Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

Nat Commun. 2014 Aug 22;5:4718. doi: 10.1038/ncomms5718.


Increasing evidence suggests an important role for miRNAs in the molecular interplay between bacterial pathogens and host cells. Here we perform a fluorescence microscopy-based screen using a library of miRNA mimics and demonstrate that miRNAs modulate Salmonella infection. Several members of the miR-15 miRNA family were among the 17 miRNAs that more efficiently inhibit Salmonella infection. We discovered that these miRNAs are downregulated during Salmonella infection, through the inhibition of the transcription factor E2F1. Analysis of miR-15 family targets revealed that derepression of cyclin D1 and the consequent promotion of G1/S transition are crucial for Salmonella intracellular proliferation. In addition, Salmonella induces G2/M cell cycle arrest in infected cells, further promoting its replication. Overall, these findings uncover a mechanism whereby Salmonella renders host cells more susceptible to infection by controlling cell cycle progression through the active modulation of host cell miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Cyclin D1 / genetics
  • E2F1 Transcription Factor / genetics
  • Gene Expression Regulation
  • HeLa Cells / drug effects
  • HeLa Cells / microbiology
  • High-Throughput Nucleotide Sequencing / methods
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mice
  • MicroRNAs / genetics*
  • Multigene Family
  • RAW 264.7 Cells / microbiology
  • Salmonella Infections / genetics*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / pathogenicity


  • CCND1 protein, human
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Lipopolysaccharides
  • MIRN15 microRNA, human
  • MicroRNAs
  • Cyclin D1

Associated data

  • GEO/GSE53281