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Stringent response activates quorum sensing and modulates cell density-dependent gene expression in Pseudomonas
C van Delden1, R Comte, A M Bally
1Department of Genetics and Microbiology, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland.
Journal of Bacteriology
|August 22, 2001
Summary
The stringent response, triggered by RelA, activates Pseudomonas aeruginosa quorum sensing and virulence factor production, bypassing normal cell density signals. This discovery reveals a new regulatory pathway influencing bacterial communication and pathogenesis.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Nutrient starvation in Escherichia coli triggers a stringent response via the RelA protein, enhancing RpoS expression.
- Pseudomonas aeruginosa utilizes quorum sensing, linked to RpoS, for virulence factor production, regulated by LasR and RhlR activators and autoinducers.
- Quorum sensing controls virulence factor secretion, such as LasB elastase, in a cell density-dependent manner.
Purpose of the Study:
- To investigate the impact of the stringent response on quorum sensing in Pseudomonas aeruginosa.
- To determine if RelA-mediated stringent response affects RpoS expression and virulence factor production.
- To elucidate the relationship between the stringent response and the activation of quorum-sensing systems.
Main Methods:
- Overexpression of the relA gene in P. aeruginosa.
- Analysis of rpoS gene expression and LasB elastase production.
- Assessment of lasR and rhlR gene expression and autoinducer synthesis under stringent conditions induced by relA overexpression or serine hydroxamate (SHX).
- Experiments utilizing a PAO1 rpoS mutant strain.
Main Results:
- RelA overexpression in P. aeruginosa led to increased rpoS expression and premature, cell density-independent LasB elastase production.
- The stringent response, induced by relA overexpression, resulted in premature activation of both lasR and rhlR gene expression and autoinducer synthesis.
- Premature lasR and rhlR expression occurred even in a PAO1 rpoS mutant overexpressing relA.
- SHX-induced stringent response also caused premature 3-oxo-C(12)-HSL autoinducer production, an effect absent in a relA mutant.
Conclusions:
- The stringent response, mediated by RelA, can activate the quorum-sensing systems (LasR/RhlR) in P. aeruginosa.
- This activation leads to premature virulence factor production, independent of normal cell density signaling.
- The stringent response provides a mechanism to bypass cell density-dependent regulation of quorum sensing and virulence in P. aeruginosa.