Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia

PLoS One. 2015 May 7;10(5):e0126325. doi: 10.1371/journal.pone.0126325. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / blood*
  • Blotting, Northern
  • Neisseria meningitidis / isolation & purification*
  • RNA, Bacterial / genetics*
  • Rats
  • Transcriptome*

Substances

  • RNA, Bacterial

Grants and funding

L. Fagnocchi, GG and SG are recipients of a Novartis fellowship from the Ph.D. program in Functional Biology of Molecular and Cellular Systems of the University of Bologna. SB is recipient of a Novartis fellowship from the Ph.D. program of the University of Siena. The authors FF, EDT, ES, DS, AM, and ID are employed by the funding organization, Novartis, that provided support in the form of salaries for said authors and fellowships associated with the universities. The specific roles of these authors are articulated in the author contributions section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.