Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria

Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections. I...

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Main Authors: Chiang, Wen-Chi, Wu, H., Nielsen, T. E., Christensen, Louise Dahl, Gennip, Maria van, Rybtke, Morten Theil, Alhede, Morten, Høiby, Niels, Givskov, Michael, Tolker-Nielsen, Tim
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Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/99850
http://hdl.handle.net/10220/17680
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-998502022-02-16T16:28:57Z Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria Chiang, Wen-Chi Wu, H. Nielsen, T. E. Christensen, Louise Dahl Gennip, Maria van Rybtke, Morten Theil Alhede, Morten Høiby, Niels Givskov, Michael Tolker-Nielsen, Tim DRNTU::Science::Biological sciences Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections. It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can be used for biofilm control in vivo. We constructed a Pseudomonas aeruginosa strain in which a reduction in the c-di-GMP level can be achieved via induction of the Escherichia coli YhjH c-di-GMP phosphodiesterase. Initial experiments showed that induction of yhjH expression led to dispersal of the majority of the bacteria in in vitro-grown P. aeruginosa biofilms. Subsequently, we demonstrated that P. aeruginosa biofilms growing on silicone implants, located in the peritoneal cavity of mice, dispersed after induction of the YhjH protein. Bacteria accumulated temporarily in the spleen after induction of biofilm dispersal, but the mice tolerated the dispersed bacteria well. The present work provides proof of the concept that modulation of the c-di-GMP level in bacteria is a viable strategy for biofilm control. 2013-11-15T06:04:13Z 2019-12-06T20:12:20Z 2013-11-15T06:04:13Z 2019-12-06T20:12:20Z 2013 2013 Journal Article Christensen, L. D., Gennip, M. v., Rybtke, M. T., Wu, H., Chiang, W. C., Alhede, M., et al. (2013). Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria. Infection and immunity, 81(8), 2705-2713. 0019-9567 https://hdl.handle.net/10356/99850 http://hdl.handle.net/10220/17680 10.1128/IAI.00332-13 23690403 en Infection and immunity
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Chiang, Wen-Chi
Wu, H.
Nielsen, T. E.
Christensen, Louise Dahl
Gennip, Maria van
Rybtke, Morten Theil
Alhede, Morten
Høiby, Niels
Givskov, Michael
Tolker-Nielsen, Tim
Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
description Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections. It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can be used for biofilm control in vivo. We constructed a Pseudomonas aeruginosa strain in which a reduction in the c-di-GMP level can be achieved via induction of the Escherichia coli YhjH c-di-GMP phosphodiesterase. Initial experiments showed that induction of yhjH expression led to dispersal of the majority of the bacteria in in vitro-grown P. aeruginosa biofilms. Subsequently, we demonstrated that P. aeruginosa biofilms growing on silicone implants, located in the peritoneal cavity of mice, dispersed after induction of the YhjH protein. Bacteria accumulated temporarily in the spleen after induction of biofilm dispersal, but the mice tolerated the dispersed bacteria well. The present work provides proof of the concept that modulation of the c-di-GMP level in bacteria is a viable strategy for biofilm control.
format Article
author Chiang, Wen-Chi
Wu, H.
Nielsen, T. E.
Christensen, Louise Dahl
Gennip, Maria van
Rybtke, Morten Theil
Alhede, Morten
Høiby, Niels
Givskov, Michael
Tolker-Nielsen, Tim
author_facet Chiang, Wen-Chi
Wu, H.
Nielsen, T. E.
Christensen, Louise Dahl
Gennip, Maria van
Rybtke, Morten Theil
Alhede, Morten
Høiby, Niels
Givskov, Michael
Tolker-Nielsen, Tim
author_sort Chiang, Wen-Chi
title Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
title_short Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
title_full Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
title_fullStr Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
title_full_unstemmed Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria
title_sort clearance of pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-gmp level in the bacteria
publishDate 2013
url https://hdl.handle.net/10356/99850
http://hdl.handle.net/10220/17680
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