Increased Plasmid Copy-number is Essential for Yersinia T3SS Function and Virulence

Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacteria, Yersinia, utilizes a powerful Type III secretion virulence system (T3SS), encoded by a 70-kb, low-copy, IncFII-class virulence plasmid. Here, we report a novel virulence strategy in Y. pseudotuberculosis where this pathogen up-regulates the plasmid copy-number during infection. We show that increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we found direct, tight coupling between plasmid replication and T3SS function. This novel regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria.