The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms

Wen-Chi Chiang, Sünje Johanna Pamp, Martin Nilsson, Michael Christian Givskov, Tim Tolker-Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Biofilms are reported to be inherently refractory toward antimicrobial attack and, therefore, cause problems in industrial and medical settings. Pseudomonas aeruginosa biofilms contain subpopulations that exhibit high metabolic activity and subpopulations that exhibit low metabolic activity. We have found that membrane-targeting antimicrobials such as colistin, EDTA, SDS, and chlorhexidine specifically kill the inactive subpopulation in P. aeruginosa biofilms, whereas the active subpopulation survives exposure to these compounds. Because treatment of P. aeruginosa biofilms with the membrane-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes encoding lipopolysaccharide modification enzymes, as well as on the mexAB-oprM, mexCD-oprJ, and muxABC-opmB genes encoding antimicrobial efflux pumps, but does not depend on the mexPQ-opmE efflux pump genes. Development of chlorhexidine-tolerant subpopulations was found to depend on the mexCD-oprJ genes, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes. Our data suggest that the active subpopulation in P. aeruginosa biofilms is able to adapt to exposure to membrane-targeting agents through the use of different genetic determinants, dependent on the specific membrane-targeting compound.
    Original languageEnglish
    JournalF E M S Immunology and Medical Microbiology
    Volume65
    Issue number2, Sp. Iss. SI
    Pages (from-to)245-256
    ISSN0928-8244
    DOIs
    Publication statusPublished - 2012

    Keywords

    • Gram-Negative Aerobic Rods and Cocci Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Pseudomonadaceae [06508] Pseudomonas aeruginosa species
    • Pseudomonas aeruginosa mexAB gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa mexAB-oprM gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa mexCD gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa mexCD-oprJ gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa mexPQ gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa mexPQ-opmE gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa muxABC gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa muxABC-opmB gene [Pseudomonadaceae] expression
    • Pseudomonas aeruginosa pmr gene [Pseudomonadaceae] expression
    • chlorhexidine 55-56-1 antibacterial-drug, antiinfective-drug
    • colistin 1066-17-7 antibacterial-drug, antiinfective-drug
    • EDTA 60-00-4 antibacterial-drug, antiinfective-drug
    • lipopolysaccharide modification enzyme
    • SDS antibacterial-drug, antiinfective-drug
    • 03502, Genetics - General
    • 10060, Biochemistry studies - General
    • 10064, Biochemistry studies - Proteins, peptides and amino acids
    • 12512, Pathology - Therapy
    • 22002, Pharmacology - General
    • 31000, Physiology and biochemistry of bacteria
    • 31500, Genetics of bacteria and viruses
    • 38502, Chemotherapy - General, methods and metabolism
    • 38504, Chemotherapy - Antibacterial agents
    • Infection
    • Molecular Genetics
    • Pharmacology
    • Pseudomonas aeruginosa biofilm infection bacterial disease drug therapy, etiology
    • antimicrobial tolerance
    • molecular mechanism
    • Biochemistry and Molecular Biophysics
    • combination therapy therapeutic and prophylactic techniques, clinical techniques

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