Co-component signal transduction systems: Fast-evolving virulence regulation cassettes discovered in enteric bacteria

Lisa N. Kinch, Qian Cong, Jananee Jaishankar, Kim Orth

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Bacterial signal transduction systems sense changes in the environment and transmit these signals to control cellular responses. The simplest one-component signal transduction systems include an input sensor domain and an output response domain encoded in a single protein chain. Alternatively, two-component signal transduction systems transmit signals by phosphorelay between input and output domains from separate proteins. The membrane-tethered periplasmic bile acid sensor that activates the Vibrio parahaemolyticus type III secretion system adopts an obligate heterodimer of two proteins encoded by partially overlapping VtrA and VtrC genes. This co-component signal transduction system binds bile acid using a lipocalin-like domain in VtrC and transmits the signal through the membrane to a cytoplasmic DNA-binding transcription factor in VtrA. Using the domain and operon organization of VtrA/VtrC, we identify a fastevolving superfamily of co-component systems in enteric bacteria. Accurate machine learning-based fold predictions for the candidate co-components support their homology in the twilight zone of rapidly evolving sequences and provide mechanistic hypotheses about previously unrecognized lipid-sensing functions.

Original languageEnglish (US)
Article numbere2203176119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 14 2022


  • co-component signal transduction system
  • enteric bacteria protein structure prediction
  • protein sequence evolution
  • virulence transcription regulation

ASJC Scopus subject areas

  • General


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