title: The CtrA phosphorelay integrates differentiation and communication in the marine alphaproteobacterium Dinoroseobacter shibae.
abstract: BACKGROUND
  Dinoroseobacter shibae, a member of the Roseobacter clade abundant in marine environments, maintains morphological heterogeneity throughout growth, with small cells dividing by binary fission and large cells dividing by budding from one or both cell poles. This morphological heterogeneity is lost if the quorum sensing (QS) system is silenced, concurrent with a decreased expression of the CtrA phosphorelay, a regulatory system conserved in Alphaproteobacteria and the master regulator of the Caulobacter crescentus cell cycle. It consists of the sensor histidine kinase CckA, the phosphotransferase ChpT and the transcriptional regulator CtrA. Here we tested if the QS induced differentiation of D. shibae is mediated by the CtrA phosphorelay.
  
  
  RESULTS
  Mutants for ctrA, chpT and cckA showed almost homogeneous cell morphology and divided by binary fission. For ctrA and chpT, expression in trans on a plasmid caused the fraction of cells containing more than two chromosome equivalents to increase above wild-type level, indicating that gene copy number directly controls chromosome number. Transcriptome analysis revealed that CtrA is a master regulator for flagellar biosynthesis and has a great influence on the transition to stationary phase. Interestingly, the expression of the autoinducer synthase genes luxI2 and luxI3 was strongly reduced in all three mutants, resulting in loss of biosynthesis of acylated homoserine-lactones with C14 side-chain, but could be restored by expressing these genes in trans. Several phylogenetic clusters of Alphaproteobacteria revealed a CtrA binding site in the promoters of QS genes, including Roseobacters and Rhizobia.
  
  
  CONCLUSIONS
  The CtrA phosphorelay induces differentiation of a marine Roseobacter strain that is strikingly different from that of C. crescentus. Instead of a tightly regulated cell cycle and a switch between two morphotypes, the morphology and cell division of Dinoroseobacter shibae are highly heterogeneous. We discovered for the first time that the CtrA phosphorelay controls the biosynthesis of signaling molecules. Thus cell-cell communication and differentiation are interlinked in this organism. This may be a common strategy, since we found a similar genetic set-up in other species in the ecologically relevant group of Alphaproteobacteria. D. shibae will be a valuable model organism to study bacterial differentiation into pleomorphic cells.
authors: Hui
authors: H
authors: Wang
authors: Lisa
authors: L
authors: Ziesche
authors: Oliver
authors: O
authors: Frank
authors: Victoria
authors: V
authors: Michael
authors: Madeleine
authors: M
authors: Martin
authors: Jörn
authors: J
authors: Petersen
authors: Stefan
authors: S
authors: Schulz
authors: Irene
authors: I
authors: Wagner-Döbler
authors: Helmholtz-Centre for Infection Research (HZI), Group of Microbial Communication, Braunschweig, Germany. juergen.tomasch@helmholtz-hzi.de.
authors: Jürgen
authors: J
authors: Tomasch
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D019143:Evolution, Molecular; D005810:Multigene Family; D010641:Phenotype; D011401:Promoter Regions, Genetic; D053038:Quorum Sensing / Q000235:genetics; D041902:Rhodobacteraceae / Q000235:genetics* / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; C085427:LuxI protein, Bacteria; D014157:Transcription Factors