title: Various checkpoints prevent the synthesis of Staphylococcus aureus peptidoglycan hydrolase LytM in the stationary growth phase.
abstract: In Staphylococcus aureus, peptidoglycan metabolism plays a role in the host inflammatory response and pathogenesis. Transcription of the peptidoglycan hydrolases is activated by the essential 2-component system WalKR at low cell density. During stationary growth phase, WalKR is not active and transcription of the peptidoglycan hydrolase genes is repressed. In this work, we studied regulation of expression of the glycylglycine endopeptidase LytM. We show that, in addition to the transcriptional regulation mediated by WalKR, the synthesis of LytM is negatively controlled by a unique mechanism at the stationary growth phase. We have identified 2 different mRNAs encoding lytM, which vary in the length of their 5' untranslated (5'UTR) regions. LytM is predominantly produced from the WalKR-regulated mRNA transcript carrying a short 5'UTR. The lytM mRNA is also transcribed as part of a polycistronic operon with the upstream SA0264 gene and is constitutively expressed. Although SA0264 protein can be synthesized from the longer operon transcript, lytM cannot be translated because its ribosome-binding site is sequestered into a translationally inactive secondary structure. In addition, the effector of the agr system, RNAIII, can inhibit translation of lytM present on the operon without altering the transcript level but does not have an effect on the translation of the upstream gene. We propose that this dual regulation of lytM expression, at the transcriptional and post-transcriptional levels, contributes to prevent cell wall damage during the stationary phase of growth.
authors.affiliation: a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC , 15 rue René Descartes, Strasbourg , France.
authors.forename: Efthimia
authors.initials: E
authors.lastname: Lioliou
authors.affiliation: a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC , 15 rue René Descartes, Strasbourg , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fechter
authors.affiliation: a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC , 15 rue René Descartes, Strasbourg , France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Caldelari
authors.affiliation: b Institute of Systems and Synthetic Biology, University of Evry-Val-d'Essonne, CNRS FRE3561 , Evry , France.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jester
authors.affiliation: c Unité de Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur , 28 rue du Dr Roux, Paris , France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dubrac
authors.affiliation: a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC , 15 rue René Descartes, Strasbourg , France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Helfer
authors.affiliation: d CIRI, Center International de Recherche en Infectiologie - Inserm U1111 - Université Lyon 1 - Ecole Normale Supérieure de Lyon - CNRS UMR5308 , 21 Avenue Tony Garnier, LYON cedex 07 , France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boisset
authors.affiliation: d CIRI, Center International de Recherche en Infectiologie - Inserm U1111 - Université Lyon 1 - Ecole Normale Supérieure de Lyon - CNRS UMR5308 , 21 Avenue Tony Garnier, LYON cedex 07 , France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: a Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC , 15 rue René Descartes, Strasbourg , France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Romby
authors.affiliation: d CIRI, Center International de Recherche en Infectiologie - Inserm U1111 - Université Lyon 1 - Ecole Normale Supérieure de Lyon - CNRS UMR5308 , 21 Avenue Tony Garnier, LYON cedex 07 , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geissmann
mesh_terms: D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000254:growth & development
chemical_list: D012333:RNA, Messenger; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: Autolysin; LytM; RNAIII; Staphylococcus aureus; cell wall; peptidoglycan; peptidoglycan hydrolase; post-transcriptional regulation