Proteinases as Drug Targets
Chapter 8: Blood-Feeding Human Hookworm Proteases
Published:22 Nov 2011
Special Collection: 2011 ebook collection , 2011 ebook collection , 2011-2015 organic chemistry subject collectionSeries: Drug Discovery
A. Loukas, N. Ranjit, D. A. Pickering, and M. S. Pearson, in Proteinases as Drug Targets, ed. B. Dunn, The Royal Society of Chemistry, 2011, ch. 8, pp. 186-198.
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Proteases are pivotal to parasitism, mediating biological processes crucial to the survival of parasitic helminth (worms). Hookworms live in the small intestine of their mammalian hosts, and bury their anterior ends under the mucosa where they rupture the capillaries and feed on the extravasated blood. A suite of proteases are expressed in the intestine of the hookworm, where they act to degrade host hemoglobin and serum proteins as part of the feeding process. These proteases are exposed to components of the host's immune system when the worms ingest blood, and therefore present as targets for the development of anti-helminth vaccines and prophylactic drugs. The protective effects of current vaccine antigens against hookworms and related nematodes of livestock (barber's pole worm) are based on hemoglobin-degrading intestinal proteases and act largely due to the neutralization of these proteases by antibodies that are ingested with the blood meal. In this chapter, we survey the current status of hookworm and proteases that show promise as vaccines and describe their vital contribution to a parasitic existence.