title: Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia.
abstract: Most bacterial small RNAs (sRNAs) are post-transcriptional regulators involved in adaptive responses, controlling gene expression by modulating translation or stability of their target mRNAs often in concert with the RNA chaperone Hfq. Neisseria meningitides, the leading cause of bacterial meningitis, is able to adapt to different host niches during human infection. However, only a few sRNAs and their functions have been fully described to date. Recently, transcriptional expression profiling of N. meningitides in human blood ex vivo revealed 91 differentially expressed putative sRNAs. Here we expanded this analysis by performing a global transcriptome study after exposure of N. meningitides to physiologically relevant stress signals (e.g. heat shock, oxidative stress, iron and carbon source limitation). and we identified putative sRNAs that were differentially expressed in vitro. A set of 98 putative sRNAs was obtained by analyzing transcriptome data and 8 new sRNAs were validated, both by Northern blot and by primer extension techniques. Deletion of selected sRNAs caused attenuation of N. meningitides infection in the in vivo infant rat model, leading to the identification of the first sRNAs influencing meningococcal bacteremia. Further analysis indicated that one of the sRNAs affecting bacteremia responded to carbon source availability through repression by a GntR-like transcriptional regulator. Both the sRNA and the GntR-like regulator are implicated in the control of gene expression from a common network involved in energy metabolism.
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Fagnocchi
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bottini
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Golfieri
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fantappiè
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferlicca
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Guadagnuolo
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Del Tordello
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Siena
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scarlato
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.affiliation: Novartis Vaccines and Diagnotics, Siena, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Delany
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000097:blood*; D015152:Blotting, Northern; D009345:Neisseria meningitidis / Q000302:isolation & purification*; D012329:RNA, Bacterial / Q000235:genetics*; D051381:Rats; D059467:Transcriptome
chemical_list: D012329:RNA, Bacterial