Limiting too much of a good thing: a negative feedback mechanism prevents unregulated translocation of type III effector proteins.

Type III secretion systems (T3SS) are highly specialized structures termed injectisomes which function by translocating bacterial effector proteins via hollow needles directly into eukaryotic target cells. The translocated effectors alter target cell physiology to promote the pathogenic and symbiotic lifestyles of many gram-negative bacterial species. Orchestrating T3SS activity requires multiple levels of regulatory control to ensure appropriate timing of gene expression, needle complex assembly, pore formation in the target cell membrane, and translocation of the effectors into target cells. Most of the work thus far has focused on regulatory events leading up to and including translocation of the effectors. Although fewer studies have examined regulatory events that occur following translocation of the effectors into target cells, recent evidence indicates that translocation in Yersinia pseudotuberculosis is a regulated event that is controlled by the translocated YopE effector (1). In this issue of the Journal of Bacteriology, Cisz et al. demonstrate that a similar negative feedback mechanism operates in Pseudomonas aeruginosa (3). Using an elegant microscopy-based assay, they provide evidence that the autolimiting effect on translocation prevents subsequent bacteria from deploying the T3SS against the same target cell. In a separate line of investigation, they propose that host contact-mediated activation of translocation involves a shift in the substrate specificity of the injectisome and provide evidence that the signal associated with target cell contact is not the low-Ca2+ environment of the host cell cytoplasm.