scholarly journals Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Sophie Nguyen ◽  
Kristi Baker ◽  
Benjamin S. Padman ◽  
Ruzeen Patwa ◽  
Rhys A. Dunstan ◽  
...  

ABSTRACTBacterial 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 usedin vitrostudies 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.IMPORTANCEBacteriophages (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.

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Preethi Balasubramanian ◽  
Leonie A. Strobel ◽  
Ulrich Kneser ◽  
Aldo R. Boccaccini

AbstractZinc is a vital and beneficial trace element found in the human body. Though found in small proportions, zinc performs a variety of functions in relation to the immune system, cell division, fertility and the body growth and maintenance. In particular, zinc is proven to be a necessary element for the formation, mineralization, development and maintenance of healthy bones. Considering this attractive attributes of zinc, recent research has widely focused on using zinc along with silicate-based bioactive glasses for bone tissue engineering applications. This paper reviews relevant literature discussing the significance of zinc in the human body, along with its ability to enhance antibacterial effects, bioactivity and distinct physical, structural and mechanical properties of bioactive glasses. In this context, even if the present analysis is not meant to be exhaustive and only representative studies are discussed, literature results confirm that it is essential to understand the properties of zinc-containing bioactive glasses with respect to their in vitro biological behavior, possible cytotoxic effects and degradation characteristics to be able to effectively apply these glasses in bone regeneration strategies. Topics attracting increasing research efforts in this field are elaborated in detail in this review, including a summary of the structural, physical, biological and mechanical properties of zinc-containing bioactive glasses. This paper also presents an overview of the various applications in which zinc-containing bioactive glasses are considered for use as bone tissue scaffolds, bone filling granules, bioactive coatings and bone cements, and advances and remaining challenges are highlighted.


2020 ◽  
Author(s):  
Marion C. Bichet ◽  
Wai Hoe Chin ◽  
William Richards ◽  
Yu-Wei Lin ◽  
Laura Avellaneda-Franco ◽  
...  

AbstractFor over 100 years, bacteriophages have been known as viruses that infect bacteria. Yet it is becoming increasingly apparent that bacteriophages, or phages for short, have tropisms outside their bacterial hosts. During phage therapy, high doses of phages are directly administered and disseminated throughout the body, facilitating broad interactions with eukaryotic cells. Using live cell imaging across a range of cell lines we demonstrate that cell type plays a major role in phage internalisation and that smaller phages (< 100 nm) are internalised at higher rates. Uptake rates were validated under physiological shear stress conditions using a microfluidic device that mimics the shear stress to which endothelial cells are exposed to in the human body. Phages were found to rapidly adhere to eukaryotic cell layers, with adherent phages being subsequently internalised by macropinocytosis and functional phages accumulating and stably persisting intracellularly. Finally, we incorporate these results into an established pharmacokinetic model demonstrating the potential impact of phage accumulation by these cell layers, which represents a major sink for circulating phages in the body. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.


1859 ◽  
Vol 149 ◽  
pp. 469-477

During the last few years anatomists have considered the muscular substance of the bladder to be composed of elongated contractile fibre-cells, each with a nucleus in it, which possess free ends, and overlap at their pointed extremities without being united or joined together. This notion of the cell-structure originated with Professor Kölliker; and it has since received very general acceptance. From the correctness of that opinion I am led to dissent by my researches; and I purpose to show in this communication to the Royal Society, that both the involuntary muscular tissue of the bladder and the voluntary muscular substance in other parts of the human body have a like composition. In a former paper to the Society (in June 1856) I made the announcement that the views now bought forward of the muscular structure of the bladder were applicable to the involuntary muscular tissue in general; but as my declaration was received with doubt, I determine to withhold its publication until I had been able to repeat my microscopical observations. Before this time I hoped to have completed the task imposed on myself, but occupation has left me leisure enough to examine thoroughly only the muscular structure of the urinary bladder. As my idea is confirmed by the result of the second examination of that viscus, I submit this paper with greater confidence to the consideration researches into the nature of the involuntary muscular tissue in other parts of the body.


2019 ◽  
Vol 14 (11) ◽  
pp. 745-760 ◽  
Author(s):  
Maciej Żaczek ◽  
Andrzej Górski ◽  
Aneta Skaradzińska ◽  
Marzanna Łusiak-Szelachowska ◽  
Beata Weber-Dąbrowska

The inability to infect eukaryotic cells has been considered as the most undeniable feature of all bacterial viruses. Such specificity, limited only for bacterial hosts, raises questions about the paths and challenges phages should overcome when circulating through the human body. Recently, it has been shown that phages are able to continually penetrate human organs and tissues. Latest reports revealed that phages can cross eukaryotic cell barriers both para- and transcellularly and even reach the nucleus. Further, phages are capable of internalizing within cells through different endocytic mechanisms. Such phenomenon indicates that phages could shape human microbiome composition and affect all aspects of human health. Thus, herein, we summarize the current state of knowledge and describe this phenomenon with a particular emphasis on endocytic pathways.


2009 ◽  
Vol 136 (2) ◽  
pp. 110-116 ◽  
Author(s):  
L. Belhadj Salem ◽  
C. Bosquillon ◽  
L.A. Dailey ◽  
L. Delattre ◽  
G.P. Martin ◽  
...  

2021 ◽  
Vol 2 (3) ◽  
pp. 100697
Author(s):  
Marion C. Bichet ◽  
Ruzeen Patwa ◽  
Jeremy J. Barr
Keyword(s):  

2014 ◽  
Vol 36 (3) ◽  
pp. 8-12
Author(s):  
Martin C. Garnett ◽  
Driton Vllasaliu ◽  
Snow Stolnik ◽  
Franco H. Falcone

The development of medicines during the 20th Century was initially based on oral delivery of drugs via the gastrointestinal tract. To enhance understanding of rate of uptake of different drugs and formulations and reduce the need for animal testing, in vitro models based on gut epithelial cell models were developed in the 1980s and 1990s. With the advent of biotechnology, an increasing number of drugs based on proteins and other biomolecules are being produced, which currently require parenteral administration (by injection). To avoid the need for injection, alternative routes of delivery are being sought for these molecules, including mucosal routes of the gastrointestinal tract and the lung. In parallel with this, the field of ‘nanotechnology’ began to develop. Nanotechnology offers both solutions and problems. ‘Nanomedicines’ over a range of nano sizes appear to offer some solutions for delivery, provided that they could cross epithelial barriers. In contrast, there remains considerable concern that the many different types of nanoparticles in development for electronics and new materials may be taken up into the body and cause harm. There are therefore clear needs for epithelial models which allow us to not only screen conventional drugs for absorption, but also assess potential non-invasive delivery of biologics and nanomedicines, as well as screen easily and reliably for nanotoxicology1. As it is the same barrier involved in all of these cases, we need a single epithelial model that can adequately reflect and give accurate answers for all of these different barrier problems. In this article, we assess the properties needed for an epithelial cellular model, the current state of the art, and some recent work developing a more accurate and comprehensive model.


2019 ◽  
Vol 70 (4) ◽  
pp. 1144-1148
Author(s):  
Nicoleta Simionescu ◽  
Anca Ravoiu ◽  
Lidia Benea

316L Stainless steels are widely used in biomedical applications with respect to their excellent corrosion resistance, nonmagnetic properties, high ductility and acceptable biocompatibility. There have been made electrochemical studies in-vitro in order to determine the corrosion reactions, which are necessary for foreseeing the behavior of the materials used in orthodontic applications. The degradation of metals and alloys in the human body is a combination of effects due to corrosion and mechanical activities. In dentistry, 316L stainless steel are used in a variety of applications: sterilized instruments, endodontic files in root canal therapy, metal posts in root canal treated teeth, temporary crowns, arch wires and brackets in orthodontics, a necessary condition for these applications must to resist to pitting corrosion. The pitting corrosion can be observed only in the case of passivable steels and in the presence of halogen or sulphur ions, in saline or acidic media like the human body. this type of corrosion propagates under the form of small pits, which give off to a significant quantity of metal ions, being very dangerous to the body. The metal ions resulted from the corrosive processes have allergic, carcinogenic and cytotoxic effects. The aim of this work was to evaluate the corrosion behavior of 316L stainless steel immersed in two artificial saliva solutions. The electrochemical measurements such as: open Circuit Potential (OCP), linear Polarization Resistance (LRP), and electrochemical Impedance Spectroscopy (EIS), methods were used to fulfill the corrosion evaluation. The research work concludes that the increase of the pH with a higher concentration of chloride contents lead to a lowest corrosion resistance while a decrease of the pH with a lowest concentration of chlorides contents reveals a higher corrosion resistance.


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