Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone

ABSTRACT Cysteine peptidases (CPs) of Entamoeba histolytica are considered to be important pathogenicity factors. Previous studies have found that under standard axenic culture conditions, only four (ehcp-a1, ehcp-a2, ehcp-a5, and ehcp-a7) out of 35 papain-like ehcp genes present in the E. histolyti...

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Autores principales:	Jenny Matthiesen, Ann-Katrein Bär, Anne-Kathrin Bartels, Dennis Marien, Susann Ofori, Laura Biller, Egbert Tannich, Hannelore Lotter, Iris Bruchhaus
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e9d0e7a4fcf1405daf364ffa9d4da5f1
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spelling	oai:doaj.org-article:e9d0e7a4fcf1405daf364ffa9d4da5f12021-11-15T15:40:29ZOverexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone10.1128/mBio.00072-132150-7511https://doaj.org/article/e9d0e7a4fcf1405daf364ffa9d4da5f12013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00072-13https://doaj.org/toc/2150-7511ABSTRACT Cysteine peptidases (CPs) of Entamoeba histolytica are considered to be important pathogenicity factors. Previous studies have found that under standard axenic culture conditions, only four (ehcp-a1, ehcp-a2, ehcp-a5, and ehcp-a7) out of 35 papain-like ehcp genes present in the E. histolytica genome are expressed at high levels. Little is known about the expression of CPs in E. histolytica during amoebic liver abscess (ALA) formation. In the current study, a quantitative real-time PCR assay was developed to determine the expression of the various ehcp genes during ALA formation in animal models. Increased expression of four ehcp genes (ehcp-a3, -a4, -a10, and -c13) was detected in the gerbil and mouse models. Increased expression of another three ehcp genes (ehcp-a5, -a6, and -a7) was detected in the mouse model only, and two other ehcp genes (ehcp-b8 and -b9) showed increased expression in the gerbil model only. Trophozoites of the nonpathogenic E. histolytica HM-1:IMSS clone A1, which was unable to induce ALAs, were transfected with vectors enabling overexpression of those CPs that are expressed at high levels under culture conditions or during ALA formation. Interestingly, overexpression of ehcp-b8, -b9, and -c13 restored the pathogenic phenotype of the nonpathogenic clone A1 whereas overexpression of various other peptidase genes had no effect on the pathogenicity of this clone. IMPORTANCE Entamoeba histolytica is a widespread and clinically important protozoan parasite. It normally exists in the human intestine without causing clinical symptoms but can invade the intestinal mucosa, which causes serious intestinal (amoebic colitis) and extraintestinal (amoebic liver abscess [ALA]) diseases. The identification of factors responsible for the invasion of the parasite and disease formation is a major topic in the field. Here, we investigate the roles of different papain-like cysteine peptidases (CPs) as pathogenicity factors. We show that the expression of some of the peptidases that are normally expressed at low levels increases during ALA formation. Furthermore, nonpathogenic amoebae can be transformed to pathogenic amoebae, simply by specific overexpression of some of these CPs. Our findings reinforce the importance of CPs as pathogenicity factors of E. histolytica.Jenny MatthiesenAnn-Katrein BärAnne-Kathrin BartelsDennis MarienSusann OforiLaura BillerEgbert TannichHannelore LotterIris BruchhausAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jenny Matthiesen Ann-Katrein Bär Anne-Kathrin Bartels Dennis Marien Susann Ofori Laura Biller Egbert Tannich Hannelore Lotter Iris Bruchhaus Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
description	ABSTRACT Cysteine peptidases (CPs) of Entamoeba histolytica are considered to be important pathogenicity factors. Previous studies have found that under standard axenic culture conditions, only four (ehcp-a1, ehcp-a2, ehcp-a5, and ehcp-a7) out of 35 papain-like ehcp genes present in the E. histolytica genome are expressed at high levels. Little is known about the expression of CPs in E. histolytica during amoebic liver abscess (ALA) formation. In the current study, a quantitative real-time PCR assay was developed to determine the expression of the various ehcp genes during ALA formation in animal models. Increased expression of four ehcp genes (ehcp-a3, -a4, -a10, and -c13) was detected in the gerbil and mouse models. Increased expression of another three ehcp genes (ehcp-a5, -a6, and -a7) was detected in the mouse model only, and two other ehcp genes (ehcp-b8 and -b9) showed increased expression in the gerbil model only. Trophozoites of the nonpathogenic E. histolytica HM-1:IMSS clone A1, which was unable to induce ALAs, were transfected with vectors enabling overexpression of those CPs that are expressed at high levels under culture conditions or during ALA formation. Interestingly, overexpression of ehcp-b8, -b9, and -c13 restored the pathogenic phenotype of the nonpathogenic clone A1 whereas overexpression of various other peptidase genes had no effect on the pathogenicity of this clone. IMPORTANCE Entamoeba histolytica is a widespread and clinically important protozoan parasite. It normally exists in the human intestine without causing clinical symptoms but can invade the intestinal mucosa, which causes serious intestinal (amoebic colitis) and extraintestinal (amoebic liver abscess [ALA]) diseases. The identification of factors responsible for the invasion of the parasite and disease formation is a major topic in the field. Here, we investigate the roles of different papain-like cysteine peptidases (CPs) as pathogenicity factors. We show that the expression of some of the peptidases that are normally expressed at low levels increases during ALA formation. Furthermore, nonpathogenic amoebae can be transformed to pathogenic amoebae, simply by specific overexpression of some of these CPs. Our findings reinforce the importance of CPs as pathogenicity factors of E. histolytica.
format	article
author	Jenny Matthiesen Ann-Katrein Bär Anne-Kathrin Bartels Dennis Marien Susann Ofori Laura Biller Egbert Tannich Hannelore Lotter Iris Bruchhaus
author_facet	Jenny Matthiesen Ann-Katrein Bär Anne-Kathrin Bartels Dennis Marien Susann Ofori Laura Biller Egbert Tannich Hannelore Lotter Iris Bruchhaus
author_sort	Jenny Matthiesen
title	Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
title_short	Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
title_full	Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
title_fullStr	Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
title_full_unstemmed	Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone
title_sort	overexpression of specific cysteine peptidases confers pathogenicity to a nonpathogenic <named-content content-type="genus-species">entamoeba histolytica</named-content> clone
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/e9d0e7a4fcf1405daf364ffa9d4da5f1
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Overexpression of Specific Cysteine Peptidases Confers Pathogenicity to a Nonpathogenic <named-content content-type="genus-species">Entamoeba histolytica</named-content> Clone

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