Quinolone signaling in the cell-to-cell communication system of <i>Pseudomonas</i> <i>aeruginosa</i>

Proceedings of the National Academy of Sciences of the United States of America - Tập 96 Số 20 - Trang 11229-11234 - 1999
Everett C. Pesci1, Jared B. J. Milbank1, James P. Pearson1,2, Susan L. McKnight1, Andrew S. Kende1, E. Peter Greenberg1, Barbara H. Iglewski1
1Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858; Department of Chemistry, University of Rochester, Rochester, NY 14627; Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; and Department of Microbiology, University of Iowa, Iowa City, IA 52242
2Protein Design Labs, Inc.

Tóm tắt

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa , which contains two quorum sensing systems ( las and rhl ) that operate via the autoinducers, N -(3-oxododecanoyl)- l -homoserine lactone and N -butyryl- l -homoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB , which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 96 Số 20

11229-11234

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