Chitinolytic activity in nematodes and other parasites : a possible chemotherapeutic target
Chitin is present in the eggshells of Heligmosomoides polygyrus (5% of dry egg weight) and Caenorhabditis elegans. The chitinolytic activities from a number of parasite sources were examined by the use of a range of fluorometric substrates based on methylumbelliferyl glycosides. The chitinase inhibitor, allosamidin had varied effects on chitinolytic activities dependent on parasite source and substrate used. Nematode chitinases were the most sensitive with an IC50 of 2.2 nM for H. polygyrus eggs. Treatment with allosamidin slowed but did not prevent hatching of eggs of H.polygyrus. The nematode/bacterial complex, Heterorhabditis/ Xenorhabdus,showed chitinolytic activities and evidence from the use of allosamidin suggested that these were of bacterial origin. The baculovirus AcMNPV contained a single chitinase gene closely related to the Serratia marcescens chitinase A gene. The chitinase attacked both exo- and endochitinase substrates. A mutant constructed without the chitinase gene showed no chitinolytic activity above insect background. In vitro the mutant strain did not cause the massive cuticular breakdown associated with wild-type infection. This is the first viral chitinase reported. Chitinolytic activities were demonstrated Pneumocystis carinii (fungus) and Porocephalus crotali (pentastomid). No activity was located in procyclic forms of Trypanosoma bruceibrucei or the blood dwelling forms of Trypanosoma musculi. Chitinolytic activity was present in foetal calf serum which could explain a previous report of chitinolytic activity for procyclic forms of trypanosomes. The N-acetylglucosaminidase activities but not chitinase activities of the various parasites were inhibited by two synthetic analogues of N-acetylglucosamine.