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Biofilm formation by Pseudomonas aeruginosa: role of the C4-HSL cell-to-cell signal and inhibition by azithromycin

Published in Journal of Antimicrobial Chemotherapy. 2003, vol. 52, no. 4, p. 598-604
Abstract OBJECTIVES: In Pseudomonas aeruginosa, biofilm formation is controlled by a cell-to-cell signalling circuit relying on the secretion of 3-oxo-C12-HSL and C4-HSL. Previous studies suggested that C4-HSL plays no significant role in biofilm formation. However the wild-type PAO1 strain PAO-BI, used as a control in these studies is itself impaired in the production of C4-HSL. We wondered therefore whether the role of C4-HSL in biofilm formation might have been underestimated, and whether azithromycin inhibits biofilm formation by interfering with cell-to-cell signalling. METHODS: We used isogenic mutants of wild-type PAO1 strains PAO-BI and PT5 in a static biofilm model. Biofilm formation was quantified using Crystal Violet staining and exopolysaccharide measurements. RESULTS: Wild-type strain PAO-BI, as a result of its reduced C4-HSL secretion, produced 40% less biofilm compared with the wild-type PAO1 strain PT5. Using isogenic mutants of strain PT5 we have shown that whereas a lasI mutant (deficient in 3-oxo-C12-HSL) produced similar amounts of biofilm to the wild-type, a rhlI mutant (deficient in C4-HSL) produced 70% less biofilm. In the latter strain, biofilm formation could be restored by addition of exogenous C4-HSL. Azithromycin, known to reduce the production of both 3-oxo-C12-HSL and C4-HSL, inhibited biofilm formation of wild-type PT5 by 45%. This inhibition could be reversed by the addition of both cell-to-cell signals. CONCLUSIONS: Our results indicate that C4-HSL also plays a significant role in biofilm formation. Furthermore, we demonstrate the potential of using cell-to-cell signalling blocking agents such as azithromycin to interfere with biofilm formation.
Keywords Azithromycin/ pharmacologyBiofilms/drug effects/ growth & developmentCell Communication/ drug effects/physiologyHumansPseudomonas aeruginosaSignal Transduction/drug effects
PMID: 12951348
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Other version: http://jac.oxfordjournals.org/cgi/reprint/52/4/598.pdf
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FAVRE-BONTE, Sabine Adelaide Eugenie, KOHLER, Thilo, VAN DELDEN, Christian. Biofilm formation by Pseudomonas aeruginosa: role of the C4-HSL cell-to-cell signal and inhibition by azithromycin. In: Journal of Antimicrobial Chemotherapy, 2003, vol. 52, n° 4, p. 598-604. doi: 10.1093/jac/dkg397 https://archive-ouverte.unige.ch/unige:7205

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Deposited on : 2010-06-21

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