Physics

Transcriptional regulation

Bacteria

Transcription factor

Biology

Promoter

Gene

Optics

Quorum sensing

Gene expression

Chromatin immunoprecipitation

Genome

Regulation of gene expression

Crosstalk

Pseudomonas aeruginosa

Regulon

Gene regulatory network

Computational biology

Genetics

Virulence

Nature Communications

The virulence of Pseudomonas aeruginosa , a Gram-negative opportunistic pathogen, is regulated by many transcriptional factors (TFs) that control the expression of quorum sensing and protein secretion systems. Here, we report a genome-wide, network-based approach to dissect the crosstalk between 20 key virulence-related TFs. Using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), as well as RNA-seq, we identify 1200 TF-bound genes and 4775 differentially expressed genes. We experimentally validate 347 of these genes as functional target genes, and describe the regulatory relationships of the 20 TFs with their targets in a network that we call ‘ Pseudomonas aeruginosa genomic regulatory network’ (PAGnet). Analysis of the network led to the identification of novel functions for two TFs (ExsA and GacA) in quorum sensing and nitrogen metabolism. Furthermore, we present an online platform and R package based on PAGnet to facilitate updating and user-customised analyses.

An integrated genomic regulatory network of virulence-related transcriptional factors in Pseudomonas aeruginosa