Cysteine proteases as digestive enzymes in parasitic helminths.

Conor R Caffrey,David Smith,John P Dalton,Louise Goupil,Karina M Rebello,Aaron R Jex

doi:10.1371/journal.pntd.0005840

Abstract

We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1–4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].

Highlights

We briefly review cysteine proteases that are expressed in flatworm and nematode parasites
The two most prevalent hookworm species infecting humans are Necator americanus and Ancylostoma duodenale, with A. ceylanicum being found in certain areas [16, 17]
A cysteine protease similar to cathepsin B was subsequently characterized in adult T. suis gut extracts and excretory/secretory products (ESP) using both fluorogenic peptide substrates and protein substrate gels [40]

Summary

Cysteine proteases as digestive enzymes in parasitic helminths

OPEN ACCESS Citation: Caffrey CR, Goupil L, Rebello KM, Dalton JP, Smith D (2018) Cysteine proteases as digestive enzymes in parasitic helminths. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1,2,3,4]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].

Hookworm and Haemonchus

Trichuris and Ascaris

Cathepsin L Cathepsin L Cathepsin L and B

Key Learning Points

Findings

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