TRANSGLUTAMINASE-CATALYZED INCORPORATION OF HOST PROTEINS IN BRUGIA-MALAYI MICROFILARIAE

Recently, we have characterized and purified a novel transglutaminase (pTGase) from adults of the filarial worms Brugia malayi, pTGase-catal yzed reactions seem to play an essential role during in utero growth a nd development of microfilariae. The results presented here demonstrat e that exudates from the peritoneal cavity of jirds, the site where ad ult worms of B. malayi reside and produce microfilariae, contain sever al host proteins that can serve as substrates in pTGase-catalyzed reac tions. The peritoneal exudate proteins are avidly taken up by adult fe male worms in vitro and incorporated into the developing microfilariae . Among the several host proteins that were crosslinked, a 68-kDa mole cular weight protein (p68) was found to be the major protein taken up by the parasites. Following uptake by the parasites, the peritoneal ex udate proteins are crosslinked to form high molecular weight aggregate s, that are subsequently incorporated into in utero developing embryos and microfilariae. The cross-linking of host proteins was, however, i nhibited by monodansylcadaverine (MDC), a competitive inhibitor of pTG ase. Antibodies raised against the jird peritoneal exudate proteins st rongly immunoreacted with a 68-kDa protein in adult worms and microfil ariae extracts but not with infective-stage larvae (L(3)) of B. malayi . These results suggest that pTGase is involved in covalent incorporat ion of host proteins (such as p68) into developing embryos and microfi lariae of B. malayi.