Effects of antibiotics on quorum sensing in pseudomonas aeruginosa

Mette Elena Skindersø, Morten Alhede, Richard Kerry Phipps, Liang Yang, Peter O. Jensen, Thomas Bjarnsholt, Thomas B. Rasmussen, Tim Tolker-Nielsen, Niels Høiby, Michael Christian Givskov

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-L-homoserine lactone.
    Original languageEnglish
    JournalAntimicrobial Agents and Chemotherapy
    Volume52
    Issue number10
    Pages (from-to)3648-3663
    ISSN0066-4804
    DOIs
    Publication statusPublished - 2008

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