Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

Research output: Contribution to journalJournal articleResearchpeer-review

Thomas Bjarnsholt, Peter Østrup Jensen, Mette Burmølle, Morten Hentzer, Janus A J Haagensen, Hans Petter Hougen, Henrik Calum, Kit G Madsen, Claus Moser, Søren Molin, Niels Høiby, Michael Givskov

The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell-cell communication system termed quorum sensing (QS). In the present report it is demonstrated that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient bacteria in vivo is probably a two-sided phenomenon: down regulation of virulence and activation of the innate immune system. These data also suggest that a combination of the action of PMNs and QS inhibitors along with conventional antibiotics would eliminate the biofilm-forming bacteria before a chronic infection is established.

Original languageEnglish
JournalMicrobiology
Volume151
Issue numberPt 2
Pages (from-to)373-83
Number of pages11
ISSN1350-0872
DOIs
Publication statusPublished - Feb 2005

    Research areas

  • Animals, Anti-Bacterial Agents, Bacterial Proteins, Biofilms, Cystic Fibrosis, DNA-Binding Proteins, Female, Gene Expression Regulation, Bacterial, Humans, Hydrogen Peroxide, Mice, Mice, Inbred BALB C, Neutrophils, Pseudomonas Infections, Pseudomonas aeruginosa, Signal Transduction, Tobramycin, Trans-Activators, Virulence, Journal Article, Research Support, Non-U.S. Gov't

ID: 182092079