Systematic Reconstruction of the Complete Two-Component Sensorial Network in Staphylococcus aureus

Andreas Haag, Beatriz Rapun-Araiz, Virginia De Cesare, Pedro Dorado-Morales, José Penadés, Iñigo Lasa

Research output: Contribution to conferencePoster


In bacteria, adaptation to changes in the environment is mainly controlled through two-component signal transduction systems (TCSs). Most bacteria contain dozens of TCSs, each of them responsible for sensing a different range of signals and controlling the expression of a repertoire of target genes (regulon). Frequently, TCS control key physiological changes required for pathogenesis and/or antimicrobial resistance. Over the years, identification of the regulon controlled by each individual TCS in different bacteria has been a recurrent question. However, limitations associated with the classical approaches used have left our knowledge far from complete. In this report, using a pioneering approach in which a strain devoid of the complete nonessential TCS network was systematically complemented with the constitutively active form of each response regulator, we have reconstituted the regulon of each TCS of S. aureus in the absence of interference between members of the family. Transcriptome sequencing (RNA-Seq) and proteomics allowed us to determine the size, complexity, and insulation of each regulon and to identify the genes regulated exclusively by one or many TCSs. This gain-of-function strategy provides the first description of the complete TCS regulon in a living cell, which we expect will be useful to understand the pathobiology of this important pathogen.
Original languageUndefined/Unknown
Number of pages1
Publication statusPublished - 27 May 2022

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