Diversification of a Salmonella virulence protein function by ubiquitin-dependent differential localization

Jayesh C. Patel, et al. Cell. 137, 283-294 (2009)

Speaker：Shu-Chun Chien (簡淑珺)                                      Time：13:10~14:00, Dec.16, 2009

Commentator：Dr. Jiunn-Jong Wu (吳俊忠老師)          Place：Room 601

Abstract:

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a food-borne bacterial pathogen causing gastroenteritis in the human. S. Typhimurium manipulates many aspects of host cell physiology through translocating the effector proteins via the type III secretion system. One of the effector proteins, SopB, is a phosphoinositide phosphatase involved in diverse functions at different locations. Early in the infection of host cells, SopB is localized in the host plasma membrane by its C-terminal hydrophobic domain and regulates Akt activation, macropinocytosis, and actin remodeling to bring about bacterial internalization. SopB was then translocated from the host plasma membrane to Salmonella-containing vacuole (SCV) , where it is required for bacterial replication. In this study, the authors demonstrated that the SopB translocated to SCV was monoubiquitinated at multiple sites. The ubiquitination of SopB was not subjected to the degradation of this protein, because inhibition of protein synthesis did not result in a decrease of SopB in the translocation fraction. Instead, the ubiquitination of SopB is required for translocation to SCV, because a SopB mutant defective in ubiquitination (SopB^Dub) was not colocalized with SCV. In addition, SopB^Dub was found to remain on the plasma membrane after bacterial internalization and result in a concurrently prolonged macropinocytosis and Akt activation. Furthermore, this mutant could not recruit Rab5, which is required for SCV maturation, and thus caused reduced intracellular bacterial replication. These results suggest that, using the host cell ubiquitination machinery, SopB could diversify its function by localizing in different cellular compartments at different times during infection. Thus, S. Typhimurium can expend the virulence factor functions to amplify its capability to regulate the host cellular functions.

References:

1. Norris, F.A., et al. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc. Natl. Acad. Sci. USA 95, 14057–14059. (1998)

2. Rogers, L.D., et al. Identification of cognate host targets and specific ubiquitylation sites on the Salmonella SPI-1 effector SopB/SigD. J. Proteomics 71, 97-108 (2008)