rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure

Abstract Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Resu...

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Main Authors: Xiangke Duan, Yanrong Pan, Zhao Cai, Yumei Liu, Yingdan Zhang, Moxiao Liu, Yang Liu, Ke Wang, Lianhui Zhang, Liang Yang
Format: Article
Language:English
Published: BMC 2021-07-01
Series:Cell & Bioscience
Subjects:
Online Access:https://doi.org/10.1186/s13578-021-00655-9
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author Xiangke Duan
Yanrong Pan
Zhao Cai
Yumei Liu
Yingdan Zhang
Moxiao Liu
Yang Liu
Ke Wang
Lianhui Zhang
Liang Yang
author_facet Xiangke Duan
Yanrong Pan
Zhao Cai
Yumei Liu
Yingdan Zhang
Moxiao Liu
Yang Liu
Ke Wang
Lianhui Zhang
Liang Yang
author_sort Xiangke Duan
collection DOAJ
description Abstract Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Results In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants. Conclusion Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.
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spelling doaj.art-cc4d254c71f34c8e9b69e242a3710ed42022-12-21T18:21:10ZengBMCCell & Bioscience2045-37012021-07-0111111310.1186/s13578-021-00655-9rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressureXiangke Duan0Yanrong Pan1Zhao Cai2Yumei Liu3Yingdan Zhang4Moxiao Liu5Yang Liu6Ke Wang7Lianhui Zhang8Liang Yang9Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Center, South China Agricultural UniversitySchool of Medicine, Southern University of Science and TechnologySchool of Medicine, Southern University of Science and TechnologySchool of Medicine, Southern University of Science and TechnologySchool of Medicine, Southern University of Science and TechnologySchool of Medicine, Southern University of Science and TechnologySouthern University of Science and Technology HospitalDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityGuangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Center, South China Agricultural UniversitySchool of Medicine, Southern University of Science and TechnologyAbstract Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Results In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants. Conclusion Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.https://doi.org/10.1186/s13578-021-00655-9Experimental biofilm evolutionPseudomonas aeruginosaSigma factor RpoSBiofilmsCyclic-di-GMPVirulence
spellingShingle Xiangke Duan
Yanrong Pan
Zhao Cai
Yumei Liu
Yingdan Zhang
Moxiao Liu
Yang Liu
Ke Wang
Lianhui Zhang
Liang Yang
rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
Cell & Bioscience
Experimental biofilm evolution
Pseudomonas aeruginosa
Sigma factor RpoS
Biofilms
Cyclic-di-GMP
Virulence
title rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
title_full rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
title_fullStr rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
title_full_unstemmed rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
title_short rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
title_sort rpos mutation variants are selected in pseudomonas aeruginosa biofilms under imipenem pressure
topic Experimental biofilm evolution
Pseudomonas aeruginosa
Sigma factor RpoS
Biofilms
Cyclic-di-GMP
Virulence
url https://doi.org/10.1186/s13578-021-00655-9
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