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

Abstract

Significance Using the domain and operon organization of VtrA/VtrC, combined with fold predictions, we identify co-component signal transduction systems in enteric bacteria that likely regulate virulence. We observe that the heterodimeric VtrA/VtrC periplasmic bile acid receptor controlling the Vibrio parahaemolyticus type 3 secretion system 2 is a distant homolog of the ToxR/ToxS master regulator of virulence and has evolved beyond confident sequence recognition. Exploiting the newly developed machine learning methods for structure prediction, we observe a VtrC-like lipocalin fold for both the ToxS periplasmic domain and other detected periplasmic sensor components. This structure prediction supports the divergent evolution of VtrA/VtrC-like co-component signal transduction systems and suggests a role for lipid sensing in regulating virulence in enteric bacteria.