Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa

Author:

Yam Joey Kuok Hoong1,Aung Thet Tun23,Chua Song Lin4,Cheng Yingying5,Kohli Gurjeet Singh6,Zhou Jianuan7,Constancias Florentin8,Liu Yang9,Cai Zhao9,Salido May Margarette Santillan1,Drautz-Moses Daniela I.1,Rice Scott A.11011,Schuster Stephan Christoph110,Boo Zhao Zhi10,Wu Bin10,Kjelleberg Staffan11012,Tolker-Nielsen Tim13ORCID,Lakshminarayanan Rajamani21415,Beuerman Roger W.2161718,Yang Liang9ORCID,Givskov Michael113ORCID

Affiliation:

1. Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore

2. Ocular Infections and Anti-Microbials Research Group, Singapore Eye Research Institute, Singapore, Singapore

3. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore

4. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong

5. Forensics Genomics International (FGI), BGI-Shenzhen, Shenzhen, China

6. Alfred Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Bremerhaven, Germany

7. Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China

8. Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland

9. School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China

10. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

11. CSIRO, Agriculture and Food, Microbiomes for One Systems Health, Canberra, Australia

12. School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, Australia

13. Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

14. Department of Pharmacy, National University of Singapore, Singapore, Singapore

15. Academic Clinical Program in Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore

16. SRP Neuroscience and Behavioural Disorders and Emerging Infectious Diseases, Duke-NUS, Singapore, Singapore

17. Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

18. Department of Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA

Abstract

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 Δ wspF 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.

Funder

National Research Foundation Singapore

Ministry of Education - Singapore

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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