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Journal of Bacteriology, November 2001, p. 6676-6683, Vol. 183, No. 22
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.22.6676-6683.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Global Posttranscriptional Regulator RsmA Modulates Production of Virulence Determinants and N-Acylhomoserine Lactones in Pseudomonas aeruginosa

Gabriella Pessi,^1, Faye Williams,^2,3 Zoë Hindle,^2, Karin Heurlier,¹ Matthew T. G. Holden,^2,3,§ Miguel Cámara,² Dieter Haas,¹ and Paul Williams^2,3,*

Laboratoire de Biologie Microbienne, Université de Lausanne, CH-1015 Lausanne, Switzerland,¹ and School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD,² and Institute of Infections and Immunity, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH,³ United Kingdom

Received 12 April 2001/Accepted 20 August 2001

Posttranscriptional control is known to contribute to the regulation of secondary metabolism and virulence determinants in certain gram-negative bacteria. Here we report the isolation of a Pseudomonas aeruginosa gene which encodes a global translational regulatory protein, RsmA (regulator of secondary metabolites). Overexpression of rsmA resulted in a substantial reduction in the levels of extracellular products, including protease, elastase, and staphylolytic (LasA protease) activity as well as the PA-IL lectin, hydrogen cyanide (HCN), and the phenazine pigment pyocyanin. While inactivation of rsmA in P. aeruginosa had only minor effects on the extracellular enzymes and the PA-IL lectin, the production of HCN and pyocyanin was enhanced during the exponential phase. The influence of RsmA on N-acylhomoserine lactone-mediated quorum sensing was determined by assaying the levels of N-(3-oxododecanoyl)homoserine lactone (3-oxo-C12-HSL) and N-butanoylhomoserine lactone (C4-HSL) produced by the rsmA mutant and the rsmA-overexpressing strain. RsmA exerted a negative effect on the synthesis of both 3-oxo-C12-HSL and C4-HSL, which was confirmed by using lasI and rhlI translational fusions. These data also highlighted the temporal expression control of the lasI gene, which was induced much earlier and to a higher level during the exponential growth phase in an rsmA mutant. To investigate whether RsmA modulates HCN production solely via quorum-sensing control, hcn translational fusions were employed to monitor the regulation of the cyanide biosynthesis genes (hcnABC). RsmA was shown to exert an additional negative effect on cyanogenesis posttranscriptionally by acting on a region surrounding the hcnA ribosome-binding site. This suggests that, in P. aeruginosa, RsmA functions as a pleiotropic posttranscriptional regulator of secondary metabolites directly and also indirectly by modulating the quorum-sensing circuitry.

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^* Corresponding author. Mailing address: School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. Phone: 44 115 9515047. Fax: 44 115 8466296. E-mail: paul.williams{at}nottingham.ac.uk.

Present address: Nestlé Research Center, CH-1000 Lausanne 26, Switzerland.

Present address: Microscience Ltd., Wokingham, Berks., RG41 5TU, United Kingdom.

^§ Present address: The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.

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Journal of Bacteriology, November 2001, p. 6676-6683, Vol. 183, No. 22
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.22.6676-6683.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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