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United States Department of Agriculture

Agricultural Research Service


item Rhoads, Marcia
item Fetterer, Raymond

Submitted to: Journal of Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Worms that infect livestock cause disease and economic losses estimated at over 500 million dollars annually. The effectiveness of drugs that are currently available for control of these diseases is limited because of cost and because drug resistance can occur. The lack of knowledge about basic biology of parasitic worms has hampered development of new control strategies. The current paper studies the characteristics of an enzyme secreted by the sheep stomach worm, Haemonchus contortus. These studies suggest that this enzyme helps the worm to move through the lining of the sheep's stomach and to break blood vessels to gain the nutrients needed for its survival. The inactivation of this enzyme may provide the basis for development of new controls.

Technical Abstract: To better understand the in vivo function of the secreted cysteine protease of Haemonchus contortus, the ability of live parasites to degrade connective tissue was investigated using [3H]proline-labeled extracellular matrix produced by smooth-muscle cells (R22). The matrix was composed of glycoprotein(s) 34%, elastin (49%) and collagen (15%) in an insoluble, multi-layered, cross-linked structure. No degradation of the extracellular matrix by third-stage larave (L3)(10,000/ml) occurred during 24-hr in vitro incubation. In contrast, fourth-stage larvae (L4)(1,000/ml) degraded 42% of the matrix while adults (100/ml) degraded the entire matrix. Adults, maintained in the presence of a metabolic inhibitor, rafoxanide (100 M), were non-motile and matrix degradation was reduced to 19%. The presence of Z-phe-ala-FMK (100 M), a specific cysteine protease inhibitor, reduced matrix degradation to 30% without affecting parasite motility. Isolated adult excretory/secretory products (ESP) (0.1 mg protein/ml) degraded 64% of the total matrix; specific degradation consisted of 80.3% of the glycoprotein, 67.1% of the elastin, and 27.6% of the collagen matrix components. Degradation of the matrix by ESP was stimulated by dithiothreitol (DTT) (2 mM) and inhibited by Z-phe-ala-FMK. Thus the secretory cysteine protease of H. contortus is active under physiologic conditions and able to degrade the major components of connective tissue in an in vitro model system that simulates their structure in vivo. These data strengthen the proposed role of this enzyme in the breakdown of host tissue.

Last Modified: 07/20/2017
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