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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...

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Autores principales: Clark, Stacie A, Thibault, Derek, Shull, Lauren M, Davis, Kimberly M, Aunins, Emily, van Opijnen, Tim, Isberg, Ralph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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