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

被引:162
作者
Favre-Bonté, S [1 ]
Köhler, T [1 ]
Van Delden, C [1 ]
机构
[1] Univ Geneva, CMU, Dept Genet & Microbiol, CH-1211 Geneva 4, Switzerland
关键词
quorum sensing; autoinducers; homoserine-lactones; 3-oxo-C-12-HSL;
D O I
10.1093/jac/dkg397
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: In Pseudomonas aeruginosa, biofilm formation is controlled by a cell-to-cell signalling circuit relying on the secretion of 3-oxo-C-12-HSL and C-4-HSL. Previous studies suggested that C-4-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 C-4-HSL. We wondered therefore whether the role of C-4-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 C-4-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-C-12-HSL) produced similar amounts of biofilm to the wild-type, a rhlI mutant (deficient in C-4-HSL) produced 70% less biofilm. In the latter strain, biofilm formation could be restored by addition of exogenous C-4-HSL. Azithromycin, known to reduce the production of both 3-oxo-C-12-HSL and C-4-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 C-4-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.
引用
收藏
页码:598 / 604
页数:7
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