Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen
- Andrew L. Goodman1,4,5,
- Massimo Merighi1,4,
- Mamoru Hyodo1,
- Isabelle Ventre2,
- Alain Filloux2,3 and
- Stephen Lory1,6
- 1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2LISM-IBSM-CNRS, Marseille Cedex 20, France;
- 3Imperial College London, Centre for Molecular Microbiology and Infection, London SW7 2AZ, United Kingdom
-
↵ These authors contributed equally to this work
Abstract
The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes over 60 two-component sensor kinases and uses several (including RetS and GacS) to reciprocally regulate the production of virulence factors involved in the development of acute or chronic infections. We demonstrate that RetS modulates the phosphorylation state of GacS by a direct and specific interaction between these two membrane-bound sensors. The RetS–GacS interaction can be observed in vitro, in heterologous systems in vivo, and in P. aeruginosa. This function does not require the predicted RetS phosphorelay residues and provides a mechanism for integrating multiple signals without cross-phosphorylation from sensors to noncognate response regulators. These results suggest that multiple two-component systems found in a single bacterium can form multisensor signaling networks while maintaining specific phosphorelay pathways that remain insulated from detrimental cross-talk.
Keywords
Footnotes
-
↵ Present address: Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA
-
↵ Corresponding author.
↵ E-MAIL stephen_lory{at}hms.harvard.edu; FAX (617) 738-7664.
-
Article is online at http://www.genesdev.org/cgi/doi/10.1101/10.1101/gad.1739009
-
Supplemental material is available at http://www.genesdev.org.
-
- Received September 10, 2008.
- Accepted November 20, 2008.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
