title: Regulation of neuraminidase expression in Streptococcus pneumoniae.
abstract: BACKGROUND
  Sialic acid (N-acetylneuraminic acid; NeuNAc) is one of the most important carbohydrates for Streptococcus pneumoniae due of its role as a carbon and energy source, receptor for adhesion and invasion and molecular signal for promotion of biofilm formation, nasopharyngeal carriage and invasion of the lung.
  
  
  RESULTS
  In this work, NeuNAc and its metabolic derivative N-acetyl mannosamine (ManNAc) were used to analyze regulatory mechanisms of the neuraminidase locus expression. Genomic and metabolic comparison to Streptococcus mitis, Streptococcus oralis, Streptococcus gordonii and Streptococcus sanguinis elucidates the metabolic association of the two amino sugars to different parts of the locus coding for the two main pneumococcal neuraminidases and confirms the substrate specificity of the respective ABC transporters. Quantitative gene expression analysis shows repression of the locus by glucose and induction of all predicted transcriptional units by ManNAc and NeuNAc, each inducing with higher efficiency the operon encoding for the transporter with higher specificity for the respective amino sugar. Cytofluorimetric analysis demonstrated enhanced surface exposure of NanA on pneumococci grown in NeuNAc and ManNAc and an activity assay allowed to quantify approximately twelve times as much neuraminidase activity on induced cells as opposed to glucose grown cells.
  
  
  CONCLUSIONS
  The present data increase the understanding of metabolic regulation of the nanAB locus and indicate that experiments aimed at the elucidation of the relevance of neuraminidases in pneumococcal virulence should possibly not be carried out on bacteria grown in glucose containing media.
authors.affiliation: Dipartimento di Biotecnologie, Università di Siena, Siena, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Gualdi
authors.forename: Jasvinder Kaur
authors.initials: JK
authors.lastname: Hayre
authors.forename: Alice
authors.initials: A
authors.lastname: Gerlini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bidossi
authors.forename: Leonarda
authors.initials: L
authors.lastname: Colomba
authors.forename: Claudia
authors.initials: C
authors.lastname: Trappetti
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Docquier
authors.forename: Peter
authors.initials: P
authors.lastname: Andrew
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
mesh_terms: D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000096:biosynthesis*; D009876:Operon; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006595:Hexosamines; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; C002022:N-acetylmannosamine