Structure of the RhlR-PqsE complex from Pseudomonas aeruginosa reveals mechanistic insights into quorum-sensing gene regulation

Structure. 2022 Dec 1;30(12):1626-1636.e4. doi: 10.1016/j.str.2022.10.008. Epub 2022 Nov 14.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that is responsible for thousands of deaths every year in the United States. P. aeruginosa virulence factor production is mediated by quorum sensing, a mechanism of bacterial cell-cell communication that relies on the production and detection of signal molecules called autoinducers. In P. aeruginosa, the transcription factor receptor RhlR is activated by a RhlI-synthesized autoinducer. We recently showed that RhlR-dependent transcription is enhanced by a physical interaction with the enzyme PqsE via increased affinity of RhlR for promoter DNA. However, the molecular basis for complex formation and how complex formation enhanced RhlR transcriptional activity remained unclear. Here, we report the structure of ligand-bound RhlR in complex with PqsE. Additionally, we determined the structure of the complex bound with DNA, revealing the mechanism by which RhlR-mediated transcription is enhanced by PqsE, thereby establishing the molecular basis for RhlR-dependent virulence factor production in P. aeruginosa.

Keywords: Pseudomonas aeruginosa; bacterial gene regulation; pathogenesis; protein-protein interaction; quorum sensing; structural biology; transcription.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / metabolism
  • Quorum Sensing* / genetics
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Virulence Factors