title: Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites.
abstract: Serratia marcescens generates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressed crp mutant phenotypes. Evidence supports that the putative response regulator eepR was directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promoters in vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes.
  
  
  OBJECTIVE
  This study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacterium Serratia marcescens to produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allow S. marcescens to compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Stella
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Roni M
authors.initials: RM
authors.lastname: Lahr
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Brothers
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kalivoda
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Hunt
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kwak
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA shanksrm@upmc.edu.
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism*; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism*; D047630:Depsipeptides / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006461:Hemolysis; D006801:Humans; D008969:Molecular Sequence Data; D009068:Movement; D009154:Mutation; D012706:Serratia marcescens / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D002373:Cyclic AMP Receptor Protein; D047630:Depsipeptides; D014157:Transcription Factors; C009246:serratamolide; D000242:Cyclic AMP