title: A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella.
abstract: BACKGROUND
  Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined.
  
  
  RESULTS
  Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation.
  
  
  CONCLUSIONS
  We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.
authors.affiliation: Department of Advanced Bioscience, Graduate School of Agriculture, Kinki University, Nakamachi, Nara, Japan. kato_a@nara.kindai.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Kato
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Nomura
authors.forename: Haruka
authors.initials: H
authors.lastname: Emori
authors.forename: Kei
authors.initials: K
authors.lastname: Hagihara
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Utsumi
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005820:Genetic Testing; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids; D060066:Protein Interaction Maps; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C069567:sigma factor KatF protein, Bacteria; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C092472:CpxA protein, bacteria