Bacteriophages as Pathogens and Immune Modulators?

ABSTRACT While Shiga toxins (Stx) are key determinants of enterohemorrhagic Escherichia coli (EHEC) pathophysiology in humans, their dissemination to target organs following gastrointestinal EHEC infection is still poorly understood. Most types of Stx target cells with globotriaosylceramide (Gb3) re...

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Autores principales:	A. Lengeling, A. Mahajan, D. L. Gally
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5e803fd52abb47aaa8c08be7aa7ee07d
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spelling	oai:doaj.org-article:5e803fd52abb47aaa8c08be7aa7ee07d2021-11-15T15:42:32ZBacteriophages as Pathogens and Immune Modulators?10.1128/mBio.00868-132150-7511https://doaj.org/article/5e803fd52abb47aaa8c08be7aa7ee07d2013-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00868-13https://doaj.org/toc/2150-7511ABSTRACT While Shiga toxins (Stx) are key determinants of enterohemorrhagic Escherichia coli (EHEC) pathophysiology in humans, their dissemination to target organs following gastrointestinal EHEC infection is still poorly understood. Most types of Stx target cells with globotriaosylceramide (Gb3) receptors, which are expressed on endothelial cells. According to current theory, Stx is trafficked on the surface of peripheral blood cells, and transfer of toxin from these trafficking cells to endothelial cells results in microvascular damage to target organs, including the kidneys and brain. Inside the cell, Stx inhibits protein synthesis, resulting in cell death. Host “repair” responses can lead to microthrombus formation, erythrocyte damage, and reduced oxygen supply, potentially resulting in organ failure. A recent study [L. V. Bentancor et al., mBio 4(5):e00501-13, 2013, doi:10.1128/mBio.00501-13] indicates that another mechanism for Stx “dissemination” needs to be considered. Bentancor et al. demonstrated that high-pressure injection of a plasmid encoding the “prokaryotic” Stx2 sequence into mice can lead to mortality, with pathology indicative of Stx activity and antibody responses to Stx. While the plasmid levels and injection methodology were extreme, the study indicates that these sequences are potentially taken up into eukaryotic cells, transcribed, and translated, producing active Stx. Stx genes are present on integrated bacteriophage genomes in EHEC, and Stx-encoding phages are released following bacterial lysis in the gastrointestinal tract. We therefore need to consider whether bacteriophage sequences can be expressed in eukaryotic cells, what the wider implications are for our understanding of many “bacterial” diseases, and the possibility of developing novel interventions that target bacteriophages.A. LengelingA. MahajanD. L. GallyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 6 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 A. Lengeling A. Mahajan D. L. Gally Bacteriophages as Pathogens and Immune Modulators?
description	ABSTRACT While Shiga toxins (Stx) are key determinants of enterohemorrhagic Escherichia coli (EHEC) pathophysiology in humans, their dissemination to target organs following gastrointestinal EHEC infection is still poorly understood. Most types of Stx target cells with globotriaosylceramide (Gb3) receptors, which are expressed on endothelial cells. According to current theory, Stx is trafficked on the surface of peripheral blood cells, and transfer of toxin from these trafficking cells to endothelial cells results in microvascular damage to target organs, including the kidneys and brain. Inside the cell, Stx inhibits protein synthesis, resulting in cell death. Host “repair” responses can lead to microthrombus formation, erythrocyte damage, and reduced oxygen supply, potentially resulting in organ failure. A recent study [L. V. Bentancor et al., mBio 4(5):e00501-13, 2013, doi:10.1128/mBio.00501-13] indicates that another mechanism for Stx “dissemination” needs to be considered. Bentancor et al. demonstrated that high-pressure injection of a plasmid encoding the “prokaryotic” Stx2 sequence into mice can lead to mortality, with pathology indicative of Stx activity and antibody responses to Stx. While the plasmid levels and injection methodology were extreme, the study indicates that these sequences are potentially taken up into eukaryotic cells, transcribed, and translated, producing active Stx. Stx genes are present on integrated bacteriophage genomes in EHEC, and Stx-encoding phages are released following bacterial lysis in the gastrointestinal tract. We therefore need to consider whether bacteriophage sequences can be expressed in eukaryotic cells, what the wider implications are for our understanding of many “bacterial” diseases, and the possibility of developing novel interventions that target bacteriophages.
format	article
author	A. Lengeling A. Mahajan D. L. Gally
author_facet	A. Lengeling A. Mahajan D. L. Gally
author_sort	A. Lengeling
title	Bacteriophages as Pathogens and Immune Modulators?
title_short	Bacteriophages as Pathogens and Immune Modulators?
title_full	Bacteriophages as Pathogens and Immune Modulators?
title_fullStr	Bacteriophages as Pathogens and Immune Modulators?
title_full_unstemmed	Bacteriophages as Pathogens and Immune Modulators?
title_sort	bacteriophages as pathogens and immune modulators?
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/5e803fd52abb47aaa8c08be7aa7ee07d
work_keys_str_mv	AT alengeling bacteriophagesaspathogensandimmunemodulators AT amahajan bacteriophagesaspathogensandimmunemodulators AT dlgally bacteriophagesaspathogensandimmunemodulators
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Bacteriophages as Pathogens and Immune Modulators?

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