Y ersinia Ysc ‐ Yop type III secretion feedback inhibition is relieved through YscV ‐dependent recognition and secretion of LcrQ

Summary Human pathogenic Y ersinia species share a virulence plasmid encoding the Ysc ‐ Yop type III secretion system ( T 3 SS ). A plasmid‐encoded anti‐activator, LcrQ , negatively regulates the expression of this secretion system. Under inducible conditions, LcrQ is secreted outside of bacterial cells and this activates the T 3 SS , but the mechanism of targeting LcrQ for type III secretion remains largely unknown. In this study, we characterized the regulatory role of the export apparatus component YscV . Depletion or overexpression of YscV compromised Yop synthesis and this primarily prevented secretion of LcrQ . It followed that a lcrQ deletion reversed the repressive effects of excessive YscV . Further characterization demonstrated that the YscV residues 493–511 located within the C ‐terminal soluble cytoplasmic domain directly bound with LcrQ . Critically, YscV ‐ LcrQ complex formation was a requirement for LcrQ secretion, since YscV Δ493–511 failed to secrete LcrQ . This forced a cytoplasmic accumulation of LcrQ , which predictably caused the feedback inhibition of Yops synthesis. Based on these observations, we proposed a model for the YscV ‐dependent secretion of LcrQ and its role in regulating Yop synthesis in Y ersinia .