Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation , we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment . We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962583PMC
http://dx.doi.org/10.1080/19490976.2024.2331520DOI Listing

Publication Analysis

Top Keywords

phage translocation
20
colonoid monolayer
12
model possessing
8
mucus
8
colonic mucus
8
translocation
7
phage
6
human colonoid-derived
4
monolayer
4
colonoid-derived monolayer
4

Similar Publications

Virus-Receptor Interactions and Receptor-Mediated Virus Entry into Host Cells.

Subcell Biochem

December 2024

Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.

The virus particles described in the previous chapters of this book are vehicles that transmit the viral genome and the infection from cell to cell. To initiate the infective cycle, the viral genome must therefore translocate from the viral particle to the cell cytoplasm. Via distinct proteins or motifs in their outermost shell, the particles of animal viruses or bacteriophages attach initially to specific receptors on the host cell surface.

View Article and Find Full Text PDF

Carbapenemase-producing (KPC) are globally emerging pathogens that cause life-threatening infections. Novel treatment alternatives are urgently needed. We therefore investigated the effectiveness of three novel bacteriophages (Spivey, Pharr, and Soft) in a neutropenic murine model of KPC gastrointestinal colonization, translocation, and disseminated infection.

View Article and Find Full Text PDF

Conformational changes in and translocation of small proteins: insights into the ejection mechanism of podophages.

J Virol

December 2024

Institute of Interdisciplinary Studies, Key Laboratory for Matter Microstructure and Function of Hunan Province, Key Laboratory of Low-dimensional Quantum Structures and Quantum Control, School of Physics and Electronics, Hunan Normal University, Changsha, China.

Unlabelled: Podophage tails are too short to span the cell envelope during infection. Consequently, podophages initially eject the core proteins within the head for the formation of an elongated trans-envelope channel for DNA ejection. Although the core proteins of bacteriophage T7 have been resolved at near-atomic resolution, the mechanisms of core proteins and DNA ejection remain to be fully elucidated.

View Article and Find Full Text PDF

has been involved in transfusion-transmitted fatalities associated with platelet concentrates (PCs) due to its heightened pathogenicity enhanced by genome-encoded virulence and antibiotic resistance genes. This may be facilitated by mobile genetic elements (MGEs) that can cause rearrangements. Several factors contribute to virulence, including the type VII secretion system (T7SS), composed of six core genes conserved across strains.

View Article and Find Full Text PDF

Acute lung injury caused by is attributed to the translocation of cytotoxin into pulmonary epithelial cells via the type III secretion system. This virulence can be blocked with a specific antibody against PcrV in this secretion system. However, because anti-PcrV antibodies do not have bactericidal activity, the treatment of bacteria depends on the phagocytic system of the host.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!