RNA target profiles direct the discovery of virulence functions for the cold-shock proteins CspC and CspE

Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):6824-6829. doi: 10.1073/pnas.1620772114. Epub 2017 Jun 13.


The functions of many bacterial RNA-binding proteins remain obscure because of a lack of knowledge of their cellular ligands. Although well-studied cold-shock protein A (CspA) family members are induced and function at low temperature, others are highly expressed in infection-relevant conditions. Here, we have profiled transcripts bound in vivo by the CspA family members of Salmonella enterica serovar Typhimurium to link the constitutively expressed CspC and CspE proteins with virulence pathways. Phenotypic assays in vitro demonstrated a crucial role for these proteins in membrane stress, motility, and biofilm formation. Moreover, double deletion of cspC and cspE fully attenuates Salmonella in systemic mouse infection. In other words, the RNA ligand-centric approach taken here overcomes a problematic molecular redundancy of CspC and CspE that likely explains why these proteins have evaded selection in previous virulence factor screens in animals. Our results highlight RNA-binding proteins as regulators of pathogenicity and potential targets of antimicrobial therapy. They also suggest that globally acting RNA-binding proteins are more common in bacteria than currently appreciated.

Keywords: RNA-binding protein; Salmonella; bacterial pathogenesis; cold-shock protein; stress response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Cold Shock Proteins and Peptides* / chemistry
  • Cold Shock Proteins and Peptides* / genetics
  • Cold Shock Proteins and Peptides* / metabolism
  • Escherichia coli
  • Female
  • Heat-Shock Proteins* / chemistry
  • Heat-Shock Proteins* / genetics
  • Heat-Shock Proteins* / metabolism
  • Mice, Inbred BALB C
  • RNA-Binding Proteins* / chemistry
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Salmonella Infections* / genetics
  • Salmonella Infections* / metabolism
  • Salmonella typhimurium* / chemistry
  • Salmonella typhimurium* / genetics
  • Salmonella typhimurium* / metabolism
  • Salmonella typhimurium* / pathogenicity
  • Virulence Factors* / chemistry
  • Virulence Factors* / genetics
  • Virulence Factors* / metabolism


  • Bacterial Proteins
  • Cold Shock Proteins and Peptides
  • CspC protein, bacteria
  • Heat-Shock Proteins
  • RNA-Binding Proteins
  • Virulence Factors