title: RpiR homologues may link Staphylococcus aureus RNAIII synthesis and pentose phosphate pathway regulation.
abstract: Staphylococcus aureus is a medically important pathogen that synthesizes a wide range of virulence determinants. The synthesis of many staphylococcal virulence determinants is regulated in part by stress-induced changes in the activity of the tricarboxylic acid (TCA) cycle. One metabolic change associated with TCA cycle stress is an increased concentration of ribose, leading us to hypothesize that a pentose phosphate pathway (PPP)-responsive regulator mediates some of the TCA cycle-dependent regulatory effects. Using bioinformatics, we identified three potential ribose-responsive regulators that belong to the RpiR family of transcriptional regulators. To determine whether these RpiR homologues affect PPP activity and virulence determinant synthesis, the rpiR homologues were inactivated, and the effects on PPP activity and virulence factor synthesis were assessed. Two of the three homologues (RpiRB and RpiRC) positively influence the transcription of the PPP genes rpiA and zwf, while the third homologue (RpiRA) is slightly antagonistic to the other homologues. In addition, inactivation of RpiRC altered the temporal transcription of RNAIII, the effector molecule of the agr quorum-sensing system. These data confirm the close linkage of central metabolism and virulence determinant synthesis, and they establish a metabolic override for quorum-sensing-dependent regulation of RNAIII transcription.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska--Lincoln, 155 VBS, Fair St. and East Campus Loop, Lincoln, NE 68583-0905, USA.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Renu
authors.initials: R
authors.lastname: Nandakumar
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Nandakumar
authors.initials: N
authors.lastname: Madayiputhiya
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Rosmarie
authors.initials: R
authors.lastname: Gaupp
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010427:Pentose Phosphate Pathway; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D014157:Transcription Factors