A Proteomic and Functional Study of the Schistosoma mansoni Egg

Newly released eggs ofthe parasitic wonn Schistosoma mansoni either pass
through the gut wall to escape from the host or are washed away in the host's
bloodstream. In the latte~ scenario most eggs become lodged in ihe host's liver,
where they become the focus ofa granulomatous response which can have
severe pathological consequences. In this study, the S. mansoni soluble egg
proteome is described and characterised for the first time. Mature eggs were
separated from immature eggs and then fractionated into their morphological
components: the miracidia, the hatch fluid (which bathes the miracidia) and the
egg-secreted proteins. Each egg preparation was subjected to two-dimensional
electrophoresis and tandem mass spectrometry. Developmental proteomic
changes were then described in tenns ofthe egg's morphology so insights into
the egg's natural history were gained. For example, acquisition of aerobic
respiratory enzymes by the miracidium was seen, but nevertheless the
miracidium still favours the use of energy-efficient heat shock proteins. Western
blotting was used to show that the immature egg adopts the ubiquitin-
--proteasome pathway to degrade its nutritive vitelline cells. The hatch fluid
contains host proteins but it also has a defensive role, although its most
abundant constituent (a large, acidic glycoprotein) is ofunknown function. The
egg-secreted proteins consist ofdifferent variants ofjust four proteins, one of
which has a pro-protein convertase domain and another of which appears to be a
general purpose binding protein. A protocol is devised to pmi[y ea~h variant, so
further functional studies into the individual secreted proteins can be carried out
in the futur~. The secreted proteins induce a profound proliferative response in
lymphocytes from acutely infected mice, indicating that they may work by
activating granuloma T cells to secrete pro-proteases that are subsequently
activated, enabling the egg to cross the gut wall.