Yersinia actively downregulates type III secretion and adhesion at higher cell densities

Abstract

The T3SS injectisome is used by Gram-negative bacteria, including important pathogens, to manipulate eukaryotic target cells by injecting effector proteins. While in some bacterial species, T3SS-negative bacteria benefit from the activity of their T3SS-positive siblings, the T3SS model organism Yersinia enterocolitica was thought to uniformly express and assemble injectisomes. In this study, we found that Yersinia actively suppress T3SS expression, assembly and activity at higher cell densities, such as inside microcolonies. This effect is highly specific to the T3SS, reversible, and distinct from stationary phase adaptation. It is conferred by the main T3SS transcription factor VirF, which is downregulated at higher densities and whose in trans expression restores T3SS activity. Transcript analysis showed that this effect is mediated by increased levels of the regulatory RNAs CsrBC, which sequester the regulatory protein CsrA and destabilize the virF transcript. The concomitant downregulation of the VirF-dependent adhesin YadA led to a drastic reduction in bacterial cell adhesion. We propose that this active suppression of T3SS secretion and cell attachment at higher local bacterial densities promotes a switch during Yersinia infection from a T3SS-active colonization stage to a bacterial replication and dissemination phase.