.nature.com/scientificreports after 24 h
Summary
Acanthamoeba are free-living protists, existing as active trophozoites and non-replicative cysts characterised by double cellulose cell walls[1]. They have opportunistic tendencies and can cause the diseases, Acanthamoeba keratitis (AK), cutaneous acanthamoebiasis (CA) and granulomatous amoebic encephalitis (GAE)[2,3]. Prevent or delay encystation during treatment with encystment inhibitors specific to encystation metabolic pathways e.g. autophagy[18,19], serine and cysteine proteases and cellulose biosynthesis[20,21] This causes Acanthamoeba to persist long enough as the vulnerable trophozoites[22,23] and to allow a second cytotoxic agent to exert its effect[24]. The results present different strategies for an effective preventive treatment strategy for Acanthamoeba
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