Rewiring of a sigma factor regulatory network in P. aeruginosa by a naturally occurring single nucleotide polymorphism

ABSTRACT: Transcriptional regulatory networks represent an important organizational element in the bacterial cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of gene transcription. How these networks evolve is not well understood, and the effects of natural occurring polymorphisms within network components are often not known. Here, we systematically investigate the functional consequences of an amino acid substitution in the sigma factor protein RpoN in the opportunitic pathogen Pseudomonas aeruginosa. While RpoN is known to be important for virulence gene expression in P. aeruginosa, the particular amino acid substitution is important for ecological success of the bacteria in cystic fibrosis infections. We use Chromatin Immunoprecipitation coupled to deep sequencing (ChIP-seq), transcriptional profiling as well as in vitro protein-DNA interaction studies and show that the rpoN mutation results in reduced connections to only parts of the RpoN controlled regulatory network. On the other hand, the mutation results in activation of other sigma factor regulons. Finally, our results also show that the rpoN mutation results in a rewiring of the RpoN network in terms of increased connectivity and positive regulatory effect on a virulence associated locus. This molecular pleiotropy could not have been predicted from in silico analyses alone, and this work thus underlines the importance of achieving a molecular understanding of the effects of polymorphisms in regulator network components

ORGANISM(S): Pseudomonas aeruginosa

PROVIDER: GSE81573 | GEO | 2019/05/01

REPOSITORIES: GEO