Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers

ABSTRACT Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to...

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Autores principales:	Sophie Nguyen, Kristi Baker, Benjamin S. Padman, Ruzeen Patwa, Rhys A. Dunstan, Thomas A. Weston, Kyle Schlosser, Barbara Bailey, Trevor Lithgow, Michael Lazarou, Antoni Luque, Forest Rohwer, Richard S. Blumberg, Jeremy J. Barr
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	bacteriophages endocytosis phage-eukaryotic interaction symbiosis transcytosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/65339f7f744a4fe48aedd452b60951cc
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spelling	oai:doaj.org-article:65339f7f744a4fe48aedd452b60951cc2021-11-15T15:51:56ZBacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers10.1128/mBio.01874-172150-7511https://doaj.org/article/65339f7f744a4fe48aedd452b60951cc2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01874-17https://doaj.org/toc/2150-7511ABSTRACT Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used in vitro studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body. IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria. They cannot infect eukaryotic cells but can penetrate epithelial cell layers and spread throughout sterile regions of our bodies, including the blood, lymph, organs, and even the brain. Yet how phages cross these eukaryotic cell layers and gain access to the body remains unknown. In this work, epithelial cells were observed to take up and transport phages across the cell, releasing active phages on the opposite cell surface. Based on these results, we posit that the human body is continually absorbing phages from the gut and transporting them throughout the cell structure and subsequently the body. These results reveal that phages interact directly with the cells and organs of our bodies, likely contributing to human health and immunity.Sophie NguyenKristi BakerBenjamin S. PadmanRuzeen PatwaRhys A. DunstanThomas A. WestonKyle SchlosserBarbara BaileyTrevor LithgowMichael LazarouAntoni LuqueForest RohwerRichard S. BlumbergJeremy J. BarrAmerican Society for Microbiologyarticlebacteriophagesendocytosisphage-eukaryotic interactionsymbiosistranscytosisMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacteriophages endocytosis phage-eukaryotic interaction symbiosis transcytosis Microbiology QR1-502
spellingShingle	bacteriophages endocytosis phage-eukaryotic interaction symbiosis transcytosis Microbiology QR1-502 Sophie Nguyen Kristi Baker Benjamin S. Padman Ruzeen Patwa Rhys A. Dunstan Thomas A. Weston Kyle Schlosser Barbara Bailey Trevor Lithgow Michael Lazarou Antoni Luque Forest Rohwer Richard S. Blumberg Jeremy J. Barr Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
description	ABSTRACT Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used in vitro studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body. IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria. They cannot infect eukaryotic cells but can penetrate epithelial cell layers and spread throughout sterile regions of our bodies, including the blood, lymph, organs, and even the brain. Yet how phages cross these eukaryotic cell layers and gain access to the body remains unknown. In this work, epithelial cells were observed to take up and transport phages across the cell, releasing active phages on the opposite cell surface. Based on these results, we posit that the human body is continually absorbing phages from the gut and transporting them throughout the cell structure and subsequently the body. These results reveal that phages interact directly with the cells and organs of our bodies, likely contributing to human health and immunity.
format	article
author	Sophie Nguyen Kristi Baker Benjamin S. Padman Ruzeen Patwa Rhys A. Dunstan Thomas A. Weston Kyle Schlosser Barbara Bailey Trevor Lithgow Michael Lazarou Antoni Luque Forest Rohwer Richard S. Blumberg Jeremy J. Barr
author_facet	Sophie Nguyen Kristi Baker Benjamin S. Padman Ruzeen Patwa Rhys A. Dunstan Thomas A. Weston Kyle Schlosser Barbara Bailey Trevor Lithgow Michael Lazarou Antoni Luque Forest Rohwer Richard S. Blumberg Jeremy J. Barr
author_sort	Sophie Nguyen
title	Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
title_short	Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
title_full	Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
title_fullStr	Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
title_full_unstemmed	Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
title_sort	bacteriophage transcytosis provides a mechanism to cross epithelial cell layers
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/65339f7f744a4fe48aedd452b60951cc
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Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers

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