The Zoonotic Helminth Parasite Fasciola hepatica: Virulence-Associated Cathepsin B and Cathepsin L Cysteine Peptidases Secreted by Infective Newly Excysted Juveniles (NEJ).

Barbour, Tara, Cwiklinski, Krystyna ORCID: 0000-0001-5577-2735, Lalor, Richard ORCID: 0000-0003-0433-9805, Dalton, John Pius ORCID: 0000-0003-3829-9186 and De Marco Verissimo, Carolina (2021) The Zoonotic Helminth Parasite Fasciola hepatica: Virulence-Associated Cathepsin B and Cathepsin L Cysteine Peptidases Secreted by Infective Newly Excysted Juveniles (NEJ). Animals : an open access journal from MDPI, 11 (12). 3495-.

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Official URL: http://dx.doi.org/10.3390/ani11123495

Abstract

Fasciolosis caused by Fasciola hepatica is a major global disease of livestock and an important neglected helminthiasis of humans. Infection arises when encysted metacercariae are ingested by the mammalian host. Within the intestine, the parasite excysts as a newly excysted juvenile (NEJ) that penetrates the intestinal wall and migrates to the liver. NEJ excystment and tissue penetration are facilitated by the secretion of cysteine peptidases, namely, cathepsin B1 (FhCB1), cathepsin B2 (FhCB2), cathepsin B3 (FhCB3) and cathepsin L3 (FhCL3). While our knowledge of these peptidases is growing, we have yet to understand why multiple enzymes are required for parasite invasion. Here, we produced functional recombinant forms of these four peptidases and compared their physio-biochemical characteristics. Our studies show great variation of their pH optima for activity, substrate specificity and inhibitory profile. Carboxy-dipeptidase activity was exhibited exclusively by FhCB1. Our studies suggest that, combined, these peptidases create a powerful hydrolytic cocktail capable of digesting the various host tissues, cells and macromolecules. Although we found several inhibitors of these enzymes, they did not show potent inhibition of metacercarial excystment or NEJ viability in vitro. However, this does not exclude these peptidases as targets for future drug or vaccine development.

Item Type:	Article
Uncontrolled Keywords:	Fasciola hepatica, cathepsin B, cathepsin L, cysteine peptidases, drug targets, flatworm, liver fluke, parasites, trematode, vaccines
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	24 Feb 2022 09:37
Last Modified:	14 Mar 2024 17:46
DOI:	10.3390/ani11123495
Open Access URL:	https://www.mdpi.com/2076-2615/11/12/3495
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3149563