A Key Role for the Urokinase Plasminogen Activator (uPA) in Invasive Group A Streptococcal Infection.

Martina L. Sanderson-Smith, Yueling Zhang, Diane Ly, Deborah Donahue, Andrew Hollands, Victor Nizet, Marie Ranson, Victoria A. Ploplis, Mark J. Walker, Francis J. Castellino. PLoS Pathog.(2013) 9(7), e1003469.

Speaker: Po-Sheng Tsai (蔡伯昇)                  Time: 13:00~14:00, Oct. 30, 2013

Commentator: Dr. Shu-Ying Wang (王淑鶯老師)         Place: Room 601

Abstract

The ability of group A streptococcus (GAS) to activate and recruit host plasminogen is critical for initiating invasive disease (1). However, the mechanism of how GAS interacts with the hostfibrinolytic system is not fully elucidated. In this study, the authors investigated the role of a host activator of plasminogen, urokinase-type plasminogen activator (uPA), in invasive GAS infection (2, 3). The results of bacterial cell surface plasmin acquisition showed that the decrease of cell surface plasmin in absence of streptokinase (Ska), a bacterial plasminogen activator, was recovered by adding human uPA. Incubation of either WT or Ska-knockout mutant with plasma enhanced the generation of uPA. In vivo results showed that the survival rate of uPA^-/- mice were significantly higher than WT. Furthermore, to understand the interaction between Ska and human plasminogen in vivo, the authors crossed the humanized plasminogen mice with uPA^-/- mice, establishingAlbPLG1/uPA^-/- infection model. The mortality was significantly reduced in the absence of both uPA and Ska. In addition, bacterial counts in blood and spleen of AlbPLG1 and AlbPLG1/uPA^-/-mice showed that dissemination correlated with uPA mediated plasmin acquisition. In conclusion, the authors demonstrated that uPA mediated plasminogen activation and contributed to systemic GAS disease in AlbPLG1/uPA^-/- mice model.

References:

1.     Sanderson-Smith M, De Oliveira DP, Ranson M, McArthur JD. (2012) Bacterial plasminogen receptors: Mediators of a multifaceted relationship. Journal of Biomedicine and Biotechnology.2012, doi: 10.1155/2012/272148.

2.     Ellis V, Scully MF, Kakkar VV. (1989) Plasminogen activation initiated by singlechain urokinase-type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem. 264, 2185–2188.

3.     Winkler F, Kastenbauer S, Koedel U, Pfister HW. (2002) Role of the urokinase plasminogen activator system in patients with bacterial meningitis. Neurology. 59, 1350–1355.