DIRECTING DIFFERENTIATION IN THEILERIA-ANNULATA - OLD METHODS AND NEWPOSSIBILITIES FOR CONTROL OF APICOMPLEXAN PARASITES

Apicomplexan parasites are major pathogens of humans and domesticated animals. The ability of these organisms to evade the host immune respo nse and the emergence of drug-resistant parasites indicates a need for the identification of novel control strategies. Ideally, selected tar gets should be shared by a range of apicomplexans and fundamental to p arasite biology. One process of apicomplexan biology which may provide this type of target is the molecular regulation of stage differentiat ion. This paper has reviewed studies carried out on differentiation of Theileria annulata and has highlighted general similarities with othe r apicomplexan differentiation steps. Similarities include asynchrony of differentiation, the loss (attenuation) of differentiation potentia l and an association between reduced proliferation and differentiation . In addition, novel data are presented assessing a possible role for a signal transduction mechanism or a direct involvement of classical h eat-shock polypeptides in regulating differentiation of T. annulata in vitro. These studies, and previously published data, have led to the postulation that progression to the next stage of the life-cycle can b e predetermined and involves the attainment of a quantitative threshol d by regulators of gene expression. A modification of this model takes into account that for certain in-vitro systems, or differentiation st eps in vivo, the process has to be initiated by alteration of the extr acellular environment. Work which has shown that the time taken to ach ieve differentiation can be increased or decreased is also outlined. T he ability to change the timing of differentiation suggests that the a ssociated regulatory mechanism could be manipulated directly to signif icantly influence the outcome of an apicomplexan infection. The observ ation that a number of existing drugs and control strategies may exert their protective effect by altering differentiation potential support s this possibility. (C) 1998 Australian Society for Parasitology. Publ ished by Elsevier Science Ltd. All rights reserved.