Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens

Abstract Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial‐killing effects is one of the strategies to combat antibiot...

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Main Authors: Yu Zhang, Pramod Bhasme, Dinesh S. Reddy, Dejian Liu, Zhaoxiao Yu, Tianhu Zhao, Yaqian Zheng, Amit Kumar, Haiying Yu, Luyan Z. Ma
Format: Article
Language:English
Published: Wiley 2023-09-01
Series:mLife
Subjects:
Online Access:https://doi.org/10.1002/mlf2.12087
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author Yu Zhang
Pramod Bhasme
Dinesh S. Reddy
Dejian Liu
Zhaoxiao Yu
Tianhu Zhao
Yaqian Zheng
Amit Kumar
Haiying Yu
Luyan Z. Ma
author_facet Yu Zhang
Pramod Bhasme
Dinesh S. Reddy
Dejian Liu
Zhaoxiao Yu
Tianhu Zhao
Yaqian Zheng
Amit Kumar
Haiying Yu
Luyan Z. Ma
author_sort Yu Zhang
collection DOAJ
description Abstract Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial‐killing effects is one of the strategies to combat antibiotic tolerance. In this study, we discovered a coumarin–chalcone conjugate C9, which can inhibit the biofilm formation of three common pathogens that cause nosocomial infections, namely, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, with the best antibiofilm activity against P. aeruginosa. Further investigations indicate that C9 decreases the synthesis of the key biofilm matrix exopolysaccharide Psl and bacterial second messenger cyclic‐di‐GMP. Meanwhile, C9 can interfere with the regulation of the quorum sensing (QS) system to reduce the virulence of P. aeruginosa. C9 treatment enhances the sensitivity of biofilm to several antibiotics and reduces the survival rate of P. aeruginosa under starvation or oxidative stress conditions, indicating its excellent potential for use as an antibiofilm‐forming and anti‐QS drug.
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spelling doaj.art-2dd84a9cf003493eb4e73a2b7d8cc36c2023-09-28T10:25:52ZengWileymLife2770-100X2023-09-012328329410.1002/mlf2.12087Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogensYu Zhang0Pramod Bhasme1Dinesh S. Reddy2Dejian Liu3Zhaoxiao Yu4Tianhu Zhao5Yaqian Zheng6Amit Kumar7Haiying Yu8Luyan Z. Ma9State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaCentre for Nano and Material Sciences Jain University Bangalore Karnataka IndiaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaCentre for Nano and Material Sciences Jain University Bangalore Karnataka IndiaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing ChinaAbstract Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial‐killing effects is one of the strategies to combat antibiotic tolerance. In this study, we discovered a coumarin–chalcone conjugate C9, which can inhibit the biofilm formation of three common pathogens that cause nosocomial infections, namely, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, with the best antibiofilm activity against P. aeruginosa. Further investigations indicate that C9 decreases the synthesis of the key biofilm matrix exopolysaccharide Psl and bacterial second messenger cyclic‐di‐GMP. Meanwhile, C9 can interfere with the regulation of the quorum sensing (QS) system to reduce the virulence of P. aeruginosa. C9 treatment enhances the sensitivity of biofilm to several antibiotics and reduces the survival rate of P. aeruginosa under starvation or oxidative stress conditions, indicating its excellent potential for use as an antibiofilm‐forming and anti‐QS drug.https://doi.org/10.1002/mlf2.12087biofilmcyclic‐di‐GMPexopolysaccharide PslPseudomonas aeruginosaquorum sensing
spellingShingle Yu Zhang
Pramod Bhasme
Dinesh S. Reddy
Dejian Liu
Zhaoxiao Yu
Tianhu Zhao
Yaqian Zheng
Amit Kumar
Haiying Yu
Luyan Z. Ma
Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
mLife
biofilm
cyclic‐di‐GMP
exopolysaccharide Psl
Pseudomonas aeruginosa
quorum sensing
title Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
title_full Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
title_fullStr Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
title_full_unstemmed Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
title_short Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens
title_sort dual functions a coumarin chalcone conjugate inhibits cyclic di gmp and quorum sensing signaling to reduce biofilm formation and virulence of pathogens
topic biofilm
cyclic‐di‐GMP
exopolysaccharide Psl
Pseudomonas aeruginosa
quorum sensing
url https://doi.org/10.1002/mlf2.12087
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