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Hookworm cathepsin D aspartic proteases: contributing roles in the host-specific degradation of serum proteins and skin macromolecules

Published online by Cambridge University Press:  24 April 2003

A. L. WILLIAMSON
Affiliation:
The Queensland Institute of Medical Research and Department of Microbiology and Tropical Medicine, The University of Queensland, Brisbane, Queensland, Australia Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, Washington DC, USA
P. J. BRINDLEY
Affiliation:
Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA
A. LOUKAS
Affiliation:
The Queensland Institute of Medical Research and Department of Microbiology and Tropical Medicine, The University of Queensland, Brisbane, Queensland, Australia Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, Washington DC, USA

Abstract

Cathepsin D aspartic proteases of hookworms were recently implicated in the host-specific digestion of haemoglobin by adult parasites. Ac-APR-1 from the dog hookworm, Ancylostoma caninum and Na-APR-1 from the human hookworm, Necator americanus, were shown to be expressed in the infective larval stage (L3) as well as adult worms. We now show that both proteases degraded skin macromolecules and serum proteins, some of which were cleaved more readily from permissive definitive hosts as opposed to non-permissive hosts. Na-APR-1 degraded human collagens more efficiently than did Ac-APR-1, and Ac-APR-1 degraded canine serum albumin more efficiently than did Na-APR-1. On the other hand, both enzymes degraded human serum proteins (albumin and fibrinogen) with approximately equal efficiency under the conditions of our assays in vitro. Molecular models of these 2 orthologous, aspartic proteases showed that, despite having active site clefts with identical primary sequences, residues in the S3 pocket adopted different conformations, likely accounting for different substrate preferences reported previously. Antisera raised to both proteases partially inhibited (16–26%) migration of hookworm L3 through hamster skin in vitro, further implying a connective tissue invasive role for these enzymes in addition to digestion of serum and erythrocyte proteins for nutrition.

Type
Research Article
Copyright
2003 Cambridge University Press

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