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A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts

Naegleria fowleri is a free-living amoeba that is ubiquitous in diverse natural environments. It causes a fatal brain infection in humans known as primary amoebic meningoencephalitis. Despite the medical importance of the parasitic disease, there is a great lack of knowledge about the biology and pa...

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Autores principales: Lê, Hương Giang, Ham, A-Jeong, Kang, Jung-Mi, Võ, Tuấn Cường, Naw, Haung, Sohn, Hae-Jin, Shin, Ho-Joon, Na, Byoung-Kuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063937/
https://www.ncbi.nlm.nih.gov/pubmed/33804993
http://dx.doi.org/10.3390/pathogens10040388
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author Lê, Hương Giang
Ham, A-Jeong
Kang, Jung-Mi
Võ, Tuấn Cường
Naw, Haung
Sohn, Hae-Jin
Shin, Ho-Joon
Na, Byoung-Kuk
author_facet Lê, Hương Giang
Ham, A-Jeong
Kang, Jung-Mi
Võ, Tuấn Cường
Naw, Haung
Sohn, Hae-Jin
Shin, Ho-Joon
Na, Byoung-Kuk
author_sort Lê, Hương Giang
collection PubMed
description Naegleria fowleri is a free-living amoeba that is ubiquitous in diverse natural environments. It causes a fatal brain infection in humans known as primary amoebic meningoencephalitis. Despite the medical importance of the parasitic disease, there is a great lack of knowledge about the biology and pathogenicity of N. fowleri. In this study, we identified and characterized a novel cysteine protease inhibitor of N. fowleri (NfCPI). NfCPI is a typical cysteine protease inhibitor belonging to the cystatin family with a Gln-Val-Val-Ala-Gly (QVVAG) motif, a characteristic motif conserved in the cystatin family of proteins. Bacterially expressed recombinant NfCPI has a dimeric structure and exhibits inhibitory activity against several cysteine proteases including cathespin Bs of N. fowleri at a broad range of pH values. Expression profiles of nfcpi revealed that the gene was highly expressed during encystation and cyst of the amoeba. Western blot and immunofluorescence assays also support its high level of expression in cysts. These findings collectively suggest that NfCPI may play a critical role in encystation or cyst formation of N. fowleri by regulating cysteine proteases that may mediate encystation or mature cyst formation of the amoeba. More comprehensive studies to investigate the roles of NfCPI in encystation and its target proteases are necessary to elucidate the regulatory mechanism and the biological significance of NfCPI.
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spelling pubmed-80639372021-04-24 A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts Lê, Hương Giang Ham, A-Jeong Kang, Jung-Mi Võ, Tuấn Cường Naw, Haung Sohn, Hae-Jin Shin, Ho-Joon Na, Byoung-Kuk Pathogens Article Naegleria fowleri is a free-living amoeba that is ubiquitous in diverse natural environments. It causes a fatal brain infection in humans known as primary amoebic meningoencephalitis. Despite the medical importance of the parasitic disease, there is a great lack of knowledge about the biology and pathogenicity of N. fowleri. In this study, we identified and characterized a novel cysteine protease inhibitor of N. fowleri (NfCPI). NfCPI is a typical cysteine protease inhibitor belonging to the cystatin family with a Gln-Val-Val-Ala-Gly (QVVAG) motif, a characteristic motif conserved in the cystatin family of proteins. Bacterially expressed recombinant NfCPI has a dimeric structure and exhibits inhibitory activity against several cysteine proteases including cathespin Bs of N. fowleri at a broad range of pH values. Expression profiles of nfcpi revealed that the gene was highly expressed during encystation and cyst of the amoeba. Western blot and immunofluorescence assays also support its high level of expression in cysts. These findings collectively suggest that NfCPI may play a critical role in encystation or cyst formation of N. fowleri by regulating cysteine proteases that may mediate encystation or mature cyst formation of the amoeba. More comprehensive studies to investigate the roles of NfCPI in encystation and its target proteases are necessary to elucidate the regulatory mechanism and the biological significance of NfCPI. MDPI 2021-03-24 /pmc/articles/PMC8063937/ /pubmed/33804993 http://dx.doi.org/10.3390/pathogens10040388 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Lê, Hương Giang
Ham, A-Jeong
Kang, Jung-Mi
Võ, Tuấn Cường
Naw, Haung
Sohn, Hae-Jin
Shin, Ho-Joon
Na, Byoung-Kuk
A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title_full A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title_fullStr A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title_full_unstemmed A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title_short A Novel Cysteine Protease Inhibitor of Naegleria fowleri That Is Specifically Expressed during Encystation and at Mature Cysts
title_sort novel cysteine protease inhibitor of naegleria fowleri that is specifically expressed during encystation and at mature cysts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063937/
https://www.ncbi.nlm.nih.gov/pubmed/33804993
http://dx.doi.org/10.3390/pathogens10040388
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