Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen

TLDR

Pseudomonas aeruginosa possesses more than 60 two‑component sensor kinases, with RetS and GacS reciprocally regulating virulence factor production that drives acute or chronic infection. RetS directly interacts with GacS to modulate its phosphorylation, a mechanism that integrates signals without cross‑phosphorylation and shows that multiple two‑component systems can form insulated multisensor networks in P.

Abstract

The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes over 60 two-component sensor kinases and uses several (including RetS and GacS) to reciprocally regulate the production of virulence factors involved in the development of acute or chronic infections. We demonstrate that RetS modulates the phosphorylation state of GacS by a direct and specific interaction between these two membrane-bound sensors. The RetS–GacS interaction can be observed in vitro, in heterologous systems in vivo, and in P. aeruginosa . This function does not require the predicted RetS phosphorelay residues and provides a mechanism for integrating multiple signals without cross-phosphorylation from sensors to noncognate response regulators. These results suggest that multiple two-component systems found in a single bacterium can form multisensor signaling networks while maintaining specific phosphorelay pathways that remain insulated from detrimental cross-talk.