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

TY - JOUR

T1 - Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

AU - Maudet, Claire

AU - Mano, Miguel

AU - Sunkavalli, Ushasree

AU - Sharan, Malvika

AU - Giacca, Mauro

AU - Förstner, Konrad U.

AU - Eulalio, Ana

PY - 2014/8/22

Y1 - 2014/8/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907343849&partnerID=8YFLogxK

U2 - 10.1038/ncomms5718

DO - 10.1038/ncomms5718

M3 - Article

C2 - 25146723

AN - SCOPUS:84907343849

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4718

ER -