Transcriptomic profiling of Yersinia pseudotuberculosis reveals reprogramming of the Crp regulon by temperature and uncovers Crp as a master regulator of small RNAs

PLoS Genet. 2015 Mar 27;11(3):e1005087. doi: 10.1371/journal.pgen.1005087. eCollection 2015 Mar.

Abstract

One hallmark of pathogenic yersiniae is their ability to rapidly adjust their life-style and pathogenesis upon host entry. In order to capture the range, magnitude and complexity of the underlying gene control mechanisms we used comparative RNA-seq-based transcriptomic profiling of the enteric pathogen Y. pseudotuberculosis under environmental and infection-relevant conditions. We identified 1151 individual transcription start sites, multiple riboswitch-like RNA elements, and a global set of antisense RNAs and previously unrecognized trans-acting RNAs. Taking advantage of these data, we revealed a temperature-induced and growth phase-dependent reprogramming of a large set of catabolic/energy production genes and uncovered the existence of a thermo-regulated 'acetate switch', which appear to prime the bacteria for growth in the digestive tract. To elucidate the regulatory architecture linking nutritional status to virulence we also refined the CRP regulon. We identified a massive remodelling of the CRP-controlled network in response to temperature and discovered CRP as a transcriptional master regulator of numerous conserved and newly identified non-coding RNAs which participate in this process. This finding highlights a novel level of complexity of the regulatory network in which the concerted action of transcriptional regulators and multiple non-coding RNAs under control of CRP adjusts the control of Yersinia fitness and virulence to the requirements of their environmental and virulent life-styles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP / genetics
  • Cyclic AMP / metabolism
  • Cyclic AMP Receptor Protein / genetics*
  • Fungal Proteins / genetics*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Fungal
  • Gene-Environment Interaction
  • RNA, Antisense / genetics
  • RNA, Antisense / isolation & purification
  • Regulon / genetics*
  • Riboswitch / genetics
  • Temperature
  • Transcription Initiation Site
  • Yersinia pseudotuberculosis / genetics*
  • Yersinia pseudotuberculosis / growth & development
  • Yersinia pseudotuberculosis / pathogenicity

Substances

  • Cyclic AMP Receptor Protein
  • Fungal Proteins
  • RNA, Antisense
  • Riboswitch
  • Cyclic AMP

Grants and funding

This work was supported by grants (DE616/4 and 616/5) of the German Research Foundation (DFG) in the Priority Programs SPP1258 and SPP1316, the President’s Initiative and Networking Fund of the Helmholtz Association of German Research Centres (HGF) under contract number VH-GS-202, and the Fonds der Chemischen Industrie. PD is supported by the German Center of Infection Research (DZIF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.