Acanthamoeba is an opportunistic protozoan widely distributed in the environment, and can cause severe and even life-threatening infections in humans. Acanthamoeba undergoes two stages during the life cycle: the pathogenic trophozoite stage and the infectious cyst stage. Further, there are two stages during encystment, including the early stage involving autolysis and protein degradation and the late stage with cyst-specific gene expression. Cysteine proteases play an important role in the early stage of encystment, which could be inhibited by the cysteine protease inhibitor E64d. Cysteine proteases are cathepsin L-like enzymes with a conserved catalytic site, expressed in trophozoites and cysts continuously, and are localized in lysosomes, exhibiting highest catalytic activities under acidic condition. Unlike serine proteases, cysteine proteases extensively hydrolyze proteins during the encystment process. The cystic-specific cysteine proteases play a key role in encystment of Acanthamoeba through mediating mitochondrial autophagy, this paper reviews the effects of endogenous cysteine protease inhibitors modulating the encystment process.
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