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Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa
Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1,...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387266/ https://www.ncbi.nlm.nih.gov/pubmed/35913171 http://dx.doi.org/10.1128/iai.00061-22 |
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author | Yam, Joey Kuok Hoong Aung, Thet Tun Chua, Song Lin Cheng, Yingying Kohli, Gurjeet Singh Zhou, Jianuan Constancias, Florentin Liu, Yang Cai, Zhao Salido, May Margarette Santillan Drautz-Moses, Daniela I. Rice, Scott A. Schuster, Stephan Christoph Boo, Zhao Zhi Wu, Bin Kjelleberg, Staffan Tolker-Nielsen, Tim Lakshminarayanan, Rajamani Beuerman, Roger W. Yang, Liang Givskov, Michael |
author_facet | Yam, Joey Kuok Hoong Aung, Thet Tun Chua, Song Lin Cheng, Yingying Kohli, Gurjeet Singh Zhou, Jianuan Constancias, Florentin Liu, Yang Cai, Zhao Salido, May Margarette Santillan Drautz-Moses, Daniela I. Rice, Scott A. Schuster, Stephan Christoph Boo, Zhao Zhi Wu, Bin Kjelleberg, Staffan Tolker-Nielsen, Tim Lakshminarayanan, Rajamani Beuerman, Roger W. Yang, Liang Givskov, Michael |
author_sort | Yam, Joey Kuok Hoong |
collection | PubMed |
description | Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a p(lac)-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo p(lac)-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the p(lac)-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea. |
format | Online Article Text |
id | pubmed-9387266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-93872662022-08-19 Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa Yam, Joey Kuok Hoong Aung, Thet Tun Chua, Song Lin Cheng, Yingying Kohli, Gurjeet Singh Zhou, Jianuan Constancias, Florentin Liu, Yang Cai, Zhao Salido, May Margarette Santillan Drautz-Moses, Daniela I. Rice, Scott A. Schuster, Stephan Christoph Boo, Zhao Zhi Wu, Bin Kjelleberg, Staffan Tolker-Nielsen, Tim Lakshminarayanan, Rajamani Beuerman, Roger W. Yang, Liang Givskov, Michael Infect Immun Host Response and Inflammation Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a p(lac)-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo p(lac)-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the p(lac)-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea. American Society for Microbiology 2022-08-01 /pmc/articles/PMC9387266/ /pubmed/35913171 http://dx.doi.org/10.1128/iai.00061-22 Text en Copyright © 2022 Yam et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Host Response and Inflammation Yam, Joey Kuok Hoong Aung, Thet Tun Chua, Song Lin Cheng, Yingying Kohli, Gurjeet Singh Zhou, Jianuan Constancias, Florentin Liu, Yang Cai, Zhao Salido, May Margarette Santillan Drautz-Moses, Daniela I. Rice, Scott A. Schuster, Stephan Christoph Boo, Zhao Zhi Wu, Bin Kjelleberg, Staffan Tolker-Nielsen, Tim Lakshminarayanan, Rajamani Beuerman, Roger W. Yang, Liang Givskov, Michael Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title | Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title_full | Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title_fullStr | Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title_full_unstemmed | Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title_short | Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa |
title_sort | elevated c-di-gmp levels and expression of the type iii secretion system promote corneal infection by pseudomonas aeruginosa |
topic | Host Response and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387266/ https://www.ncbi.nlm.nih.gov/pubmed/35913171 http://dx.doi.org/10.1128/iai.00061-22 |
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