Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen.
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.
Goodman
Andrew L
AL
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Merighi
Massimo
M
Hyodo
Mamoru
M
Ventre
Isabelle
I
Filloux
Alain
A
Lory
Stephen
S
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
D001426:Bacterial Proteins; C091100:GacA protein, Bacteria; C507835:RetS protein, Pseudomonas aeruginosa; D014157:Transcription Factors; D011494:Protein Kinases; C074165:lemA protein, bacterial