title: Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Goodman
authors.forename: Massimo
authors.initials: M
authors.lastname: Merighi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ventre
authors.forename: Alain
authors.initials: A
authors.lastname: Filloux
authors.forename: Stephen
authors.initials: S
authors.lastname: Lory
mesh_terms: D000208:Acute Disease; D001426:Bacterial Proteins / Q000378:metabolism; D002908:Chronic Disease; D003593:Cytoplasm; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000472:pathogenicity*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C091100:GacA protein, Bacteria; C507835:RetS protein, Pseudomonas aeruginosa; D014157:Transcription Factors; D011494:Protein Kinases; C074165:lemA protein, bacterial