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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,...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
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.
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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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