Serine proteinase inhibitors from nematodes and the arms race between host and pathogen

Abstract

Parasite nematode genomics is a relatively new field9, but already two of the most interesting gene families to be found encode serine proteinase inhibitors. This article describes a family of nematode proteinase inhibitors with homology to mammalian serpins, as well as a distinct set of lower-molecularweight inhibitors first discovered by biochemical analysis of the human roundworm Ascaris10.Taking these two examples into account, it thus appears that parasitic nematodes have evolved two parallel strategies for interfering with mammalian serine Serine proteinase inhibitors are encoded by a large gene family of long evolutionary standing. Recent discoveries of parasite proteins that inhibit human serine proteinases, together with the complete genomic sequence from Caenorhabditis elegans, have provided a set of new serine proteinase inhibitors from more primitive metazoan animals such as nematodes. The structural features (e.g. reactive centre residues), gene organization (including intron arrangements) and inhibitory function and targets (e.g. inflammatory and coagulation pathway proteinase) all contribute important new insights into proteinase inhibitor evolution. Some parasite products have evolved that block enzymes in the mammalian host, but the human host responds with a significant immune response to the parasite inhibitors. Thus, infection produces a finely balanced conflict between host and pathogen at the molecular level, and this might have accelerated the evolution of these proteins in parasitic species as well as their hosts.