Chloroquine Has a Cytotoxic Effect on Acanthamoeba Encystation through Modulation of Autophagy

Abstract

ABSTRACTEncystation ofAcanthamoeba castellaniiis associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation ofAcanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested inA. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation ofA. castellanii. However,A. castellaniitrophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encystingAcanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoebadrug. Our findings also suggest that targeting autophagy could be a therapeutic strategy againstAcanthamoebainfection.