Antiprotease inactivation by Salmonella enterica released from infected macrophages

Cell Microbiol 7: 529-538 (2005)

Speaker：楊朝傑                            Time：15:10~16:10, May 18, 2005

Commentator：何漣漪 老師                  Place：Room 601

Abstract：

Salmonella enterica serovar Typhimurium causes human gastroenteritis with symptoms of diarrhoea, fever and cramping.  Salmonella is a typical intracellular pathogen that could be multiply inside macrophages.  PgtE, a surface protease of S. enterica which has been known to activate the plasminogen to plasmin.¹  The mammalian plasminogen (Plg)–plasmin system has a central role in fibrinolysis and extracellular matrix degradation.  Numerous pathogenic bacterial species use the Plg system for migration across tissue barriers or for nutritional demands during infection.²  In this paper, the authors found that PgtE could inactivate α₂-antiplasmin (α₂AP) to enhance the plasminogen convert to plasmin.  However, α₂AP inactivation was only detected in S. enterica 10428R (the rough derivative of S. enterica 10428), but not in the smooth wild-type strain S. enterica 10428.  The authors suggest that the loss of LPS O-antigen in S. enterica 10428R might enhance PgtE contact with its substrate molecule.  When S. enterica 10428 infected to murine J774A.1 macrophage-like cells, they found the infected cells lysate and bacteria isolated from Salmonella-containing vacuoles (SCVs) could cleave α₂AP, but not bacteria incubated in Luria broth.  In addition, bacteria from SCVs produced an elevated level of PgtE and had a reduced O-antigen chain length.  These results suggest that the activity of PgtE is enhanced during growth of Salmonella inside macrophages and this promotes

degradation of host α₂AP by bacteria released from macrophages.³

References：

1.      Kukkonen, M. et al. Lack of O-antigen is essential for plasminogen activation by Yersinia pestis and Salmonella enterica. Mol Microbiol 51: 215-225 (2004).

2.      Lähteenmäki, K. et al. Bacterial metastasis: the host plasminogen system in bacterial invasion. Trends Microbiol 13:79-85 (2005).

3.      Lähteenmäki, K. et al. Antiprotease inactivation by Salmonella enterica released from infected macrophages. Cell Microbiol 7: 529-538 (2005).