title: CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis.
abstract: Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR-LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were constructed in strain 1457 and 1457-acnA and the effects on TCA cycle activity, biofilm formation and virulence were assessed. As anticipated, deletion of ccpA derepressed TCA cycle activity and inhibited biofilm formation; however, ccpA deletion had only a modest effect on icaADBC transcription. Surprisingly, deletion of ccpA in strain 1457-acnA, a strain whose TCA cycle is inactive and where icaADBC transcription is derepressed, strongly inhibited icaADBC transcription. These observations demonstrate that CcpA is a positive effector of biofilm formation and icaADBC transcription and a repressor of TCA cycle activity.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Hartmann
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Theodoric A
authors.initials: TA
authors.lastname: Mattes
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Hiatt
authors.affiliation: Division of Infection Biology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Naja J
authors.initials: NJ
authors.lastname: Jann
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Nagender
authors.initials: N
authors.lastname: Ledala
authors.affiliation: Division of Infection Biology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002952:Citric Acid Cycle / Q000235:genetics*; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D012097:Repressor Proteins; C069286:catabolite control proteins, bacteria; C113579:polysaccharide intercellular adhesin