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Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites
Within deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316508/ https://www.ncbi.nlm.nih.gov/pubmed/32543373 http://dx.doi.org/10.7554/eLife.58106 |
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author | Clark, Stacie A Thibault, Derek Shull, Lauren M Davis, Kimberly M Aunins, Emily van Opijnen, Tim Isberg, Ralph |
author_facet | Clark, Stacie A Thibault, Derek Shull, Lauren M Davis, Kimberly M Aunins, Emily van Opijnen, Tim Isberg, Ralph |
author_sort | Clark, Stacie A |
collection | PubMed |
description | Within deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicrobial factors. To overcome the limited ability to manipulate these infection sites, we established a system for Yersinia pseudotuberculosis (Yptb) growth in microfluidics-driven microdroplets that regenerates microbial social behavior in tissues. Chemical generation of nitric oxide (NO) in the absence of immune cells was sufficient to reconstruct microbial social behavior, as witnessed by expression of the NO-inactivating protein Hmp on the extreme periphery of microcolonies, mimicking spatial regulation in tissues. Similarly, activated macrophages that expressed inducible NO synthase (iNOS) drove peripheral expression of Hmp, allowing regeneration of social behavior observed in tissues. These results argue that topologically correct microbial tissue growth and associated social behavior can be reconstructed in culture. |
format | Online Article Text |
id | pubmed-7316508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73165082020-06-29 Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites Clark, Stacie A Thibault, Derek Shull, Lauren M Davis, Kimberly M Aunins, Emily van Opijnen, Tim Isberg, Ralph eLife Immunology and Inflammation Within deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicrobial factors. To overcome the limited ability to manipulate these infection sites, we established a system for Yersinia pseudotuberculosis (Yptb) growth in microfluidics-driven microdroplets that regenerates microbial social behavior in tissues. Chemical generation of nitric oxide (NO) in the absence of immune cells was sufficient to reconstruct microbial social behavior, as witnessed by expression of the NO-inactivating protein Hmp on the extreme periphery of microcolonies, mimicking spatial regulation in tissues. Similarly, activated macrophages that expressed inducible NO synthase (iNOS) drove peripheral expression of Hmp, allowing regeneration of social behavior observed in tissues. These results argue that topologically correct microbial tissue growth and associated social behavior can be reconstructed in culture. eLife Sciences Publications, Ltd 2020-06-16 /pmc/articles/PMC7316508/ /pubmed/32543373 http://dx.doi.org/10.7554/eLife.58106 Text en © 2020, Clark et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Clark, Stacie A Thibault, Derek Shull, Lauren M Davis, Kimberly M Aunins, Emily van Opijnen, Tim Isberg, Ralph Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title | Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title_full | Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title_fullStr | Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title_full_unstemmed | Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title_short | Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites |
title_sort | topologically correct synthetic reconstruction of pathogen social behavior found during yersinia growth in deep tissue sites |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316508/ https://www.ncbi.nlm.nih.gov/pubmed/32543373 http://dx.doi.org/10.7554/eLife.58106 |
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