Abstract
Two-component systems (TCS) serve as stimulus-response coupling mechanisms to allow organisms to adapt to a variety of environmental conditions. The opportunistic pathogen Pseudomonas aeruginosa encodes for more than 100 TCS components. To avoid unwanted cross-talk, signaling cascades are very specific, with one sensor talking to its cognate response regulator (RR). However, cross-regulation may provide means to integrate different environmental stimuli into a harmonized output response. By applying a split luciferase complementation assay, we identified a functional interaction of two RRs of the OmpR/PhoB subfamily, namely PhoB and TctD in P. aeruginosa. Transcriptional profiling, ChIP-seq analysis and a global motif scan uncovered the regulons of the two RRs as well as a quadripartite binding motif in six promoter regions. Phosphate limitation resulted in PhoB-dependent expression of the downstream genes, whereas the presence of TctD counteracted this activation. Thus, the integration of two important environmental signals e.g. phosphate availability and the carbon source are achieved by a titration of the relative amounts of two phosphorylated RRs that inversely regulate a common subset of genes. In conclusion, our results on the PhoB and TctD mediated two-component signal transduction pathways exemplify how P. aeruginosa may exploit cross-regulation to adapt bacterial behavior to complex environments.
Highlights
Two-component systems consist of a histidine (His) protein kinase that senses a signal input and a response regulator (RR) that mediates the output [1]
Our results indicate that the proteinfragment complementation assay (PCA) can be used to measure OmpR/PhoB subfamily member interactions in P. aeruginosa and we identified a functional interaction of PhoB with the RR TctD in vivo
This variation seems to be due to a difference in the activity of efflux pumps or the permeability of the cell membrane for the GLuc substrate coelenterazine, since testing of cell lysates of both strains did not show a differential in luminescence
Summary
Two-component systems consist of a histidine (His) protein kinase that senses a signal input and a response regulator (RR) that mediates the output [1]. They are ancient and evolutionarily conserved signaling mechanisms and represent the largest family of signaling systems in the bacterial kingdom. Most of the bacterial RRs are two-domain proteins consisting of a receiver module which is fused to a second output or effector activity domain [4]. The great diversity within the sensing domains of the HKs and the effector domains of the RRs allow numerous variations within those two-component systems coupling diverse input stimuli to a wide range of output responses
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