Differentiation of pathogenic amoebae: encystation and excystation ofAcanthamoeba culbertsoni — A model

Abstract

Differentiation into dormant cysts and vegetative trophozoites is an inherent character intimately associated with the life cycle and infectivity of pathogenic amoebae. In the case of human intestinal amoebiasis encystation and excystation are of immediate relevance to the process of transmission of the disease from healthy carriers to susceptible individuals. Using a pathogenic free living amoebaAcanthamoeba culbertsoni as a model, considerable progress has been achieved in understanding the mechanism and control of the process of differentiation. The turnover of the regulatory molecule cyclic 3: ’5′ adenosine monophosphate is responsible for triggering the process of encystation. Amoebae bind effector molecules such as biogenic amines to a membrane localized receptor which itself resembles the β-adrenergic receptor of mammalian organisms. The activation of adenylate cyclase or inhibition of cyclic AMP phosphodiesterase maintain the dynamic intracellular cyclic AMP. The cytosol fraction of amoebae has a cyclic AMP binding protein. During encystation, enzymes needed for synthesis of cellulose and glycoproteins are induced. Control is exercised at transcriptional level and the process is subject to catabolic repression.

Excystation of mature amoebic cysts is mediated by glutamic acid and certain other amino acids by an as yet unelucidated mechanism. During excystation there is dormancy break, induction of deploymerizing enzymesviz. two proteases, a cellulase and a chitinase. The empty cysts or cyst walls are digested by these enzymes and their break down products are used for cellular growth. By invoking a flip-flop mechanism of repression and derepression some plausible explanation can be offered for the cascade of biochemical events that sets in when amoeba is ‘turned on’ to encystation or excystation.