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Journal of Bacteriology, September 2001, p. 5376-5384, Vol. 183, No. 18
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.18.5376-5384.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Stringent Response Activates Quorum Sensing and Modulates Cell Density-Dependent Gene Expression in Pseudomonas aeruginosa

Christian van Delden,1 Rachel Comte,1 and And Marc Bally2,*

Department of Genetics and Microbiology, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland,1 and Laboratoire d'Ingénierie des Systèmes Macromoléculaires, Centre National de la Recherche Scientifique, F-13402 Marseille cedex 20, France2

Received 20 February 2001/Accepted 26 June 2001

During nutrient starvation, Escherichia coli elicits a stringent response involving the ribosome-associated protein RelA. Activation of RelA results in a global change in the cellular metabolism including enhanced expression of the stationary-phase sigma factor RpoS. In the human pathogen Pseudomonas aeruginosa, a complex quorum-sensing circuitry, linked to RpoS expression, is required for cell density-dependent production of many secreted virulence factors, including LasB elastase. Quorum sensing relies on the activation of specific transcriptional regulators (LasR and RhlR) by their corresponding autoinducers (3-oxo-C12-homoserine lactone [HSL] and C4-HSL), which function as intercellular signals. We found that overexpression of relA activated the expression of rpoS in P. aeruginosa and led to premature, cell density-independent LasB elastase production. We therefore investigated the effects of the stringent response on quorum sensing. Both lasR and rhlR gene expression and autoinducer synthesis were prematurely activated during the stringent response induced by overexpression of relA. Premature expression of lasR and rhlR was also observed when relA was overexpressed in a PAO1 rpoS mutant. The stringent response induced by the amino acid analogue serine hydroxamate (SHX) also led to premature production of the 3-oxo-C12-HSL autoinducer. This response to SHX was absent in a PAO1 relA mutant. These findings suggest that the stringent response can activate the two quorum-sensing systems of P. aeruginosa independently of cell density.

* Corresponding author. Mailing address: Centre d'Océanologie de Marseille, UMR 6540, Station Marine d'Endoume, chemin de la Batterie des Lions, F-13007 Marseille, France. Phone: 33 491 041634. Fax: 33 491 041635. E-mail: bally{at}com.univ-mrs.fr.

Journal of Bacteriology, September 2001, p. 5376-5384, Vol. 183, No. 18
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.18.5376-5384.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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