Biochemical aspects of egg hatch in endo- and ectoparasites: potential for rational drug design

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Abstract

Control of parasites through rational drug design requires a thorough understanding of the parasite's lifecycle encompassing the biochemical and physiological processes which contribute to normal parasite homeostasis. The hatching of parasite eggs for example, represents an important process in the development of a parasitic infection. Previous studies in helminths have indicated that secreted enzymes often facilitate successful endoparasite egg hatch. In contrast, there are relatively few examples demonstrating a role for secreted enzymes in the egg hatching process of insects. An analysis of this process in the ectoparasite Lucilia cuprina suggests a role for secreted enzymes in the hatching of sheep blowfly eggs. Characterisation of the proteases collected at the time of egg hatch indicates the presence of serine proteases. Further purification and characterisation of these proteases may enable the design of specific inhibitors to interfere with the egg hatch process and therefore provide a novel means of control.

Introduction

The sheep blowfly is responsible for significant economic loss to both wool and meat producers in Australia, New Zealand and the United Kingdom. Over the years a number of control measures have been put in place which rely primarily on the use of insecticides to kill larvae in combination with management practices designed to make sheep less attractive to the blowfly[1]. While in the immediate future the strategic use of insecticides will continue to play an important role in sheep blowfly control, alternative approaches must be investigated in order to discover new generation products. Control through vaccination against the early stage larvae is currently under investigation2, 3. However, intervention in the lifecycle prior to larval infestation would result in zero or minimal damage to the host.

Flystrike infections are initiated when eggs are laid on the skin or in the wool of sheep. The eggs then mature over several hours as the embryo develops until the first stage larvae emerge. During this period the eggs are accessible to agents which may be able to disrupt the normal physiological processes which lead to egg hatch. The biochemical events involved in egg hatch of ectoparasites have not been extensively studied. In contrast, biochemical processes have been shown to be important in the hatching of a number of endoparasites. This review will therefore focus on the physical and biochemical mechanisms involved in egg hatch of both endoparasites and ectoparasites with particular reference to the sheep blowfly, Lucilia cuprina.

Section snippets

Mechanisms of hatching in endoparasitic helminths

The hatching of parasite eggs represents a critical phase in a parasite's lifecycle. The process of egg hatching has therefore been studied in considerable detail particularly as it relates to endoparasites. In general, the hatching process is initiated by an appropriate signal which may be provided by the host or environment. These environmental signals may stimulate the embryo to secrete compounds, for example enzymes, which then degrade the egg shell or cyst and thus facilitate hatch. The

Mechanisms of egg hatching in arthropod ectoparasites

In contrast to the hatching of endoparasite eggs, as described by Sikes and Wigglesworth[18]the mechanism of ectoparasite egg hatch has not been intensively studied apart from visual descriptions of the hatching process. These descriptions focus almost exclusively on the physical aspects of egg hatch and have in general not addressed the possibility that ES products may be important in this process.

The hatching of ectoparasites is believed to result from a combination of physical and

Control of egg hatch through rational drug design

The involvement of proteases in the egg hatch of L. cuprina provides the opportunity to investigate novel means for controlling the egg hatch process. Further characterisation of these proteases in terms of their tertiary structure may enable the design of specific inhibitors in order to block the egg hatch process. The use of specific protease inhibitors which are non-toxic to the host, but which display specificity for the target protease represents a novel approach to chemo therapy. Such an

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