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,...
Saved in:
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2022
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/163875 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-163875 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-1638752022-12-24T23:31:45Z 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 Drautz-Moses, Daniela Isabel 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 School of Biological Sciences Singapore Centre for Environmental Life Sciences and Engineering Science::Medicine Pseudomonas Aeruginosa Transcriptomics 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 plac-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 plac-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 plac-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. Ministry of Education (MOE) National Research Foundation (NRF) Published version This research was supported by the National Research Foundation and Ministry of Education Singapore under its Research Centre of Excellence Program and AcRF Tier 2 (MOE2016-T2-1-010) from the Ministry of Education, Singapore. 2022-12-21T01:57:45Z 2022-12-21T01:57:45Z 2022 Journal Article Yam, J. K. H., Aung, T. T., Chua, S. L., Cheng, Y., Kohli, G. S., Zhou, J., Constancias, F., Liu, Y., Cai, Z., Salido, M. M., Drautz-Moses, D. I., Rice, S. A., Schuster, S. C., Boo, Z. Z., Wu, B., Kjelleberg, S., Tolker-Nielsen, T., Lakshminarayanan, R., Beuerman, R. W., ...Givskov, M. (2022). Elevated c-di-GMP levels and expression of the type III secretion system promote corneal infection by Pseudomonas aeruginosa. Infection and Immunity, 90(8), e0006122-. https://dx.doi.org/10.1128/iai.00061-22 0019-9567 https://hdl.handle.net/10356/163875 10.1128/iai.00061-22 35913171 2-s2.0-85136910897 8 90 e0006122 en MOE2016-T2-1-010 Infection and Immunity © 2022 Yam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. application/pdf |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Science::Medicine Pseudomonas Aeruginosa Transcriptomics |
spellingShingle |
Science::Medicine Pseudomonas Aeruginosa Transcriptomics 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 Drautz-Moses, Daniela Isabel 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 |
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 plac-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 plac-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 plac-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. |
author2 |
School of Biological Sciences |
author_facet |
School of Biological Sciences 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 Drautz-Moses, Daniela Isabel 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 |
format |
Article |
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 Drautz-Moses, Daniela Isabel 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 |
title |
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_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_sort |
elevated c-di-gmp levels and expression of the type iii secretion system promote corneal infection by pseudomonas aeruginosa |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/163875 |
_version_ |
1753801128664891392 |