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Julian Trouillon

Insights into the regulatory networks of Pseudomonas aeruginosa

Published on 13 November 2020
Thesis presented November 13, 2020

Abstract:
Pseudomonas aeruginosa is an opportunistic human pathogen and a leading cause of nosocomial infections. This Gram-negative bacterium possesses one of the most complex regulatory networks, which allows it to sense and adapt to a wide variety of environmental conditions. In this work, several aspects of P. aeruginosa regulation were investigated. A new transcription factor (TF), ErfA, was found involved in the regulation of the ExlBA-dependent virulence in the PA7-like lineage of P. aeruginosa strains. The study of exlBA regulation in several Pseudomonas species revealed a diversity of regulatory mechanisms for this virulence factor due to differences in promoter cis-regulatory elements, which illustrated a mechanism of regulatory network evolution between closely related species. This type of promoter diversity was further investigated at a genome-wide scale and was found to be very common across all genes. Additionally, the characterization of all regulators sharing ErfA domain architecture allowed the definition of this family of TFs as comprising local, specialized regulators involved in the inhibition of small metabolic pathways. To go further into P. aeruginosa transcriptional regulation, the genome-wide determination of the regulons of all DNA-binding response regulators allowed the delineation of the two-component systems regulatory network, which comprises more than half of all genes of the bacterium. Finally, the investigation of post-transcriptional regulation through the comparative determination of RNA interactomes of Hfq between strains and growth phases identified numerous new common or specific regulatory interactions.

Keywords:
Transcription factors, regulation, regulatory networks, Pseudomonas, virulence