Recent findings about the Yersinia enterocolitica phage shock protein response

Abstract

The phage shock protein (Psp) system is a conserved extracytoplasmic stress response in bacteria that is essential for virulence of the human pathogen Yersinia enterocolitica. This article summarizes some recent findings about Y. enterocolitica Psp system function. Increased psp gene expression requires the transcription factor PspF, but under non-inducing conditions PspF is inhibited by an interaction with another protein, PspA, in the cytoplasm. A Psp-inducing stimulus causes PspA to relocate to the cytoplasmic membrane, freeing PspF to induce psp gene expression. This PspA relocation requires the integral cytoplasmic membrane proteins, PspB and PspC, which might sense an inducing trigger and sequester PspA by direct interaction. The subsequent induction of psp gene expression increases the PspA concentration, which also allows it to contact the membrane directly, perhaps for its physiological function. Mutational analysis of the PspB and PspC proteins has revealed that they both positively and negatively regulate psp gene expression and has also identified PspC domains associated with each function. We also compare the contrasting physiological roles of the Psp system in the virulence of Y. enterocolitica and Salmonella enterica sv. Typhimurium (S. Typhimurium). In S. Typhimurium, PspA maintains the proton motive force, which provides the energy needed to drive ion importers required for survival within macrophages. In contrast, in the extracellular pathogen Y. enterocolitica, PspB and PspC, but not PspA, are the Psp components needed for virulence. PspBC protect Y. enterocolitica from damage caused by the secretin component of its type 3 secretion system, an essential virulence factor.

Fig. 1. Model for activation of the Y. enterocolitica Psp system

In non-inducing conditions PspB and PspC are in an “off” state and PspA forms an inhibitory complex with PspF in the cytoplasm. Secretin mislocalization to the cytoplasmic membrane generates an inducing signal that switches PspB and PspC to their “on” state, allowing them to sequester PspA by protein-protein interaction. PspF becomes active, induces the pspA promoter, and the concentration of PspA, -B, and -C increases to the levels required for stress-relief and/or prevention. The increase in PspA concentration also compensates for a low phospholipid binding affinity, allowing it to bind to the membrane directly only after Psp system induction.

Fig. 2. Summary of the contrasting roles of the Psp system in supporting the virulence of Y. enterocolitica and S. enterica sv. Typhimurium (S. Typhimurium)

In the extracellular pathogen Y. enterocolitica (left) the Ysc T3SS must be produced during host infection to disarm the functions of host immune cells via the function of the exported Yop effector proteins. However, some of the YscC secretin component mislocalizes to the cytoplasmic membrane with the potential to compromise membrane integrity. Secretin mislocalization induces the Psp system and under these conditions the integral cytoplasmic membrane proteins PspB and PspC (but not PspA) are essential for Y. enterocolitica viability. It is not yet known how PspBC prevent or counteract secretin-toxicity. In the intracellular pathogen S. Typhimurium (right) the available divalent cation concentration within the macrophage phagosome is maintained at a low level by the action of the host Nramp1 protein. As a result, S. Typhimurium relies on proton (H+)-dependent and ATP-dependent (not shown) transporters to accumulate divalent cations (Me²⁺). In this situation, the role of PspA in maintaining the proton motive force is essential because it ensures an energy supply for metal ion import. How PspA achieves this function and the source of the Psp-inducing signal during host infection by S. Typhimurium is unknown.