title: A non-coding RNA promotes bacterial persistence and decreases virulence by regulating a regulator in Staphylococcus aureus.
abstract: Staphylococcus aureus produces a high number of RNAs for which the functions are poorly understood. Several non-coding RNAs carry a C-rich sequence suggesting that they regulate mRNAs at the post-transcriptional level. We demonstrate that the Sigma B-dependent RsaA RNA represses the synthesis of the global transcriptional regulator MgrA by forming an imperfect duplex with the Shine and Dalgarno sequence and a loop-loop interaction within the coding region of the target mRNA. These two recognition sites are required for translation repression. Consequently, RsaA causes enhanced production of biofilm and a decreased synthesis of capsule formation in several strain backgrounds. These phenotypes led to a decreased protection of S. aureus against opsonophagocytic killing by polymorphonuclear leukocytes compared to the mutant strains lacking RsaA. Mice animal models showed that RsaA attenuates the severity of acute systemic infections and enhances chronic catheter infection. RsaA takes part in a regulatory network that contributes to the complex interactions of S. aureus with the host immune system to moderate invasiveness and favour chronic infections. It is the first example of a conserved small RNA in S. aureus functioning as a virulence suppressor of acute infections. Because S. aureus is essentially a human commensal, we propose that RsaA has been positively selected through evolution to support commensalism and saprophytic interactions with the host.
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Romilly
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; Inserm U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Lyon, France; CNRS, UMR5308, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lays
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tomasini
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Caldelari
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; Inserm U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Lyon, France; CNRS, UMR5308, Lyon, France; Hospices Civils de Lyon, Lyon, France.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Benito
authors.affiliation: Plateforme Protéomique IBMC, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hammann
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; Inserm U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Lyon, France; CNRS, UMR5308, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geissmann
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; Inserm U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Lyon, France; CNRS, UMR5308, Lyon, France; Hospices Civils de Lyon, Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boisset
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Romby
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; Inserm U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Lyon, France; CNRS, UMR5308, Lyon, France; Hospices Civils de Lyon, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D055499:Catheter-Related Infections / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006790:Host-Parasite Interactions / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D040901:Proteomics; D012329:RNA, Bacterial / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000235:genetics*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D022661:RNA, Untranslated