<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli

<p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Andersen Kasper [verfasserIn] Marcotte Harold [verfasserIn] Álvarez Beatriz [verfasserIn] Boyaka Prosper N [verfasserIn] Hammarström Lennart [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2011

Übergeordnetes Werk:	In: BMC Biotechnology - BMC, 2003, 11(2011), 1, p 126
Übergeordnetes Werk:	volume:11 ; year:2011 ; number:1, p 126

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1472-6750-11-126

Katalog-ID:	DOAJ064070484

Internformat


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520			\|a <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p<
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912			\|a GBV_ILN_2190
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912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
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Indexfelder

author_variant	a k ak m h mh á b áb b p n bpn h l hl
matchkey_str	article:14726750:2011----::tniutatonetnlrtcingisatrxdmtxnyigehiatbd
hierarchy_sort_str	2011
callnumber-subject-code	TP
publishDate	2011
allfields	10.1186/1472-6750-11-126 doi (DE-627)DOAJ064070484 (DE-599)DOAJca38540deff24ee5982687b1a975bf0d DE-627 ger DE-627 rakwb eng TP248.13-248.65 Andersen Kasper verfasserin aut <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Biotechnology Marcotte Harold verfasserin aut Álvarez Beatriz verfasserin aut Boyaka Prosper N verfasserin aut Hammarström Lennart verfasserin aut In BMC Biotechnology BMC, 2003 11(2011), 1, p 126 (DE-627)332164837 (DE-600)2052746-9 14726750 nnns volume:11 year:2011 number:1, p 126 https://doi.org/10.1186/1472-6750-11-126 kostenfrei https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d kostenfrei http://www.biomedcentral.com/1472-6750/11/126 kostenfrei https://doaj.org/toc/1472-6750 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2011 1, p 126
spelling	10.1186/1472-6750-11-126 doi (DE-627)DOAJ064070484 (DE-599)DOAJca38540deff24ee5982687b1a975bf0d DE-627 ger DE-627 rakwb eng TP248.13-248.65 Andersen Kasper verfasserin aut <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Biotechnology Marcotte Harold verfasserin aut Álvarez Beatriz verfasserin aut Boyaka Prosper N verfasserin aut Hammarström Lennart verfasserin aut In BMC Biotechnology BMC, 2003 11(2011), 1, p 126 (DE-627)332164837 (DE-600)2052746-9 14726750 nnns volume:11 year:2011 number:1, p 126 https://doi.org/10.1186/1472-6750-11-126 kostenfrei https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d kostenfrei http://www.biomedcentral.com/1472-6750/11/126 kostenfrei https://doaj.org/toc/1472-6750 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2011 1, p 126
allfields_unstemmed	10.1186/1472-6750-11-126 doi (DE-627)DOAJ064070484 (DE-599)DOAJca38540deff24ee5982687b1a975bf0d DE-627 ger DE-627 rakwb eng TP248.13-248.65 Andersen Kasper verfasserin aut <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Biotechnology Marcotte Harold verfasserin aut Álvarez Beatriz verfasserin aut Boyaka Prosper N verfasserin aut Hammarström Lennart verfasserin aut In BMC Biotechnology BMC, 2003 11(2011), 1, p 126 (DE-627)332164837 (DE-600)2052746-9 14726750 nnns volume:11 year:2011 number:1, p 126 https://doi.org/10.1186/1472-6750-11-126 kostenfrei https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d kostenfrei http://www.biomedcentral.com/1472-6750/11/126 kostenfrei https://doaj.org/toc/1472-6750 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2011 1, p 126
allfieldsGer	10.1186/1472-6750-11-126 doi (DE-627)DOAJ064070484 (DE-599)DOAJca38540deff24ee5982687b1a975bf0d DE-627 ger DE-627 rakwb eng TP248.13-248.65 Andersen Kasper verfasserin aut <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Biotechnology Marcotte Harold verfasserin aut Álvarez Beatriz verfasserin aut Boyaka Prosper N verfasserin aut Hammarström Lennart verfasserin aut In BMC Biotechnology BMC, 2003 11(2011), 1, p 126 (DE-627)332164837 (DE-600)2052746-9 14726750 nnns volume:11 year:2011 number:1, p 126 https://doi.org/10.1186/1472-6750-11-126 kostenfrei https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d kostenfrei http://www.biomedcentral.com/1472-6750/11/126 kostenfrei https://doaj.org/toc/1472-6750 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2011 1, p 126
allfieldsSound	10.1186/1472-6750-11-126 doi (DE-627)DOAJ064070484 (DE-599)DOAJca38540deff24ee5982687b1a975bf0d DE-627 ger DE-627 rakwb eng TP248.13-248.65 Andersen Kasper verfasserin aut <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p< Biotechnology Marcotte Harold verfasserin aut Álvarez Beatriz verfasserin aut Boyaka Prosper N verfasserin aut Hammarström Lennart verfasserin aut In BMC Biotechnology BMC, 2003 11(2011), 1, p 126 (DE-627)332164837 (DE-600)2052746-9 14726750 nnns volume:11 year:2011 number:1, p 126 https://doi.org/10.1186/1472-6750-11-126 kostenfrei https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d kostenfrei http://www.biomedcentral.com/1472-6750/11/126 kostenfrei https://doaj.org/toc/1472-6750 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2119 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2011 1, p 126
language	English
source	In BMC Biotechnology 11(2011), 1, p 126 volume:11 year:2011 number:1, p 126
sourceStr	In BMC Biotechnology 11(2011), 1, p 126 volume:11 year:2011 number:1, p 126
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Biotechnology
isfreeaccess_bool	true
container_title	BMC Biotechnology
authorswithroles_txt_mv	Andersen Kasper @@aut@@ Marcotte Harold @@aut@@ Álvarez Beatriz @@aut@@ Boyaka Prosper N @@aut@@ Hammarström Lennart @@aut@@
publishDateDaySort_date	2011-01-01T00:00:00Z
hierarchy_top_id	332164837
id	DOAJ064070484
language_de	englisch
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callnumber-first	T - Technology
author	Andersen Kasper
spellingShingle	Andersen Kasper misc TP248.13-248.65 misc Biotechnology <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
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topic_title	TP248.13-248.65 <it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
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title	<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
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title_full	<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
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author_browse	Andersen Kasper Marcotte Harold Álvarez Beatriz Boyaka Prosper N Hammarström Lennart
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title_sort	<it<in situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
callnumber	TP248.13-248.65
title_auth	<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
abstract	<p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p<
abstractGer	<p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p<
abstract_unstemmed	<p/< <p<Background</p< <p<Anthrax is caused by the bacterium <it<Bacillus anthracis </it<and is regarded as one of the most prominent bioterrorism threats. Anthrax toxicity is induced by the tripartite toxin complex, composed of the receptor-binding anthrax protective antigen and the two enzymatic subunits, lethal factor and edema factor. Recombinant lactobacilli have previously been used to deliver antibody fragments directed against surface epitopes of a variety of pathogens, including <it<Streptococcus mutans, Porphyromonas gingivalis</it<, and rotavirus. Here, we addressed whether or not anthrax toxins could be targeted and neutralised in the gastrointestinal tract by lactobacilli producing recombinant antibody fragments as a model system for toxin neutralisation in the gastrointestinal lumen.</p< <p<Results</p< <p<The neutralising anti-PA scFv, 1H, was expressed in <it<L. paracasei </it<as a secreted protein, a cell wall-anchored protein or both secreted and wall-anchored protein. Cell wall display on lactobacilli and PA binding of the anchored constructs was confirmed by flow cytometry analysis. Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. The ability of lactobacilli to colonise the gastrointestinal tract may allow the system to be used both prophylactically and therapeutically.</p<
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title_short	<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
url	https://doi.org/10.1186/1472-6750-11-126 https://doaj.org/article/ca38540deff24ee5982687b1a975bf0d http://www.biomedcentral.com/1472-6750/11/126 https://doaj.org/toc/1472-6750
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Binding of secreted or attached scFv produced by lactobacilli to PA were verified by ELISA. Both construct were able to protect macrophages in an <it<in vitro </it<cytotoxicity assay. Finally, lactobacilli producing the cell wall attached scFv were able to neutralise the activity of anthrax edema toxin in the GI tract of mice, <it<in vivo</it<.</p< <p<Conclusion</p< <p<We have developed lactobacilli expressing a neutralising scFv fragment against the PA antigen of the anthrax toxin, which can provide protection against anthrax toxins both <it<in vitro </it<and <it<in vivo</it<. Utilising engineered lactobacilli therapeutically for neutralising toxins in the gastrointestinal tract can potential be expanded to provide protection against a range of additional gastrointestinal pathogens. 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<it<In situ </it<gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli

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