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

Yam, JKH; Aung, TT; Chua, SL; Cheng, Y; Kohli, GS; Zhou, J; Constancias, F; Liu, Y; Cai, Z; Salido, MMS; Drautz-Moses, DI; Rice, SA; Schuster, SC; Boo, ZZ; Wu, B; Kjelleberg, S; Tolker-Nielsen, T; Lakshminarayanan, R; Beuerman, RW; Yang, L; Givskov, M

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

Yam, JKH Aung, TT Chua, SL Cheng, Y Kohli, GS Zhou, J Constancias, F Liu, Y Cai, Z Salido, MMS Drautz-Moses, DI Rice, SA Schuster, SC Boo, ZZ Wu, B Kjelleberg, S Tolker-Nielsen, T Lakshminarayanan, R Beuerman, RW Yang, L Givskov, M

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Publisher:: American Society for Microbiology
Publication Type:: Journal Article
Citation:: Infection and Immunity, 2022, 90, (8), pp. 1-17
Issue Date:: 2022-08-18

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Field	Value	Language
dc.contributor.author	Yam, JKH
dc.contributor.author	Aung, TT
dc.contributor.author	Chua, SL
dc.contributor.author	Cheng, Y
dc.contributor.author	Kohli, GS
dc.contributor.author	Zhou, J
dc.contributor.author	Constancias, F
dc.contributor.author	Liu, Y
dc.contributor.author	Cai, Z
dc.contributor.author	Salido, MMS
dc.contributor.author	Drautz-Moses, DI
dc.contributor.author	Rice, SA
dc.contributor.author	Schuster, SC
dc.contributor.author	Boo, ZZ
dc.contributor.author	Wu, B
dc.contributor.author	Kjelleberg, S
dc.contributor.author	Tolker-Nielsen, T
dc.contributor.author	Lakshminarayanan, R
dc.contributor.author	Beuerman, RW
dc.contributor.author	Yang, L
dc.contributor.author	Givskov, M
dc.date.accessioned	2022-12-05T04:22:22Z
dc.date.available	2022-12-05T04:22:22Z
dc.date.issued	2022-08-18
dc.identifier.citation	Infection and Immunity, 2022, 90, (8), pp. 1-17
dc.identifier.issn	0019-9567
dc.identifier.issn	1098-5522
dc.identifier.uri	http://hdl.handle.net/10453/164130
dc.description.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 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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	American Society for Microbiology
dc.relation.ispartof	Infection and Immunity
dc.relation.isbasedon	10.1128/iai.00061-22
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences
dc.subject.classification	Microbiology
dc.subject.mesh	Animals
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Biofilms
dc.subject.mesh	Cyclic GMP
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Mice
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Type III Secretion Systems
dc.subject.mesh	Animals
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Biofilms
dc.subject.mesh	Cyclic GMP
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Mice
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Type III Secretion Systems
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Biofilms
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Cyclic GMP
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Type III Secretion Systems
dc.title	Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa.
dc.type	Journal Article
utslib.citation.volume	90
utslib.location.activity	United States
utslib.for	06 Biological Sciences
utslib.for	07 Agricultural and Veterinary Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - AIMI - Australian Institute for Microbiology & Infection
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-05T04:21:18Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	90
utslib.citation.issue	8

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 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.

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http://hdl.handle.net/10453/164130