Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels
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Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels. / Chua, Song Lin; Ding, Yichen; Liu, Yang; Cai, Zhao; Zhou, Jianuan; Swarup, Sanjay; Drautz-Moses, Daniela I.; Schuster, Stephan Christoph; Kjelleberg, Staffan; Givskov, Michael; Yang, Liang.
In: Open Biology, Vol. 6, 160162, 11.2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels
AU - Chua, Song Lin
AU - Ding, Yichen
AU - Liu, Yang
AU - Cai, Zhao
AU - Zhou, Jianuan
AU - Swarup, Sanjay
AU - Drautz-Moses, Daniela I.
AU - Schuster, Stephan Christoph
AU - Kjelleberg, Staffan
AU - Givskov, Michael
AU - Yang, Liang
PY - 2016/11
Y1 - 2016/11
N2 - 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.
AB - 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.
KW - biofilms
KW - c-di-GMP
KW - rough small colony variants
KW - reactive oxygen species
KW - Pseudomonas aeruginosa
KW - adaptive evolution
UR - https://royalsocietypublishing.org/doi/10.1098/rsob.170197
U2 - 10.1098/rsob.160162
DO - 10.1098/rsob.160162
M3 - Journal article
C2 - 27881736
VL - 6
JO - Open Biology
JF - Open Biology
SN - 2046-2441
M1 - 160162
ER -
ID: 171661172