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Title: Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels
Authors: Chua, S.L
Ding, Y
Liu, Y
Cai, Z
Zhou, J
Swarup, S 
Drautz-Moses, D.I
Schuster, S.C
Kjelleberg, S
Givskov, M
Yang, L
Keywords: bacterial protein
bis(3',5')-cyclic diguanylic acid
cyclic GMP
hydrogen peroxide
reactive oxygen metabolite
analogs and derivatives
drug effects
gene expression regulation
Pseudomonas aeruginosa
Bacterial Proteins
Biological Evolution
Cyclic GMP
Gene Expression Regulation, Bacterial
Hydrogen Peroxide
Pseudomonas aeruginosa
Reactive Oxygen Species
Issue Date: 2016
Citation: Chua, S.L, Ding, Y, Liu, Y, Cai, Z, Zhou, J, Swarup, S, Drautz-Moses, D.I, Schuster, S.C, Kjelleberg, S, Givskov, M, Yang, L (2016). Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels. Open biology 6 (11). ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The host immune system offers a hostile environment with antimicrobials and reactive oxygen species (ROS) that are detrimental to bacterial pathogens, forcing them to adapt and evolve for survival. However, the contribution of oxidative stress to pathogen evolution remains elusive. Using an experimental evolution strategy, we show that exposure of the opportunistic pathogen Pseudomonas aeruginosa to sub-lethal hydrogen peroxide (H2O2) levels over 120 generations led to the emergence of pro-biofilm rough small colony variants (RSCVs), which could be abrogated by l-glutathione antioxidants. Comparative genomic analysis of the RSCVs revealed that mutations in the wspF gene, which encodes for a repressor of WspR diguanylate cyclase (DGC), were responsible for increased intracellular cyclic-di-GMP content and production of Psl exopolysaccharide. Psl provides the first line of defence against ROS and macrophages, ensuring the survival fitness of RSCVs over wild-type P. aeruginosa Our study demonstrated that ROS is an essential driving force for the selection of pro-biofilm forming pathogenic variants. Understanding the fundamental mechanism of these genotypic and phenotypic adaptations will improve treatment strategies for combating chronic infections. © 2016 The Authors.
Source Title: Open biology
ISSN: 20462441
DOI: 10.1098/rsob.160162
Rights: Attribution 4.0 International
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