title: Tricarboxylic acid cycle-dependent regulation of Staphylococcus epidermidis polysaccharide intercellular adhesin synthesis.
abstract: Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e.g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis, polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and sigma(B)) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis, resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth into PIA biosynthesis. These data demonstrate that the bacterial metabolic status is a critical regulatory determinant of PIA synthesis. In addition, these data lead us to propose that the TCA cycle acts as a signal transduction pathway to translate external environmental cues into intracellular metabolic signals that modulate the activity of transcriptional regulators.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, 155 VBS, Fair St. and East Campus Loop, Lincoln, NE 68583-0905, USA.
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Michael E
authors.initials: ME
authors.lastname: Olson
authors.forename: Steven
authors.initials: S
authors.lastname: Halouska
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fey
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
mesh_terms: D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002951:Citrates; D002952:Citric Acid Cycle / Q000502:physiology*; D003470:Culture Media; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D020868:Gene Silencing; D009154:Mutation; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013995:Time
chemical_list: D001426:Bacterial Proteins; D002951:Citrates; D003470:Culture Media; D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin; C007744:fluorocitrate; D000154:Aconitate Hydratase