Increasing evidence suggests an important role for miRNAs in the molecular interplay
between bacterial pathogens and host cells. Here we perform a fluorescence microscopybased
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.
