title: Using NMR metabolomics to investigate tricarboxylic acid cycle-dependent signal transduction in Staphylococcus epidermidis.
abstract: Staphylococcus epidermidis is a skin-resident bacterium and a major cause of biomaterial-associated infections. The transition from residing on the skin to residing on an implanted biomaterial is accompanied by regulatory changes that facilitate bacterial survival in the new environment. These regulatory changes are dependent upon the ability of bacteria to "sense" environmental changes. In S. epidermidis, disparate environmental signals can affect synthesis of the biofilm matrix polysaccharide intercellular adhesin (PIA). Previously, we demonstrated that PIA biosynthesis is regulated by tricarboxylic acid (TCA) cycle activity. The observations that very different environmental signals result in a common phenotype (i.e. increased PIA synthesis) and that TCA cycle activity regulates PIA biosynthesis led us to hypothesize that S. epidermidis is "sensing" disparate environmental signals through the modulation of TCA cycle activity. In this study, we used NMR metabolomics to demonstrate that divergent environmental signals are transduced into common metabolomic changes that are "sensed" by metabolite-responsive regulators, such as CcpA, to affect PIA biosynthesis. These data clarify one mechanism by which very different environmental signals cause common phenotypic changes. In addition, due to the frequency of the TCA cycle in diverse genera of bacteria and the intrinsic properties of TCA cycle enzymes, it is likely the TCA cycle acts as a signal transduction pathway in many bacteria.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska 68583-0905, USA.
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Steven
authors.initials: S
authors.lastname: Halouska
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Nelson
authors.forename: Lauren W
authors.initials: LW
authors.lastname: Kreimer
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology; D000090463:Iron Deficiencies; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D012329:RNA, Bacterial / Q000235:genetics; D015398:Signal Transduction; D013212:Staphylococcus epidermidis / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002492:Central Nervous System Depressants; D012329:RNA, Bacterial; D000431:Ethanol