Cloning and Characterization of Two Potent Kunitz Type Protease Inhibitors from Echinococcus granulosus

Ranasinghe, Shiwanthi L., Fischer, Katja, Zhang, Wenbao, Gobert, Geoffrey N. and McManus, Donald P. (2015) Cloning and Characterization of Two Potent Kunitz Type Protease Inhibitors from Echinococcus granulosus. PLoS Neglected Tropical Diseases, 9 12: . doi:10.1371/journal.pntd.0004268

Author Ranasinghe, Shiwanthi L.
Fischer, Katja
Zhang, Wenbao
Gobert, Geoffrey N.
McManus, Donald P.
Title Cloning and Characterization of Two Potent Kunitz Type Protease Inhibitors from Echinococcus granulosus
Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2735
Publication date 2015-12-08
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0004268
Open Access Status DOI
Volume 9
Issue 12
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2016
Language eng
Formatted abstract
The tapeworm Echinococcus granulosus is responsible for cystic echinococcosis (CE), a cosmopolitan disease which imposes a significant burden on the health and economy of affected communities. Little is known about the molecular mechanisms whereby E. granulosus is able to survive in the hostile mammalian host environment, avoiding attack by host enzymes and evading immune responses, but protease inhibitors released by the parasite are likely implicated. We identified two nucleotide sequences corresponding to secreted single domain Kunitz type protease inhibitors (EgKIs) in the E. granulosus genome, and their cDNAs were cloned, bacterially expressed and purified. EgKI-1 is highly expressed in the oncosphere (egg) stage and is a potent chymotrypsin and neutrophil elastase inhibitor that binds calcium and reduced neutrophil infiltration in a local inflammation model. EgKI-2 is highly expressed in adult worms and is a potent inhibitor of trypsin. As powerful inhibitors of mammalian intestinal proteases, the EgKIs may play a pivotal protective role in preventing proteolytic enzyme attack thereby ensuring survival of E. granulosus within its mammalian hosts. EgKI-1 may also be involved in the oncosphere in host immune evasion by inhibiting neutrophil elastase and cathepsin G once this stage is exposed to the mammalian blood system. In light of their key roles in protecting E. granulosus from host enzymatic attack, the EgKI proteins represent potential intervention targets to control CE. This is important as new public health measures against CE are required, given the inefficiencies of available drugs and the current difficulties in its treatment and control. In addition, being a small sized highly potent serine protease inhibitor, and an inhibitor of neutrophil chemotaxis, EgKI-1 may have clinical potential as a novel anti-inflammatory therapeutic.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Public Health Publications
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