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-catalyzed reactions seem to play an essential role during in utero growth and development of microfilariae. The results presented here demonstrate that exudates from the peritoneal cavity of jirds, the site where adult worms of B. malayi reside and produce microfilariae, contain several host proteins that can serve as substrates in pTGase-catalyzed reactions. The peritoneal exudate proteins are avidly taken up by adult female worms in vitro and incorporated into the developing microfilariae. Among the several host proteins that were crosslinked, a 68-kDa molecular weight protein (p68) was found to be the major protein taken up by the parasites. Following uptake by the parasites, the peritoneal exudate proteins are crosslinked to form high molecular weight aggregates, that are subsequently incorporated into in utero developing embryos and microfilariae. The cross-linking of host proteins was, however, inhibited by monodansylcadaverine (MDC), a competitive inhibitor of pTGase. Antibodies raised against the jird peritoneal exudate proteins strongly immunoreacted with a 68-kDa protein in adult worms and microfilariae extracts but not with infective-stage larvae (L3) of B. malayi. These results suggest that pTGase is involved in covalent incorporation of host proteins (such as p68) into developing embryos and microfilariae of B. malayi.
Mehta
K
K
Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. kapil-mehta@isqm.mda.uth.tmc.edu
Chandrashekar
R
R
Rao
U R
UR
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism / Q000469:parasitology; D015153:Blotting, Western; D017178:Brugia malayi / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology*; D002103:Cadaverine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005849:Gerbillinae / Q000378:metabolism / Q000469:parasitology*; D006790:Host-Parasite Interactions; D008842:Microfilariae / Q000201:enzymology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015800:Protozoan Proteins / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism*
D015800:Protozoan Proteins; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine